Cancer Research and Treatment

Original Articles

Breast cancer

A Phase II Trial of S-1 and Oxaliplatin in Patients with Metastatic Breast Cancer Previously Treated with Anthracycline and Taxane (KCSG-BR07-03): Dae-Won Lee, Bhumsuk Keam, Keun Seok Lee, Jin-Hee Ahn, Joohyuk Sohn, Jin Seok Ahn, Moon Hee Lee, Jee Hyun Kim, Kyung Eun Lee, Hyo Jung Kim, Si-Young Kim, Yeon Hee Park, Chan-Young Ock, Kyung-Hun Lee, Sae-Won Han, Sung-Bae Kim, Young Hyuck Im, Hyun Cheol Chung, Do-Youn Oh, Seock-Ah Im; Cancer Res Treat. 2023;55(2):523-530. Published online November 8, 2022; DOI: https://doi.org/10.4143/crt.2022.1360

Purpose
This single-arm phase II trial investigate the efficacy and safety of S-1 plus oxaliplatin (SOX) in patients with metastatic breast cancer.
Materials and Methods
Patients with metastatic breast cancer previously treated with anthracyclines and taxanes were enrolled. Patients received S-1 (40-60 mg depending on patient’s body surface area, twice a day, day 1-14) and oxaliplatin (130 mg/m2, day 1) in 3 weeks cycle until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumor 1.1. Secondary endpoints included time-to-progression (TTP), duration-of-response (DoR), overall survival (OS), and adverse events.
Results
A total of 87 patients were enrolled from 11 institutions in Korea. Hormone receptor was positive in 54 (62.1%) patients and six (6.9%) had human epidermal growth factor receptor 2–positive disease. Forty-eight patients (85.1%) had visceral metastasis and 74 (55.2%) had more than three sites of metastases. The ORR of SOX regimen was 38.5% (95% confidence interval [CI], 26.9 to 50.0) with a median TTP of 6.0 months (95% CI, 5.1 to 6.9). Median DoR and OS were 10.3 months (95% CI, 5.5 to 15.1) and 19.4 (95% CI, not estimated) months, respectively. Grade 3 or 4 neutropenia was reported in 28 patients (32.1%) and thrombocytopenia was observed in 23 patients (26.6%).
Conclusion
This phase II study showed that SOX regimen is a reasonable option in metastatic breast cancer previously treated with anthracyclines and taxanes.

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Unraveling the immune landscape and therapeutic biomarker PMEPA1 for oxaliplatin resistance in colorectal cancer: A comprehensive approach
Zhengguang Zhang, Tianming Lu, Zhe Zhang, Zixian Liu, Ruoning Qian, Ruogu Qi, Fuqiong Zhou, Min Li
Biochemical Pharmacology.2024; 222: 116117. CrossRef
Efficacy and safety of utidelone plus capecitabine in advanced first-line therapy for metastatic breast cancer: A multicenter real-world study
Pingping Bi, Xi Wang, Rui Liu, Xiuqin Li, Shanrong Wei, Jiawen Zhao, Xin Tan, Fan Zhang, Qing Mao, Ying Zhang, Baoyan Tang, Xueqiong Xun, Rong Guo, Kai Zheng, Shaoqiang Zhou, Shicong Tang
Surgery Open Science.2023; 16: 171. CrossRef

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Gastrointestinal Cancer

Optimal Maintenance Strategy for First-Line Oxaliplatin-Containing Therapy with or without Bevacizumab in Patients with Metastatic Colorectal Cancer: A Meta-Analysis: Toshikazu Moriwaki, Masahiko Gosho, Akinori Sugaya, Takeshi Yamada, Yoshiyuki Yamamoto, Ichinosuke Hyodo; Cancer Res Treat. 2021;53(3):703-713. Published online December 1, 2020; DOI: https://doi.org/10.4143/crt.2020.805

Abstract PDF Supplementary Material PubReader ePub: Purpose
Maintenance therapy after oxaliplatin withdrawal is useful in patients with metastatic colorectal cancer (mCRC). This study aimed to investigate the timing of discontinuation or reintroduction of oxaliplatin and the optimal maintenance therapy regimen for survival.
Materials and Methods
PubMed and conference abstracts were searched to select phase II and III trials of first-line oxaliplatin-containing therapy with or without bevacizumab using maintenance therapy for mCRC. Correlations of median overall survival (OS) with induction therapy regimens, induction therapy duration, maintenance therapy regimens (fluoropyrimidine plus bevacizumab [FP+Bev], FP/Bev alone, and no treatment), and oxaliplatin reintroduction were investigated using correlation and weighted multivariate regression analyses.
Results
Twenty-two treatment arms were analyzed, including 2,581 patients. The maintenance therapy regimen FP+Bev showed the strongest correlation with a prolonged OS (Spearman’s partial correlation coefficient=0.42), and the other three variables correlated weakly with the OS. The maintenance therapy regimen significantly interacted with the induction chemotherapy duration (p=0.019). The predicted OS for FP+Bev crossed the lines of FP/Bev alone at 18 weeks of induction therapy, and of no treatment at 23 weeks. The corresponding OS at 12 and 27 weeks of induction therapies were 28.6 and 24.2 months for FP+Bev, 25.9 and 28.8 months for FP/Bev alone, and 20.5 and 27.5 months for no treatment.
Conclusion
The optimal maintenance therapy regimen for the OS is a continuous induction therapy as long as possible followed by FP/Bev alone and switching to FP+Bev within approximately 4 months if induction therapy is discontinued.

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Clinical Outcomes of Second-Line Chemotherapy after Progression on Nab-Paclitaxel Plus Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma: Kyoungmin Lee, Kyunghye Bang, Changhoon Yoo, Inhwan Hwang, Jae Ho Jeong, Heung-Moon Chang, Dongwook Oh, Tae Jun Song, Do Hyun Park, Sang Soo Lee, Sung Koo Lee, Myung-Hwan Kim, Jin-hong Park, Kyu-pyo Kim, Baek-Yeol Ryoo; Cancer Res Treat. 2020;52(1):254-262. Published online July 9, 2019; DOI: https://doi.org/10.4143/crt.2019.190

Abstract PDF Supplementary Material PubReader ePub

Purpose
Since the introduction of nab-paclitaxel plus gemcitabine (nab-P+GEM) as first-line (1L) treatment for metastatic pancreatic adenocarcinoma (mPDAC), optimal second-line (2L) chemotherapy after progression is unclear. We assessed clinical outcomes of 2L chemotherapy for disease that progressed on 1L nab-P+GEM.
Materials and Methods
Among the 203 patients previously treated with 1L nab-P+GEM for mPDAC at Asan Medical Center, between February and December 2016, records of 120 patients receiving 2L chemotherapy after progression on nab-P+GEM were retrospectively reviewed. The response rate and survival were evaluated along with analysis of prognostic factors.
Results
Fluoropyrimidine-oxaliplatin doublets (FOLFOX or XELOX) were used in 78 patients (65.0%), fluoropyrimidine monotherapy in 37 (30.8%), and liposomal irinotecan plus fluorouracil in two (1.7%). The median progression-free survival (PFS) and overall survival (OS) were 3.29 months and 7.33 months from the start of 2L therapy. Fluoropyrimidine-oxaliplatin regimens and fluoropyrimidine monotherapy did not yield significantly different median PFS (2.89 months vs. 3.81 months, p=0.40) or OS (7.04 months vs. 7.43 months, p=0.86). A high neutrophil-lymphocyte ratio (> 2.2) and a short time to progression with 1L nab-P+GEM (< 6.4 months) were independent prognostic factors of poor OS with 2L therapy.
Conclusion
2L fluoropyrimidine-oxaliplatin doublets and fluoropyrimidine monotherapy after failure of 1L nab-P+GEM had modest efficacy, with no differences in treatment outcomes between them. Further investigation is warranted for the optimal 2L chemo-regimens and sequencing of systemic chemotherapy for patients with mPDAC.

Citations

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Effect of a MUC5AC Antibody (NPC-1C) Administered With Second-Line Gemcitabine and Nab-Paclitaxel on the Survival of Patients With Advanced Pancreatic Ductal Adenocarcinoma
Brandon M. Huffman, Atrayee Basu Mallick, Nora K. Horick, Andrea Wang-Gillam, Peter Joel Hosein, Michael A. Morse, Muhammad Shaalan Beg, Janet E. Murphy, Sharon Mavroukakis, Anjum Zaki, Benjamin L. Schlechter, Hanna Sanoff, Christopher Manz, Brian M. Wolp
JAMA Network Open.2023; 6(1): e2249720. CrossRef
Trend Analysis and Prediction of Hepatobiliary Pancreatic Cancer Incidence and Mortality in Korea
Hyeong Min Park, Young-Joo Won, Mee Joo Kang, Sang-Jae Park, Sun-Whe Kim, Kyu-Won Jung, Sung-Sik Han
Journal of Korean Medical Science.2022;[Epub] CrossRef
EUS-guided ablation with the HybridTherm Probe as second-line treatment in patients with locally advanced pancreatic ductal adenocarcinoma: A case–control study
Sabrina Gloria Giulia Testoni, Maria Chiara Petrone, Michele Reni, Clelia Di Serio, Paola Maria Rancoita, Gemma Rossi, Gianpaolo Balzano, Walter Linzenbold, Markus Enderle, Emanuel Della-Torre, Francesco De Cobelli, Massimo Falconi, Gabriele Capurso, Paol
Endoscopic Ultrasound.2022; 11(5): 383. CrossRef
Phase II clinical trial of nab-paclitaxel plus gemcitabine in elderly patients with previously untreated locally advanced or metastatic pancreatic adenocarcinoma: the BIBABRAX study
Jaime Feliu, Mónica Jorge Fernández, Teresa Macarulla, Bartomeu Massuti, Ana Albero, José Federico González González, Guillermo Quintero-Aldana, Juan Ignacio Delgado-Mingorance, Ana Fernández Montes, Carmen García Piernavieja, Manuel Valladares-Ayerbes, A
Cancer Chemotherapy and Pharmacology.2021; 87(4): 543. CrossRef
Liposomal irinotecan plus fluorouracil/leucovorin versus FOLFIRINOX as the second-line chemotherapy for patients with metastatic pancreatic cancer: a multicenter retrospective study of the Korean Cancer Study Group (KCSG)
H.S. Park, B. Kang, H.J. Chon, H.-S. Im, C.-K. Lee, I. Kim, M.J. Kang, J.E. Hwang, W.K. Bae, J. Cheon, J.O. Park, J.Y. Hong, J.H. Kang, J.H. Kim, S.H. Lim, J.W. Kim, J.-W. Kim, C. Yoo, H.J. Choi
ESMO Open.2021; 6(2): 100049. CrossRef
Pancreatic adenocarcinoma: Beyond first line, where are we?
Sara Cherri, Silvia Noventa, Alberto Zaniboni
World Journal of Gastroenterology.2021; 27(17): 1847. CrossRef
Evolution of Systemic Therapy in Metastatic Pancreatic Ductal Adenocarcinoma
Mandana Kamgar, Sakti Chakrabarti, Aditya Shreenivas, Ben George
Surgical Oncology Clinics of North America.2021; 30(4): 673. CrossRef
Treatment optimization of locally advanced and metastatic pancreatic cancer (Review)
Anabela Barros, Catarina Pulido, Manuela Machado, Maria Brito, Nuno Couto, Olga Sousa, Sónia Melo, Hélder Mansinho
International Journal of Oncology.2021;[Epub] CrossRef
Real World Evidence on Second-Line Palliative Chemotherapy in Advanced Pancreatic Cancer
Emma Gränsmark, Nellie Bågenholm Bylin, Hakon Blomstrand, Mats Fredrikson, Elisabeth Åvall-Lundqvist, Nils O. Elander
Frontiers in Oncology.2020;[Epub] CrossRef
FOLFIRINOX after first-line gemcitabine-based chemotherapy in advanced pancreatic cancer: a retrospective comparison with FOLFOX and FOLFIRI schedules
Francesca Foschini, Fabiana Napolitano, Alberto Servetto, Roberta Marciano, Eleonora Mozzillo, Anna Chiara Carratù, Antonio Santaniello, Pietro De Placido, Priscilla Cascetta, Giovanni Butturini, Isabella Frigerio, Paolo Regi, Nicola Silvestris, Sabina De
Therapeutic Advances in Medical Oncology.2020;[Epub] CrossRef
Laparoscopic repeated pancreatectomy for isolated local recurrence in remnant pancreas following laparoscopic radical pancreatectomy for pancreatic ductal adenocarcinoma: Two cases report
Munseok Choi, Suk Jun Lee, Dong-Min Shin, Ho Kyoung Hwang, Woo Jung Lee, Chang Moo Kang
Annals of Hepato-Biliary-Pancreatic Surgery.2020; 24(4): 542. CrossRef
Possibilities of palliative chemotherapy in patients with locally advanced and metastatic pancreatic cancer
L. I. Moskvicheva, L. V. Bolotina
Research and Practical Medicine Journal.2020; 7(4): 118. CrossRef

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Multicenter Phase II Study of Oxaliplatin, Irinotecan, and S-1 as First-line Treatment for Patients with Recurrent or Metastatic Biliary Tract Cancer: Changhoon Yoo, Boram Han, Hyeong Su Kim, Kyu-pyo Kim, Deokhoon Kim, Jae Ho Jeong, Jae-Lyun Lee, Tae Won Kim, Jung Han Kim, Dae Ro Choi, Hong Il Ha, Jinwon Seo, Heung-Moon Chang, Baek-Yeol Ryoo, Dae Young Zang; Cancer Res Treat. 2018;50(4):1324-1330. Published online January 8, 2018; DOI: https://doi.org/10.4143/crt.2017.526

Abstract PDF Supplementary Material PubReader ePub

Purpose
Although gemcitabine plus cisplatin has been established as the standard first-line chemotherapy for patients with advanced biliary tract cancer (BTC), overall prognosis remains poor. We investigated the efficacy of a novel triplet combination of oxaliplatin, irinotecan, and S-1 (OIS) for advanced BTC.
Materials and Methods
Chemotherapy-naive patientswith histologically documented unresectable or metastatic BTC were eligible for this multicenter, single-arm phase II study. Patients received 65 mg/m² oxaliplatin (day 1), 135 mg/m² irinotecan (day 1), and 40 mg/m² S-1 (twice a day, days 1-7) every 2 weeks. Primary endpoint was objective response rate. Targeted exome sequencing for biomarker analysis was performed using archival tissue.
Results
In total, 32 patients were enrolled between October 2015 and June 2016. Median age was 64 years (range, 40 to 76 years), with 24 (75%) male patients; 97% patients had metastatic or recurrent disease. Response rate was 50%, and median progression-free survival and overall survival (OS) were 6.8 months (95% confidence interval [CI], 4.8 to 8.8) and 12.5 months (95% CI, 7.0 to 18.0), respectively. The most common grade 3-4 adverse events were neutropenia (32%), diarrhea (6%), and peripheral neuropathy (6%). TP53 and KRAS mutations were the most frequent genomic alterations (42% and 32%, respectively), and KRAS mutations showed a marginal relationship with worse OS (p=0.07).
Conclusion
OIS combination chemotherapy was feasible and associated with favorable efficacy outcomes as a first-line treatment in patients with advanced BTC. Randomized studies are needed to compare OIS with gemcitabine plus cisplatin.

Citations

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A phase 1 study of biweekly nab-paclitaxel/oxaliplatin/S-1/LV for advanced upper gastrointestinal cancers: TCOG T1216 study
Hui-Jen Tsai, Shih-Hung Yang, Chin-Fu Hsiao, Hsiang-Fong Kao, Yung-Yeh Su, Yan-Shen Shan, Chia-Jui Yen, Jeng-Shiun Du, Chiun Hsu, I-Chen Wu, Li-Tzong Chen
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Liposomal irinotecan, oxaliplatin, and S-1 as first-line therapy for patients with locally advanced or metastatic pancreatic adenocarcinoma (NASOX): A multicenter phase I/IIa study
Hyehyun Jeong, Bum Jun Kim, Choong-kun Lee, Inkeun Park, Dae Young Zang, Hye Jin Choi, Sang Soo Lee, Do Hyun Park, Tae Jun Song, Dongwook Oh, Sung-Hoon Moon, Kyu-pyo Kim, Zev Wainberg, Baek-Yeol Ryoo, Changhoon Yoo
European Journal of Cancer.2024; 208: 114194. CrossRef
Redox-responsive engineered hybrid nanomedicine for gallbladder cancer therapy via hyaluronic acid depletion
Jinglin Zou, Cong Jiang, Xianglong Li, Tianyu Zhong, Shuqi Wang, Bo Wang, Dapeng Zhang, Ji-Na Hao, Yuanyuan Cao, Mengjia Guan, Peng Zhang, Bin Dai, Yongsheng Li
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Cindy Neuzillet, Pascal Artru, Eric Assenat, Julien Edeline, Xavier Adhoute, Jean-Christophe Sabourin, Anthony Turpin, Romain Coriat, David Malka
Targeted Oncology.2023; 18(1): 51. CrossRef
Neoadjuvant Therapy for Extrahepatic Biliary Tract Cancer: A Propensity Score-Matched Survival Analysis
Junya Toyoda, Kota Sahara, Tomoaki Takahashi, Kentaro Miyake, Yasuhiro Yabushita, Yu Sawada, Yuki Homma, Ryusei Matsuyama, Itaru Endo, Timothy Pawlik
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Modified FOLFIRINOX Versus CISGEM Chemotherapy for Patients With Advanced Biliary Tract Cancer (PRODIGE 38 AMEBICA): A Randomized Phase II Study
Jean marc Phelip, Jérôme Desrame, Julien Edeline, Emilie Barbier, Eric Terrebonne, Pierre Michel, Hervé Perrier, Laetitia Dahan, Vincent Bourgeois, Faiza Khemissa Akouz, Emilie Soularue, Valérie Lebrun Ly, Yann Molin, Thierry Lecomte, François Ghiringhell
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Early Recurrence in Resected Gallbladder Carcinoma: Clinical Impact and Its Preoperative Predictive Score
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Efficacy and safety of modified FOLFIRINOX as salvage therapy for patients with refractory advanced biliary tract cancer: a retrospective study
Liu-Fang Ye, Chao Ren, Long Bai, Jie-Ying Liang, Ming-Tao Hu, Hui Yang, Zhi-Qiang Wang, Feng-Hua Wang, Rui-Hua Xu, Yu-Hong Li, De-Shen Wang
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Alexander A. Azizi, Angela Lamarca, Mairéad G. McNamara, Juan W. Valle
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Changhoon Yoo, Kyu-pyo Kim, Jae Ho Jeong, Ilhwan Kim, Myoung Joo Kang, Jaekyung Cheon, Byung Woog Kang, Hyewon Ryu, Ji Sung Lee, Kyung Won Kim, Ghassan K Abou-Alfa, Baek-Yeol Ryoo
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Efficacy of Chemotherapy in Patients with Unresectable or Metastatic Pancreatic Acinar Cell Carcinoma: Potentially Improved Efficacy with Oxaliplatin-Containing Regimen: Changhoon Yoo, Bum Jun Kim, Kyu-pyo Kim, Jae-Lyun Lee, Tae Won Kim, Baek-Yeol Ryoo, Heung-Moon Chang; Cancer Res Treat. 2017;49(3):759-765. Published online November 9, 2016; DOI: https://doi.org/10.4143/crt.2016.371

Abstract PDF Supplementary Material PubReader ePub

Purpose
Pancreatic acinar cell carcinoma (ACC) is a rare cancer of the exocrine pancreas. Because of its rare incidence, the efficacy of chemotherapy in this patient population has been largely unknown. Therefore, we retrospectively analyzed the outcomes of patients with advanced pancreatic ACC who received chemotherapy.
Materials and Methods
Between January 1997 and March 2015, 15 patients with unresectable or metastatic pancreatic ACC who received systemic chemotherapy were identified in Asan Medical Center, Korea.
Results
The median age was 58 years. Eleven and four patients had recurrent/metastatic and locally advanced unresectable disease. The median overall survival in all patients was 20.9 months (95% confidence interval [CI], 15.7 to 26.1). As first-line therapy, intravenous 5-fluorouracil were administered in four patients (27%), gemcitabine in five (33%), gemcitabine plus capecitabine in two (13%), oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX) in two (13%), and concurrent chemoradiotherapy followed by capecitabine maintenance therapy in two (13%). The objective response rate (ORR) to chemotherapy alone was 23% and the median progression-free survival (PFS) was 5.6 months (95% CI, 2.8 to 8.4). After progression, second- line chemotherapy was administered in eight patients, while four patients received FOLFOX and the other four patients received gemcitabine. The ORR was 38%, and patients administered FOLFOX had significantly better PFS than those administered gemcitabine (median, 6.5 months vs. 1.4 months; p=0.007). The ratio of time to tumor progression (TTP) during first-line chemotherapy to TTP at second-line chemotherapy was significantly higher in patients administered FOLFOX (4.07; range, 0.87 to 8.30) than in those administered gemcitabine (0.12; range, 0.08 to 0.25; p=0.029).
Conclusion
Our results suggest that oxaliplatin-containing regimens may have improved activity against pancreatic ACC.

Citations

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Optimizing Chemotherapy of Pancreatic Acinar Cell Carcinoma: Our Experiences and Pooled Analysis of Literature
Jian-Ying Xu, Wen-Long Guan, Shi-Xun Lu, Xiao-Li Wei, Wen-Jie Shi, Chao Ren, Yu-Hong Li, Sheng-Ping Li, Miao-Zhen Qiu, Feng-Hua Wang
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Case Reports

Oxaliplatin-Induced Immune-Mediated Thrombocytopenia: A Case Report: Hyun Sun Woo, Kyoung Hwa Lee, Phill Hoon Yoon, Su Ji Kim, Inkeun Park, Young Saing Kim, Hee Kyung Ahn, Junshik Hong, Dong Bok Shin, Sun Jin Sym; Cancer Res Treat. 2015;47(4):949-953. Published online October 28, 2014; DOI: https://doi.org/10.4143/crt.2014.052

Abstract PDF PubReader ePub

Oxaliplatin is a third-generation platinum derivative used for metastatic or advanced colorectal cancer treatment. Although myelosuppression is the most common cause of oxaliplatin-induced thrombocytopenia, rare cases of oxaliplatin-induced immunemediated thrombocytopenia are reported. We report a case of a 57-year-old woman with colon cancer who developed gum bleeding and petechiae after oxaliplatin infusion. Laboratory tests revealed grade 4 thrombocytopenia and grade 4 neutropenia. She recovered from the thrombocytopenia and accompanying neutropenia within 4 days with no recurrence following discontinuation of oxaliplatin. Physicians need to be aware of the risk of severe acute thrombocytopenia following oxaliplatin administration.

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Risk Factors of Chemotherapy-Induced Thrombocytopenia After Oxaliplatin-Containing Chemotherapy for Gastrointestinal Malignancies
Ju Li, Wanqing Wang, Kaipeng Jiang, Jiuwei Cui, Chang Wang, Tingting Liang, Yizhuo Wang, Shuhan Liu, Wenshuo Zhou
Journal of Gastrointestinal Cancer.2024; 55(3): 1144. CrossRef
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Tumor Lysis Syndrome in a Patient with Metastatic Colon Cancer after Treatment with 5-Fluorouracil/Leucovorin and Oxaliplatin: Case Report and Literature Review: Hyung Duk Kim, Kyung Sun Ha, In Sook Woo, Yun Hwa Jung, Chi Wha Han, Tae-Jung Kim; Cancer Res Treat. 2014;46(2):204-207. Published online April 15, 2014; DOI: https://doi.org/10.4143/crt.2014.46.2.204

Abstract PDF PubReader ePub

Development of tumor lysis syndrome (TLS) may occur after chemotherapy or spontaneously in bulky or rapidly growing tumors. This syndrome is frequent but preventable in patients with hematologic malignancies. TLS following therapy has been reported infrequently in various types of solid tumors. TLS associated with oxaliplatin containing chemotherapy in a solid tumor has never been reported. A 59-year-old man received 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy for metastatic colon cancer. Development of TLS occurred three days after administration of chemotherapy. Two days later, his abnormal laboratory findings were recovered with appropriate management. To the best of our knowledge, the current case is the first report on development of acute TLS following oxaliplatin containing chemotherapy in a patient with colon cancer. We also review the literature on tumor lysis syndrome in patients with colorectal cancer.

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Oxaliplatin-associated shock in stage III colorectal cancer patients: real-world evidence in Taiwan
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Tumor Lysis Syndrome in Patients With Solid Tumors: A Systematic Review of Reported Cases
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Fluorouracil/folinic acid/oxaliplatin

Reactions Weekly.2014; 1505(1): 17. CrossRef

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Original Articles

Combination of TRAP1 and ERCC1 Expression Predicts Clinical Outcomes in Metastatic Colorectal Cancer Treated with Oxaliplatin/5-Fluorouracil: Jae Joon Han, Sun Kyung Baek, Jae Jin Lee, Gou Young Kim, Si-Young Kim, Suk-Hwan Lee; Cancer Res Treat. 2014;46(1):55-64. Published online January 15, 2014; DOI: https://doi.org/10.4143/crt.2014.46.1.55

Abstract PDF PubReader ePub

PURPOSE
The novel heat shock protein tumor necrosis factor receptor-associated protein 1 (TRAP1) is associated with multidrug resistance in colorectal cancer (CRC) cells in vitro. Excision repair cross-complementation group 1 (ERCC1) expression levels in tumor tissues also predict clinical outcomes in metastatic CRC patients receiving combination oxaliplatin and 5-fluorouracil treatment. We investigated whether TRAP1 and ERCC1 protein expression by immunohistochemistry predict clinical outcomes in CRC patients.
MATERIALS AND METHODS
The study population consisted of 56 patients with metastatic CRC who received first-line oxaliplatin/5-fluorouracil therapy. Clinical response and overall survival (OS) by levels of the markers TRAP1 and ERCC1 were evaluated.
RESULTS
The rates of TRAP1 and ERCC1 expression were 21% and 52%, respectively. Patients negative for ERCC1 expression showed a tendency to respond to chemotherapy (p=0.066). Median OS was significantly longer in patients negative for TRAP1 than those positive for TRAP1 (p=0.023). Patients negative for ERCC1 expression also had a better OS than those positive for ERCC1 (p=0.021). The median OS was 30.9 months for patients negative for TRAP1 and ERCC1 compared to 13.2 months for those positive for TRAP1 and/or positive for ERCC1 expression (p=0.006). The combination of TRAP1 and ERCC1 expression was significantly associated with the response to chemotherapy (p=0.046) and independently predicted median OS in multivariate analysis (hazard ratio, 2.98; 95% confidence interval, 1.18 to 7.49).
CONCLUSION
The present study demonstrates that the combination of TRAP1 and ERCC1 expression predicts the survival of metastatic CRC patients who were treated with oxaliplatin/5-fluorouracil.

Citations

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New insights into molecular chaperone TRAP1 as a feasible target for future cancer treatments
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Gene Copy Number and Post-Transductional Mechanisms Regulate TRAP1 Expression in Human Colorectal Carcinomas
Michele Pietrafesa, Francesca Maddalena, Luciana Possidente, Valentina Condelli, Pietro Zoppoli, Valeria Li Bergolis, Maria Grazia Rodriquenz, Michele Aieta, Giulia Vita, Franca Esposito, Matteo Landriscina
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HSPA1A, HSPA1L and TRAP1 heat shock genes may be associated with prognosis in ovarian epithelial cancer
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Gustavo A. Laporte, Natalia M. Leguisamo, Antonio N. Kalil, Jenifer Saffi
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Expression of DDB2 Protein in the Initiation, Progression, and Prognosis of Colorectal Cancer
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Thymidylate synthase expression in primary colorectal cancer as a predictive marker for the response to 5‑fluorouracil‑ and oxaliplatin‑based preoperative chemotherapy for liver metastases
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TRAP1: a viable therapeutic target for future cancer treatments?
Giacomo Lettini, Francesca Maddalena, Lorenza Sisinni, Valentina Condelli, Danilo Swann Matassa, Maria Paola Costi, Daniele Simoni, Franca Esposito, Matteo Landriscina
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TRAP1 protein signature predicts outcome in human metastatic colorectal carcinoma
Francesca Maddalena, Vittorio Simeon, Giulia Vita, Annamaria Bochicchio, Luciana Possidente, Lorenza Sisinni, Giacomo Lettini, Valentina Condelli, Danilo Swann Matassa, Valeria Li Bergolis, Alberto Fersini, Sante Romito, Michele Aieta, Antonio Ambrosi, Fr
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Elisabeth J Kap, Odilia Popanda, Jenny Chang-Claude
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TRAP1 regulates cell cycle and apoptosis in thyroid carcinoma cells
Giuseppe Palladino, Tiziana Notarangelo, Giuseppe Pannone, Annamaria Piscazzi, Olga Lamacchia, Lorenza Sisinni, Girolamo Spagnoletti, Paolo Toti, Angela Santoro, Giovanni Storto, Pantaleo Bufo, Mauro Cignarelli, Franca Esposito, Matteo Landriscina
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TRAP1 regulates stemness through Wnt/β-catenin pathway in human colorectal carcinoma
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TRAP1 downregulation in human ovarian cancer enhances invasion and epithelial–mesenchymal transition
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TRAP1 revisited: Novel localizations and functions of a ‘next-generation’ biomarker (Review)
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Feasibility of Oxaliplatin, Leucovorin, and 5-Fluorouracil (FOLFOX-4) Chemotherapy in Heavily Pretreated Patients with Recurrent Epithelial Ovarian Cancer: Hee Jun Lee, Hee Seung Kim, Noh Hyun Park, Hyun Hoon Chung, Jae Weon Kim, Yong Sang Song; Cancer Res Treat. 2013;45(1):40-47. Published online March 31, 2013; DOI: https://doi.org/10.4143/crt.2013.45.1.40

Abstract PDF PubReader ePub

PURPOSE
The purpose of this study is to evaluate the efficacy and toxicity of oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX-4) chemotherapy in heavily pretreated patients with recurrent epithelial ovarian cancer (EOC).
MATERIALS AND METHODS
Clinical data were reviewed in 28 patients who received FOLFOX-4 as more than the second-line chemotherapy, consisting of 85 mg/m2 of oxaliplatin as a 2-hour infusion, 200 mg/m2 of leucovorin as a 2-hour infusion, and bolus 400 mg/m2 on day 1, followed by a 22-hour infusion of 600 mg/m2 of 5-fluorouracil for two consecutive days every three weeks. In addition, its efficacy and toxicity were compared with those reported in in three previous relevant studies.
RESULTS
A total of 128 cycles of FOLFOX-4 were administered with the median number of five cycles (range, 1 to 10 cycles). In nine patients with measurable disease, complete response (CR) and partial response (PR) were observed in 0 (0%) and two (22.2%) patients, whereas in 19 patients with non-measurable disease, CR and PR were observed in 0 (0%) and five (26.3%) patients. Among all patients, grade 3 anemia, neutropenia, and thrombocytopenia were observed in two (7.1%), three (10.7%), and one (3.6%) patient, and grade 3 fatigue, nausea and vomiting, and peripheral neuropathy were observed in one (3.6%), two (7.1%), and three (10.7%) patients. In addition, median values of time to progressive disease and chemotherapy-specific survival were three months (range, 0 to 10 months) and nine months (range, 4 to 24 months).
CONCLUSION
FOLFOX-4 is feasible as salvage chemotherapy with acceptable toxicity for heavily pretreated patients with recurrent EOC.

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Outcomes of Third-Line Docetaxel-Based Chemotherapy in Advanced Gastric Cancer Who Failed Previous Oxaliplatin-Based and Irinotecan-Based Chemotherapies: Min Jeong Lee, In Gyu Hwang, Joung-Soon Jang, Jin Hwa Choi, Byeong-Bae Park, Myung Hee Chang, Seung Tae Kim, Se Hoon Park, Myoung Hee Kang, Jung Hun Kang; Cancer Res Treat. 2012;44(4):235-241. Published online December 31, 2012; DOI: https://doi.org/10.4143/crt.2012.44.4.235

Abstract PDF PubReader ePub

PURPOSE
Little is known about outcomes in the use of third-line chemotherapy in cases of advanced gastric cancer (AGC). The primary aim of this retrospective study was to evaluate outcomes of docetaxel-based chemotherapy in patients with AGC that progressed after both oxaliplatin-based and irinotecan-based regimens.
MATERIALS AND METHODS
Eligible patients were those with AGC who had previous chemotherapy including fluoropyrimidine and oxaliplatin as well as fluoropyrimidine and irinotecan and who received subsequent docetaxel-based chemotherapy. Thirty-five patients were retrospectively recruited from 5 medical centers in Korea. Patients received either weekly or 3 weekly with docetaxel +/- cisplatin.
RESULTS
Thirty-one out of 35 patients were evaluated for treatment response. A total of 94 cycles of chemotherapy (median, 2; range, 1 to 7) were administered. The overall response rate was 14.3%, and the disease control rate was 45.7%. The median progression-free survival (PFS) was 1.9 months (95% confidence interval [CI], 1.1 to 2.7 months). The median overall survival (OS) was 3.6 months (95% CI, 2.8 to 4.4 months). PFS and OS were significantly prolonged in patients of the Eastern Cooperative Oncology Group, with performance status of 0 or 1 in multivariate analysis (PFS: hazard ratio[HR], 0.411; 95% CI, 0.195 to 0.868; p=0.020 and OS: HR, 0.390; 95% CI, 0.184 to 0.826; p=0.014, respectively). Four of the 35 patients enrolled in the study died due to infection associated with neutropenia.
CONCLUSION
Our findings suggest that salvage docetaxel-based chemotherapy is a feasible treatment option for AGC patients with good performance status (PS), whereas chemotherapy for patients with poor PS (PS< or =2) should be undertaken with caution for those who previously failed oxaliplatin- and irinotecan-based regimens.

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HTA and Gastric Cancer: Evaluating Alternatives in Third- and Fourth-Line Patients
Lucrezia Ferrario, Federica Asperti, Giuseppe Aprile, Jacopo Giuliani
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Korean Practice Guidelines for Gastric Cancer 2022: An Evidence-based, Multidisciplinary Approach
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Current therapeutic options for gastric adenocarcinoma
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Prognostic Factors of Second and Third Line Chemotherapy Using 5-FU with Platinum, Irinotecan, and Taxane for Advanced Gastric Cancer: Ji Soo Park, Jae Yun Lim, Seung Kyo Park, Min Kyung Kim, Hee Sung Ko, Sun Och Yoon, Jong Won Kim, Seung Ho Choi, Jae Yong Cho; Cancer Res Treat. 2011;43(4):236-243. Published online December 27, 2011; DOI: https://doi.org/10.4143/crt.2011.43.4.236

Abstract PDF PubReader ePub

PURPOSE
The aims of this study are to find out whether the sequence of chemotherapeutic regimens including second- and third-line taxane and irinotecan influences the survival of patients with unresectable gastric carcinoma and to identify clinical characteristics of patients with improved response.
MATERIALS AND METHODS
Fifty gastric carcinoma patients who were treated by third-line sequential chemotherapy between November 2004 and July 2010 were enrolled in this study. Their overall survival (OS) and time to progression (TTP) were set up as primary and secondary end points. For the sequence of chemotherapy regimen, two arms were used. Arm A was defined as 5-fluorouracil (5-FU)+cisplatin (FP) or folinic acid, 5-FU and oxaliplati (FOLFOX), followed by folinic acid, 5-FU and irinotecan (FOLFIRI), and paclitaxel or docetaxel plus 5-FU, with or without epirubicin. Arm B was defined as FP or FOLFOX, followed by paclitaxel or docetaxel plus 5-FU, and FOLFIRI.
RESULTS
The median OS of all patients was 16.0 months (95% confidence interval, 13.6 to 18.3 months), which is longer than historical control of patients who did not receive third-line chemotherapy. The sequence of second and third-line regimen, including irinotecan and taxane, did not present significant difference in OS or TTP after failure of 5-FU with platinum chemotherapy. In survival analysis of patients' clinicopathologic characteristics, poor prognosis was shown in patients with poorly differentiated histologic features, elevated serum carcinoembryonic level, and shorter TTP of first line chemotherapy.
CONCLUSION
It is possible for patients to respond differently to chemotherapy due to differences in clinical features and underlying gene expression profiles. Development of individualized chemotherapy regimens based on gene expression profiles is warranted.

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Cancer Discovery.2021; 11(2): 308. CrossRef
Inhibiting casein kinase 2 overcomes paclitaxel resistance in gastric cancer
Minkyu Jung, Kyu Hyun Park, Hyun Myong Kim, Tae Soo Kim, Xianglan Zhang, Sun-Mi Park, Seung-Hoon Beom, Hyo Song Kim, Jae-Ho Cheong, Hyun Cheol Chung, John Soong, Shu-chuan Lin, Sun Young Rha
Gastric Cancer.2019; 22(6): 1153. CrossRef
Advanced gastric cancer: is there an optimal chemotherapy regimen?
Kalliopi Andrikou, Massimiliano Salati, Annalisa Fontana, Andrea Spallanzani, Stefania Pipitone, Fabio Gelsomino, Monica Barbolini, Stefano Cascinu
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Yu Zheng, Xu-Qing Zhu, Xiao-Gang Ren
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Mohammad Waseem, Upasana Sahu, Mohd. Salman, Arnab Choudhury, Sudeshna Kar, Heena Tabassum, Suhel Parvez, Saeid Ghavami
PLOS ONE.2017; 12(7): e0180953. CrossRef
Outcomes of Advanced Gastric Cancer Patients Treated with at Least Three Lines of Systemic Chemotherapy
Valentina Fanotto, Mario Uccello, Irene Pecora, Lorenza Rimassa, Francesco Leone, Gerardo Rosati, Daniele Santini, Riccardo Giampieri, Samantha Di Donato, Gianluca Tomasello, Nicola Silvestris, Filippo Pietrantonio, Francesca Battaglin, Antonio Avallone,
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Oncotarget.2017; 8(17): 29346. CrossRef
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Efficacy and Safety of Oxaliplatin, 5-Fluorouracil, and Folinic Acid Combination Chemotherapy as First-Line Treatment in Metastatic or Recurrent Gastric Cancer: Han Jo Kim, Jun Young Eun, Young Woo Jeon, Jina Yun, Kyoung Ha Kim, Se Hyung Kim, Hyun Jung Kim, Sang-Cheol Lee, Sang Byung Bae, Chan Kyu Kim, Nam Su Lee, Kyu Taek Lee, Seong-Kyu Park, Jong-Ho Won, Dae Sik Hong, Hee Sook Park; Cancer Res Treat. 2011;43(3):154-159. Published online September 30, 2011; DOI: https://doi.org/10.4143/crt.2011.43.3.154

Abstract PDF PubReader ePub

PURPOSE
We retrospectively determined the efficacy and safety of the combination of oxaliplatin, 5-fluorouracil (5-FU), and folinic acid (FA) as first-line chemotherapy for patients with metastatic or recurrent gastric cancer.
MATERIALS AND METHODS
Between January 2006 and August 2009, 39 patients with histologically-confirmed, metastatic or recurrent gastric cancer underwent chemotherapy, and the results were retrospectively investigated. The chemotherapy regimen consisted of oxaliplatin (100 mg/m2) and FA (200 mg/m2; 2-hour infusion), then 5-FU (2,400 mg/m2; 46-hour continuous infusion) every 2 weeks.
RESULTS
Thirty-nine patients received a total of 210 treatment cycles. The median number of cycles was 6 (range, 1 to 16). Of the 32 evaluable patients, zero patients achieved a complete response and 11 patients achieved a partial response (response rate, 28.2%). The median time-to-progression and overall survival were 4.3 months (95% confidence interval [CI], 2.0 to 6.5 months) and 9.8 months (95% CI, 3.5 to 16.0 months), respectively. The main hematologic toxicity was anemia, which was observed in 119 cycles (56.7%). Grade 3/4 neutropenia was observed in 32 cycles (15.2%). The main non-hematologic toxicity was constipation, which was observed in 91 cycles (46.2%). Peripheral neuropathy occurred in 71 cycles (33.8%); all cases were grade 1 or 2. No treatment-related deaths were reported.
CONCLUSION
This study showed that combination chemotherapy with oxaliplatin, 5-FU, and FA is an active and well-tolerated regimen as first-line treatment in patients with metastatic or recurrent gastric cancer.

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Post-Marketing Surveillance of a generic Oxaliplatin (AlvoxalⓇ) in Iranian Patients with Cancer
Farhad Shahi, Mojtaba Gorji, Mehrdad Payandeh, Hamid Rezvani, Mohammad Vaezi, Sharareh Seifi, Alireza Baari, Reza Khalili-Dizaji, Seyed Mehdi Hashemi, Saeid Salimi, Hosein Kamranzadeh, Babak Shazad, Sina Salari, Davoud Oulad Dameshghi, Mehdi Sarkheil, Meh
Current Therapeutic Research.2022; 96: 100657. CrossRef
Quantitative proteomic analysis of oxaliplatin induced peripheral neurotoxicity
Linlin Yang, Hua Wang, Wanting Lu, Gangqi Yang, Zian Lin, Ruibing Chen, Hongyan Li
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Current therapeutic options for gastric adenocarcinoma
C.R. Akshatha, Smitha Bhat, R. Sindhu, Dharini Shashank, Sarana Rose Sommano, Wanaporn Tapingkae, Ratchadawan Cheewangkoon, Shashanka K. Prasad
Saudi Journal of Biological Sciences.2021; 28(9): 5371. CrossRef
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H Liu, J Lu, Y Hua, P Zhang, Z Liang, L Ruan, C Lian, H Shi, K Chen, Z Tu
Cell Death & Disease.2015; 6(1): e1595. CrossRef
Oxaliplatin induced-neuropathy in digestive tumors
María Sereno, Gerardo Gutiérrez-Gutiérrez, César Gómez-Raposo, Miriam López-Gómez, Maria Merino-Salvador, Francisco Zambrana Tébar, Cristina Rodriguez-Antona, Enrique Casado
Critical Reviews in Oncology/Hematology.2014; 89(1): 166. CrossRef
Effect of doxorubicin, oxaliplatin, and methotrexate administration on the transcriptional activity ofBCL-2family gene members in stomach cancer cells
Dimitra Florou, Christos Patsis, Alexandros Ardavanis, Andreas Scorilas
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The kallikrein-related peptidase 13 (KLK13) gene is substantially up-regulated after exposure of gastric cancer cells to antineoplastic agents
Dimitra Florou, Konstantinos Mavridis, Andreas Scorilas
Tumor Biology.2012; 33(6): 2069. CrossRef

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A Retrospective Study of First-Line Combination Chemotherapy in Advanced Colorectal Cancer: A Korean Single-Center Experience: Soon Il Lee, Se Hoon Park, Do Hyoung Lim, Keon Woo Park, Jeeyun Lee, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Won Ki Kang; Cancer Res Treat. 2011;43(2):96-101. Published online June 30, 2011; DOI: https://doi.org/10.4143/crt.2011.43.2.96

Abstract PDF PubReader ePub

PURPOSE
Fluoropyrimidine-based combination chemotherapy, in combination with either oxaliplatin or irinotecan, has demonstrated efficacy and tolerability in treatment of advanced colorectal cancer (ACC).
MATERIALS AND METHODS
Between January 2006 and December 2007, a total of 478 ACC patients were treated with combination chemotherapy in first-line settings. Combination therapies included: 5-fluorouracil, folinic acid plus oxaliplatin (FOLFOX, n=172), 5-fluorouracil, folinic acid plus irinotecan (FOLFIRI, n=95), capecitabine plus oxaliplatin (XELOX, n=155), and capecitabine plus irinotecan (XELIRI, n=56). FOLFOX and FOLFIRI were repeated every 2 weeks, whereas XELOX and XELIRI were repeated every 3 weeks until occurrence of disease progression or unacceptable toxicity, or until a patient chose to discontinue treatment.
RESULTS
The median age was 58 years (range, 19 to 84 years) and the median chemotherapy durations for FOLFOX, FOLFIRI, XELOX, and XELIRI were 4.9, 4.5, 5.7, and 5.4 months, respectively. Combination chemotherapy regimens were generally well tolerated. The estimated median progression-free-survival (PFS) for all patients was 6.8 months (95% confidence interval, 6.3 to 7.3 months). No statistically significant difference in PFS was found among regimens used as first-line chemotherapy. Sixty percent (n=290) of patients received second or further lines of therapy after failure.
CONCLUSION
Fluoropyrimidine-based combination chemotherapy regimens appear to be equally active and tolerable as first-line therapy for ACC.

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Nineteen-year, real-world experience of first-line combination chemotherapy in patients with metastatic colorectal cancer: a propensity score analysis from southern Thailand
Jirapat Wonglhow, Chirawadee Sathitruangsak, Arunee Dechaphunkul, Patrapim Sunpaweravong
Journal of International Medical Research.2023;[Epub] CrossRef
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Si-Qi Dong, Tong-Min Wang, Jiang-Bo Zhang, Yong-Qiao He, Wen-Qiong Xue, Zi-Yi Wu, Da-Wei Yang, Lian-Jing Cao, Jing-Wen Huang, Xi-Zhao Li, Pei-Fen Zhang, Xiao-Hui Zheng, Wei-Hua Jia
Cancer Research and Treatment.2021; 53(3): 724. CrossRef

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Oxaliplatin-Induced Chronic Peripheral Neurotoxicity: A Prospective Analysis in Patients with Colorectal Cancer: Kyung Kee Baek, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Won Ki Kang, Yong Beom Cho, Seong Hyeon Yun, Hee Cheol Kim, Woo Yong Lee, Ho-Kyung Chun; Cancer Res Treat. 2010;42(4):185-190. Published online December 31, 2010; DOI: https://doi.org/10.4143/crt.2010.42.4.185

Abstract PDF PubReader ePub

Purpose

Oxaliplatin-induced chronic peripheral neurotoxicity (OXCPN) manifests as a loss of sensation and dysesthesia in the distal extremities, which may impair daily activities and increase in incidence with the amount of oxaliplatin delivered. The variation in the reported incidence and severity of OXCPN may be a consequence of differences in the baseline characteristics of patients.

Materials and Methods

This was a prospective study (ClinicalTrials.gov, NCT00977717) in which OXCPN was recorded for all consecutive colon cancer patients treated at Samsung Medical Center (Seoul, Korea) with oxaliplatin-based combination chemotherapy. The primary endpoint was the incidence of severe OXCPN (grade 2 lasting for >7 days, or grade 3). The association of severe OXCPN and pretreatment parameters was evaluated using a multivariate regression model.

Results

Between Jan 2008 and Feb 2010, 100 patients treated with adjuvant folinic acid/fluorouracil plus oxaliplatin (FOLFOX) and 266 patients treated with capecitabine plus oxaliplatin (XELOX) or FOLFOX for advanced disease were registered into our study. The median cumulative dose of oxaliplatin was 796 mg/m² (range, 85 to 1,583 mg/m²). Severe OXCPN was observed in 126 (34%) patients. Overall, 43 patients discontinued chemotherapy due to toxicity: 23 without severe OXCPN and 20 with severe OXCPN. In univariate analysis, severe OXCPN was frequently observed in patients with age ≥55 years (p<0.01), stage II or III (p<0.01), adjuvant setting (p=0.01), FOLFOX (p<0.01), performance status of 0 (p=0.02), and those with no prior chemotherapy (p<0.01). In a multivariate regression model, the number of chemotherapy cycles and the cumulative oxaliplatin dose were not associated with the development of severe OXCPN.

Conclusion

We failed to find a significant association between patient characteristics at baseline and the development of severe OXCPN after oxaliplatin-based combination chemotherapy. Pharmacogenomic profiling using genome-wide association study in these patients is underway.

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Outcomes of Modified FOLFOX-6 as First Line Treatment in Patients with Advanced Gastric Cancer in a Single Institution; Retrospective Analysis: Han Hong Lee, Hoon Hur, Soo Hong Kim, Ae Ryung Park, Wook Kim, Hae Myung Jeon; Cancer Res Treat. 2010;42(1):18-23. Published online March 31, 2010; DOI: https://doi.org/10.4143/crt.2010.42.1.18

Abstract PDF PubReader ePub

Purpose

Treatment options for patients with advanced gastric cancer remain limited. Few studies have investigated the efficacy and tolerability of the combination regimen of oxaliplatin and 5-fluorouracil with leucovorin for patients with advanced gastric cancer. The goal of this study was to examine the efficacy and toxicity of a modified FOLFOX-6 (mFOLFOX-6) regimen as a first-line chemotherapy regimen for patients with advanced gastric cancer.

Materials and Methods

From March, 2006, to December, 2007, 82 patients with advanced gastric cancer received 100 mg/m² oxaliplatin and 100 mg/m² leucovorin on the first day of treatment, followed by 2,400 mg/m² of 5-fluorouracil on the first and second days of treatment every 2 weeks as a first-line treatment.

Results

The median age of the enrolled patients was 62 years (range; 30~75). Out of 82 patients, 34 cases (41.5%) were recurrent cases after curative resection, and the other 48 cases were unresectable or non-curative resectable cases. Their response was evaluated every 6 weeks. The overall response rate was 40.2%, with 2 (2.4%) complete response and 31 (37.8%) partial responses. The median time to progression (TTP) and overall survival (OS) time were 6.0 months (95% confidence interval [CI]: 4.69~7.31) and 13.0 months (7.99~18.0), respectively. The grade 3~4 hematologic toxicities observed included neutropenia (34.1%), thrombocytopenia (7.3%), and anemia (1.2%). The gastrointestinal toxicities observed included grade 3~4 nausea (9.8%) and vomiting (7.3%). Six patients (7.3%) experienced grade 3 neuropathy. No treatment-related deaths were recorded.

Conclusion

The modified FOLFOX-6 regimen is effective and well tolerated as a first-line chemotherapy regimen for patients with advanced gastric cancer.

Citations

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Nanoparticle Polymeric Micellar Paclitaxel Versus Paclitaxel for Patients with Advanced Gastric Cancer
Fei-Yu Wang, Xiang-Ming Huang, Yu-Qing Cao, Jie Cao, Jie Ni, Ke Li, Min Lu, Xin-En Huang
Journal of Gastrointestinal Cancer.2024; 55(3): 1105. CrossRef
Prognostic significance of interim 18F‐fluorodeoxyglucose positron emission tomography–computed tomography volumetric parameters in metastatic or recurrent gastric cancer
Suk‐young Lee, Hyo Jung Seo, Sungeun Kim, Jae Seon Eo, Sang Cheul Oh
Asia-Pacific Journal of Clinical Oncology.2018;[Epub] CrossRef
Combination chemotherapy with paclitaxel and oxaliplatin as first-line treatment in patients with advanced gastric cancer
Yan-qin Lan, Ling-jun Kong, Xiao-yan Lin, Qian Xu, Xin-yan Gao, Ri-ping Wu, Xin-li Wang, Dong-ta Zhong
Cancer Chemotherapy and Pharmacology.2018; 81(6): 1007. CrossRef
Paclitaxel, oxaliplatin, 5-fluorouracil and leucovorin combination chemotherapy in patients with recurrent or metastatic gastric cancer
Yan-qin Lan, Ri-ping Wu, Xiao-bing Huang, Xin-li Wang, Dong-ta Zhong, Chuan-yong Huang, Jin-tian Song
Tumori Journal.2018; 104(1): 22. CrossRef
Comparative Analysis of the Efficacy and Safety of Oxaliplatin Plus 5-Fluorouracil/Leucovorin (Modified FOLFOX6) with Advanced Gastric Cancer Patients having a Good or Poor Performance Status
Ilhan Hacibekiroglu, Hilmi Kodaz, Bulent Erdogan, Esma Turkmen, Asim Esenkaya, Sernaz Uzunoglu, Irfan Cicin
Asian Pacific Journal of Cancer Prevention.2015; 16(6): 2355. CrossRef
Comparative analysis of the efficacy and safety of modified FOLFOX-6 and DCF regimens as first-line treatment in advanced gastric cancer
ILHAN HACIBEKIROGLU, HILMI KODAZ, BULENT ERDOGAN, ESMA TURKMEN, ASIM ESENKAYA, YILMAZ ONAL, SERNAZ UZUNOGLU, IRFAN CICIN
Molecular and Clinical Oncology.2015; 3(5): 1160. CrossRef
Clinical evaluation of cetuximab combined with an S-1 and oxaliplatin regimen for Chinese patients with advanced gastric cancer
Zhan-Dong Zhang, Ye Kong, Wei Yang, Bin Zhang, Yong-Lei Zhang, Er-Min Ma, Hong-Xing Liu, Xiao-Bin Chen, Ya-Wei Hua
World Journal of Surgical Oncology.2014;[Epub] CrossRef
Management of advanced gastric cancer
Timothy J Price, Jeremy D Shapiro, Eva Segelov, Christos S Karapetis, Nick Pavlakis, Eric Van Cutsem, Manish A Shah, Yoon-Koo Kang, Niall C Tebbutt
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Outcomes of Third-Line Docetaxel-Based Chemotherapy in Advanced Gastric Cancer Who Failed Previous Oxaliplatin-Based and Irinotecan-Based Chemotherapies
Min Jeong Lee, In Gyu Hwang, Joung-Soon Jang, Jin Hwa Choi, Byeong-Bae Park, Myung Hee Chang, Seung Tae Kim, Se Hoon Park, Myoung Hee Kang, Jung Hun Kang
Cancer Research and Treatment.2012; 44(4): 235. CrossRef
Modified FOLFOX-6 Therapy for Heavily Pretreated Advanced Gastric Cancer Refractory to Fluorouracil, Irinotecan, Cisplatin and Taxanes: A Retrospective Study
K. Tsuji, H. Yasui, Y. Onozawa, N. Boku, H. Doyama, A. Fukutomi, K. Yamazaki, N. Machida, A. Todaka, H. Taniguchi, T. Tsushima, T. Yokota
Japanese Journal of Clinical Oncology.2012; 42(8): 686. CrossRef
A rare case of acute kidney injury associated with autoimmune hemolytic anemia and thrombocytopenia after long-term usage of oxaliplatin
Isao Ito, Yasuhiko Ito, Masashi Mizuno, Yasuhiro Suzuki, Kaoru Yasuda, Takenori Ozaki, Tomoki Kosugi, Yoshinari Yasuda, Waichi Sato, Naotake Tsuboi, Shoichi Maruyama, Enyu Imai, Seiichi Matsuo
Clinical and Experimental Nephrology.2012; 16(3): 490. CrossRef
Oxaliplatin, 5-fluorouracil and leucovorin (modified FOLFOX-6) as first-line chemotherapy for advanced gastric cancer patients with poor performance status
HYEONG SU KIM, JUNG HAN KIM, HEE JUN KIM, HYUN JOO JANG, JIN BAE KIM, JI WON KIM, SO YOUNG JUNG, BYUNG CHUN KIM, DAE HYUN YANG, SOAH PARK, KEONG JU KIM, SOON IL LEE, DAE YOUNG ZANG
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Oxaliplatin, 5-FU, Folinic Acid as First-line Palliative Chemotherapy in Elderly Patients with Metastatic or Recurrent Gastric Cancer: In Sil Choi, Do-Youn Oh, Byoung-Su Kim, Keun-Wook Lee, Jee Hyun Kim, Jong-Seok Lee; Cancer Res Treat. 2007;39(3):99-103. Published online September 30, 2007; DOI: https://doi.org/10.4143/crt.2007.39.3.99

Abstract PDF PubReader ePub

Purpose

We investigated the efficacy and safety of a combination of oxaliplatin, 5-fluorouracil (5-FU), and folinic acid (FA) as first-line palliative chemotherapy for elderly patients with metastatic or recurrent gastric cancer.

Materials and Methods

The study patients were chemotherapy-naïve patients (> 65 years old) with histologically confirmed, metastatic or recurrent gastric cancer. Chemotherapy consisted of oxaliplatin 100 mg/m² and FA 100 mg/m² (2-hour infusion), and then 5-FU 2400 mg/m² (46-hour continuous infusion) every 2 weeks.

Results

A total of 37 patients were studied between April 2004 and October 2006. Of the 34 evaluable patients, none achieved a complete response (CR) and 14 achieved a partial response (PR), resulting in an overall response rate of 41.2%. The median time to progression (TTP) was 5.7 months (95% CI: 4.2~6.3 months) and the median overall survival (OS) was 9.8 months (95% CI: 4.4~12.0 months). The main hematologic toxicities were anemia and neutropenia, which were observed in 56.7% and 32.4% of the patients, respectively. Grade 3/4 neutropenia was observed in 8.1% of the patients. None of the patients experienced febrile neutropenia. Peripheral neuropathy occurred in 35.1% of the patients and all were grade 1/2.

Conclusion

This oxaliplatin/5-FU/FA regimen showed good efficacy and an acceptable toxicity profile in elderly patients with metastatic or recurrent gastric cancer.

Citations

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Case Report

Hypersensitivity Reactions to Oxaliplatin: Kyoung-Hwan Lee, Yong Jai Park, Eun Sun Kim, Hui Jeong Hwang, Byoung Yong Shim, Hoon-Kyo Kim; Cancer Res Treat. 2006;38(4):240-241. Published online December 31, 2006; DOI: https://doi.org/10.4143/crt.2006.38.4.240

Abstract PDF PubReader ePub

Oxaliplatin is a third-generation platinum compound that is used as a single agent and in combination with fluorouracil (5-FU) to treat colorectal and gastric carcinoma. The patients treated with oxaliplatin may develop hypersensitivity and idiosyncratic reactions, although these complications are known to be rare. We report here on two patients who suffered with metastatic colorectal cancer and who underwent palliative combination chemotherapy with oxaliplatin; they then developed hypersensitivity reactions to oxaliplatin. The first case had an anaphylatic reaction immediately after the beginning of the 7^th to 8^th cycle infusion of oxaliplatin. The second case developed repeated febrile episodes from the 4^th to 8^th cycles of oxaliplatin infusion. With the increasing use of oxaliplatin in clinical practice, we are now encountering an increasing incidence of suspected hypersensitivity reactions. Physicians should keep their eyes wide open and carefully observe for the clinical manifestations of these hypersensitivity reactions.

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Christina Okello
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Usman M Aliyu, Charles O Okwonna
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Rare presentation of subglottic soft-tissue swelling following FOLFOX therapy in a patient with metastatic oesophageal cancer
Siva Naga S Yarrarapu, Austin B Govero, Faeq R Kukhon, Devang K Sanghavi
BMJ Case Reports.2021; 14(4): e240938. CrossRef
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Arushi Khurana, Demytra Mitsis, Gurukripa N Kowlgi, Lisa M Holle, Jessica M Clement
Journal of Oncology Pharmacy Practice.2016; 22(2): 319. CrossRef
Hypersensitivity Reactions to Oxaliplatin: Clinical Features and Risk Factors in Koreans
Mi-Yeong Kim, Sung-Yoon Kang, Suh-Young Lee, Min-Suk Yang, Min-Hye Kim, Woo-Jung Song, Sae-Hoon Kim, Yo-Jung Kim, Keun-Wook Lee, Sang-Heon Cho, Kyung-Up Min, Jong-Seok Lee, Jee-Hyun Kim, Yoon-Seok Chang
Asian Pacific Journal of Cancer Prevention.2012; 13(4): 1209. CrossRef
Revisión de las reacciones de hipersensibilidad a antineoplásicos
S. Cortijo-Cascajares, M.J. Jiménez-Cerezo, A. Herreros de Tejada
Farmacia Hospitalaria.2012; 36(3): 148. CrossRef

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Original Article

Phase II Study of Oxaliplatin, 5-fluorouracil, and Leucovorin in Relapsed or Metastatic Colorectal Cancer as Second Line Therapy: Duk-Joo Lee, Ho-Suk Oh, Jung-Hye Choi, Young-Yeul Lee, In-Soon Kim, Myung-Ju Ahn; Cancer Res Treat. 2006;38(4):201-205. Published online December 31, 2006; DOI: https://doi.org/10.4143/crt.2006.38.4.201

Abstract PDF PubReader ePub: Purpose
The purpose of the study was to assess the efficacy and safety of biweekly oxaliplatin in combination with leucovorin (LV)-modulated bolus plus infusion of 5-fluorouracil (5-FU) in patients with relapsed or metastatic colorectal cancer (CRC) as a second line therapy.
Materials and Methods
Between November 2002 and October 2005, 26 patients with histologically confirmed relapsed or metastatic CRC were enrolled. All patients were previously treated with irinotecan-based combination chemotherapy. The chemotherapy regimen consisted of oxaliplatin 85 mg/m² on day 1; LV 200 mg/m² on days 1 and 2; and 5-FU 400 mg/m² bolus IV with 600 mg/m² with a 22-hour infusion on days 1 and 2 every 2 weeks.
Results
The median age of the 26 patients was 50.5 years (range, 31~72). Their metastatic sites included: the liver (42.3%), peritoneum (26.9%), lung (23.1%) and ovary (7.7%). Twenty five patients were evaluated for their response. Four patients achieved partial responses and 15 patients had stable disease. The overall response rate was 16% (95% confidence interval; 1.7~30.3%). The median follow-up duration for the surviving patients was 7.4 months (range, 2.08~21.2). Median overall survival (OS) and 1-year OS rates were 16.7 months and 63.9%, respectively. The most common hematological toxicities were: NCI grade I/II leucopenia (49.3%), grade I/II neutropenia (41%) and grade I/II anemia (65.2%). The main non-hematological toxicities were: grade I/II peripheral neuropathy (16.1% and 21.5%, respectively) and nausea/vomiting (23.6%/18.5%). There was no life-threatening toxicity.
Conclusion
The oxaliplatin, 5-FU and LV combination chemotherapy, scheduled as a biweekly protocol, was effective and well tolerated in the treatment of relapsed or metastatic colorectal cancer patients as second line chemotherapy.

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Review Article

Lapatinib - Overview and Current Role in Metastatic Breast Cancer: Arlene Chan; Cancer Res Treat. 2006;38(4):198-200. Published online December 31, 2006; DOI: https://doi.org/10.4143/crt.2006.38.4.198

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Original Articles

Combination Chemotherapy of Oxaliplatin, 5-Fluorouracil and Low Dose Leucovorin in Patients with Advanced Colorectal Cancer: Yoon Mi Shin, Hae Suk Han, Seong Woo Lim, Byung Chul Kim, Kyung Suck Cheoi, Young Ook Eum, Seung Taek Kim, Ki Hyeong Lee; Cancer Res Treat. 2005;37(5):284-289. Published online October 31, 2005; DOI: https://doi.org/10.4143/crt.2005.37.5.284

Abstract PDF PubReader ePub

Purpose

The aim of this study was to evaluate the efficacy and tolerability of the oxaliplatin, 5-fluorouracil (5-FU) and low dose leucovorin (LV) combination in patients with advanced colorectal cancer.

Materials and Methods

Patients with unresectable or recurrent colorectal carcinomas were prospectively accrued. Up to one prior chemotherapy regimen was allowed. Patients received oxaliplatin, 85 mg/m², administered as a 2-hour infusion on day 1, followed by LV, 20 mg/m², as a bolus and 5-FU, 1,500 mg/m², via continuous infusion for 24 hours on days 1 and 2. Treatment was repeated every 2 weeks until disease progression or adverse effects prohibited further therapy.

Results

Between August 1999 and May 2004, 31 patients were enrolled in this study. Of the patients enrolled, 24 and 31 were evaluable for tumor response and survival analysis, respectively. The patients' characteristics included a median age of 59, with 6 (19%) having had prior chemotherapy. No patient achieved a complete response, but nine (38%) attained a partial response. Seven (29%) patients maintained a stable disease and 8 (33%) experienced increasing disease. The median duration of the response was 6 months. After a median follow-up of 9.6 months, the median time to progression was 3.8 months, with a median survival of 10.7 months. The hematological toxicities were mild to moderate, with no treatment-related mortality or infection. The major non-hematological toxicity was gastrointestinal toxicity.

Conclusion

The combination chemotherapy of oxaliplatin, low dose LV and continuous infusion of 5-FU is safe and has a cost-benefit, but is a moderately effective regimen in advanced colorectal cancer. A randomized trial comparing low and high dosages of leucovorin in the FOLFOX regimen is warranted.

Citations

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Extracellular vesicles derived from Lactobacillus plantarum restore chemosensitivity through the PDK2-mediated glucose metabolic pathway in 5-FU-resistant colorectal cancer cells
JaeJin An, Eun-Mi Ha
Journal of Microbiology.2022; 60(7): 735. CrossRef
Prognostic and Predictive Role of Excision Repair Cross-complementation Group 1 and Thymidylate Synthase in Colorectal Carcinoma Patients Received FOLFOX Chemotherapy: An Immunohistochemical Study
Dalia M. Badary, Mai M. Elkabsh, Hussam H. Mady, Adel Gabr, Sana S. Kroosh
Applied Immunohistochemistry & Molecular Morphology.2020; 28(10): 741. CrossRef
Outpatient-basis Chemotherapy of Oxaliplatin, 5-fluorouracil, and Leucovorin as First-line Treatment for Patients with Metastatic or Recurrent Colorectal Cancer
Joon Ho Moon, Jong Gwang Kim, Sang Kyun Sohn, Jin Ho Baek, Yoon Young Cho, Yee Soo Chae, Byung Min Ahn, Shi Nae Kim, Soo Jung Lee, In Taek Lee, Gyu Seog Choi, Soo Han Jun
Journal of Korean Medical Science.2007; 22(3): 400. CrossRef

8,764 View
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Oxaliplatin with Biweekly Low Dose Leucovorin and Bolus and Continuous Infusion of 5-fluorouracil (Modified FOLFOX 4) as a Salvage Therapy for Patients with Advanced Gastric Cancer: Sung-Hwan Suh, Hyuk-Chan Kwon, Ji-Hoon Jo, Young-Rak Cho, Bong-Gun Seo, Dong-Mee Lee, Sung-Hyun Kim, Jae-Seok Kim, Hyo-Jin Kim; Cancer Res Treat. 2005;37(5):279-283. Published online October 31, 2005; DOI: https://doi.org/10.4143/crt.2005.37.5.279

Abstract PDF PubReader ePub

Purpose

To determine the activity and the toxicity associated with a low dose regimen of leucovorin (LV) plus 5-fluorouracil (5-FU) combined with oxaliplatin every two weeks (modified FOLFOX 4) as a salvage therapy for advanced gastric cancer patients.

Materials and Methods

Between December 2003 and December 2004, 33 patients were enrolled in this study. The patients were treated with oxaliplatin 85 mg/m² as a 2-hour infusion on the first day plus LV 20 mg/m² over 10 minutes. Subsequently, the patients were given a 5-FU bolus 400 mg/m² followed by a 22-hour continuous infusion of 600 mg/m² on days 1~2. The treatment was repeated at 2 week intervals.

Results

The median age of the patients was 50 years (range: 31~74), 82% (27/33) had the Eastern Cooperative Oncology Group performance status was 0 and 1. Of the 30 patients who could be evaluated for their tumor response, 8 achieved a partial response, with an overall response rate of 26.7% (95% confidence interval (CI): 20.5~32.7%). Fifteen patients (50%) showed stable disease and 7 patients (23.3%) progressed during the course of treatment. The median time from the start of chemotherapy to progression was 3.5 months (95% CI: 2.6~4.4 months) and the median overall survival time was 7.9 months (95% CI: 5.9~9.9 months). The major grade 3/4 hematological toxicity encountered included neutropenia (45.4%) and thrombocytopenia (3.0%). Neutropenic fever occurred during only 2 of the 178 cycles. The most common non-hematological toxicity encountered was grade 1/2 nausea/vomiting, which occurred in 18.2% of patients, diarrhea in 12.1% and neuropathy in 15.2%. There were no treatment related deaths.

Conclusion

The modified FOLFOX 4 regimen appears to be a safe and effective salvage therapy for advanced gastric cancer patients.

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PrPC Aptamer Conjugated–Gold Nanoparticles for Targeted Delivery of Doxorubicin to Colorectal Cancer Cells
Gyeongyun Go, Chang-Seuk Lee, Yeo Min Yoon, Ji Ho Lim, Tae Hyun Kim, Sang Hun Lee
International Journal of Molecular Sciences.2021; 22(4): 1976. CrossRef
A Phase I Study of Pevonedistat Plus Capecitabine Plus Oxaliplatin in Patients With Advanced Gastric Cancer Refractory to Platinum (NCCH-1811)
Hirokazu Shoji, Daisuke Takahari, Hiroki Hara, Kengo Nagashima, Jun Adachi, Narikazu Boku
Future Science OA.2021;[Epub] CrossRef
Salvage chemotherapy with the combination of oxaliplatin, leucovorin, and 5-fluorouracil in advanced gastric cancer refractory or intolerant to fluoropyrimidines, platinum, taxanes, and irinotecan
Chihiro Kondoh, Shigenori Kadowaki, Azusa Komori, Yukiya Narita, Hiroya Taniguchi, Takashi Ura, Masashi Ando, Kei Muro
Gastric Cancer.2018; 21(6): 1050. CrossRef
Pemetrexed for previously treated patients with metastatic gastric cancer: a prospective phase II study
D S Zhang, Y Jin, H Y Luo, Z Q Wang, M Z Qiu, F H Wang, Y H Li, R H Xu
British Journal of Cancer.2015; 112(2): 266. CrossRef
Third-line docetaxel chemotherapy for recurrent and metastatic gastric cancer
Ji Hyun Lee, Sung-Hyun Kim, Sung Yong Oh, Suee Lee, Hojin Lee, Hye Jung Lee, Hyo-Jin Kim
The Korean Journal of Internal Medicine.2013; 28(3): 314. CrossRef
A Retrospective Study of the Safety and Efficacy of a First-Line Treatment with Modified FOLFOX-4 in Unresectable Advanced or Recurrent Gastric Cancer Patients
Yung-Sung Yeh, Hsiang-Lin Tsai, Cheng-Jen Ma, Deng-Chyang Wu, Chien-Yu Lu, I-Chen Wu, Ming-Feng Hou, Jaw-Yuan Wang
Chemotherapy.2012; 58(5): 411. CrossRef
Modified FOLFOX-6 Therapy for Heavily Pretreated Advanced Gastric Cancer Refractory to Fluorouracil, Irinotecan, Cisplatin and Taxanes: A Retrospective Study
K. Tsuji, H. Yasui, Y. Onozawa, N. Boku, H. Doyama, A. Fukutomi, K. Yamazaki, N. Machida, A. Todaka, H. Taniguchi, T. Tsushima, T. Yokota
Japanese Journal of Clinical Oncology.2012; 42(8): 686. CrossRef
PEG‐liposomal oxaliplatin induces apoptosis in human colorectal cancer cells via Fas/FasL and caspase‐8
Chuang Yang, Hai‐Zhong Liu, Zhong‐Xue Fu
Cell Biology International.2012; 36(3): 289. CrossRef
Multicenter phase II study of docetaxel plus oxaliplatin combination chemotherapy in patients with advanced gastric cancer: Daegu Gyeongbuk Oncology Group
J G Kim, S K Sohn, Y S Chae, H S Song, K-Y Kwon, Y R Do, M K Kim, K H Lee, M S Hyun, H M Ryoo, S H Bae, K U Park, W S Lee, J H Baek, H Y Chung, W Yu
British Journal of Cancer.2008; 98(3): 542. CrossRef
A Phase II Study of Paclitaxel and Cisplatin as Salvage Therapy for Patients with Advanced or Metastatic Gastric Cancer
Bong-Gun Seo, Sung Yong Oh, Dong Mee Lee, Hyun Seung Yoo, Suee Lee, Seong-Geun Kim, Sung-Hyun Kim, Hyuk-Chan Kwon, Hyo-Jin Kim
Cancer Research and Treatment.2007; 39(1): 6. CrossRef
Prognostic value of expression of ERCC1, thymidylate synthase, and glutathione S-transferase P1 for 5-fluorouracil/oxaliplatin chemotherapy in advanced gastric cancer
H.-C. Kwon, M.S. Roh, S.Y. Oh, S.-H. Kim, M.C. Kim, J.-S. Kim, H.-J. Kim
Annals of Oncology.2007; 18(3): 504. CrossRef

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Oxaliplatin/5-FU without Leucovorin Chemotherapy in Metastatic Colorectal Cancer: Byoung Yong Shim, Kang Moon Lee, Hyeon-Min Cho, Hyun Jin Kim, Hong Joo Cho, Jinmo Yang, Jun-Gi Kim, Hoon-Kyo Kim; Cancer Res Treat. 2005;37(4):212-215. Published online August 31, 2005; DOI: https://doi.org/10.4143/crt.2005.37.4.212

Abstract PDF PubReader ePub

Purpose

Fluorouracil (5-FU) and leucovorin combination therapy have shown synergistic or additive effect against advanced colorectal cancer, but the frequency of mucositis and diarrhea is increased. Most previous studies have used high dose leucovorin (300~500 mg/m²). However, some studies of oxaliplatin and 5-FU with low-dose or high-dose leucovorin in Korea have shown similar response rates. Therefore, we studied the necessity of leucovorin and evaluated the objective tumor response rates and toxicities of a regimen of oxaliplatin and 5-FU without leucovorin every 2 weeks in metastatic colorectal cancer patients.

Materials and Methods

Twenty-four patients with metastatic colorectal cancer were enrolled between January 2002 and March 2003. Patients received 85 mg/m² of oxaliplatin on day 1, a bolus 5-FU 400 mg/m² on day 1 and a continuous 5-FU infusion at 600 mg/m²/ 22 hours days 1 and 2, every 2 weeks.

Results

Of the 24 patients treated, 17 patients received previous 5FU with leucovorin and/or other chemotherapy. Three patients could not be evaluated. Five partial responses were observed with overall response rate of 21% (n=24). Of the previous chemotherapy group (n=17), 4 partial responses were observed with response rate of 24%. Median overall survival was 18 months (range 4~32 months) and median progression free survival was 4 months (range 2~6 months). This regimen was well tolerated and only 1 grade 3 anemia was observed.

Conclusion

Oxaliplatin/5-FU combination therapy without leucovorin achieved a relatively high response rate even in patients resistant to the previous 5-FU chemotherapy, and toxicity was minimal.

Citations

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Clinicopathological Features and Oncological Outcomes of Early and Late Recurrence in Stage III Colorectal Cancer Patients after Adjuvant Oxaliplatin-Based Therapy
Yu-Tang Chang, Hsiang-Lin Tsai, Yen-Cheng Chen, Ching-Chun Li, Ching-Wen Huang, Po-Jung Chen, Wei-Chih Su, Tsung-Kun Chang, Yung-Sung Yeh, Tzu-Chieh Yin, Jaw-Yuan Wang, Weiren Luo
Journal of Oncology.2023; 2023: 1. CrossRef
Targeting the SPHK1/HIF1 Pathway to Inhibit Colorectal Cancer Stem Cells Niche
Saeideh Gholamzadeh Khoei, Hamid Sadeghi, Fateme Karimi Dermani
Journal of Gastrointestinal Cancer.2020; 51(2): 716. CrossRef
Efficacy of 5-FU or Oxaliplatin Monotherapy over Combination Therapy in Colorectal Cancer
Maria Toloudi, Panagiotis Apostolou, Ioannis Papasotiriou
Journal of Cancer Therapy.2015; 06(04): 345. CrossRef
Gene Expression Changes in Colorectal Cancer during Metronomic Chemotherapy and High-Concentration Drug Administration
Panagiotis Apostolou, Maria Toloudi, Irene Kalliara, Vasiliki Kipourou, Ioanna Tourna, Ioannis Papasotiriou
Journal of Cancer Therapy.2015; 06(08): 679. CrossRef

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4 Crossref

The Efficacy of a Modified Chronomodulated Infusion of Oxaliplatin, 5-Fluorouracil and Leucovorin in Advanced Colorectal Cancer (Preliminary Data): Ji Young Park, Si-Young Kim, Jae Jin Lee, Hwi Joong Yoon, Kyung Sam Cho; Cancer Res Treat. 2004;36(3):199-204. Published online June 30, 2004; DOI: https://doi.org/10.4143/crt.2004.36.3.199

Abstract PDF PubReader ePub

Purpose

To determine the efficacy and tolerability of a modified chronomodulated infusion of oxaliplatin, 5-fluorouracil (5-FU) and leucovorin in the treatment of advanced colorectal cancer.

Materials and Methods

Sixteen patients with relapsed or metastatic colorectal cancer were treated with an intravenous infusion of oxaliplatin 25 mg/m², 5-FU 700 mg/m² and leucovorin 20 mg/m² on days 1 to 5. The infusion of oxaliplatin was chronomodulated with a peak delivery rate at 16:00 p.m., with 5-FU infused constantly overnight. Each course was repeated every 21 days.

Results

The response rate was 38.5% (95% confidence interval [CI], 13.9% to 68.4%) in the 13 measurable patients, including 1 complete response (7.7%) and 4 partial responses (30.8%). Five patients (38.5%) had a stable disease and 3 (23.0%) a progressive disease. Three patients without a measurable lesion had improved status. The median time to progression and overall survival were 29 weeks and 85 weeks, respectively. Grade 3 thrombocytopenia occurred in 2.5% (2 cycles) and grade 3 vomiting in 12.5% (2 patients). Anorexia, stomatitis, diarrhea, pruritus, alopecia and peripheral neuropathy were mild and tolerable.

Conclusion

The modified chronomodulated infusion of oxaliplatin, 5-FU and leucovorin is effective and tolerable, but the number of patients was too small. Further study will be needed to confirm the efficacy of this regimen with a larger population of patients.

Citations

Citations to this article as recorded by

Combination Chemotherapy of Oxaliplatin, 5-Fluorouracil and Low Dose Leucovorin in Patients with Advanced Colorectal Cancer
Yoon Mi Shin, Hae Suk Han, Seong Woo Lim, Byung Chul Kim, Kyung Suck Cheoi, Young Ook Eum, Seung Taek Kim, Ki Hyeong Lee
Cancer Research and Treatment.2005; 37(5): 284. CrossRef

9,262 View
45 Download
1 Crossref

Oxaliplatin with Biweekly, Low Dose Leucovorin and Bolus and Continuous Infusion 5-fluorouracil (Modified FOLFOX 4) as First-line Therapy for Patients with Metastatic Colorectal Cancer: Hyuk-Chan Kwon, Kyoung Tae Kim, Shin Ae Lee, Jong-Sung Park, Sung-Hyun Kim, Jae-Seok Kim, Hyo Jin Kim; Cancer Res Treat. 2004;36(2):115-120. Published online April 30, 2004; DOI: https://doi.org/10.4143/crt.2004.36.2.115

Abstract PDF PubReader ePub

Purpose

To determine the activity and toxicities of low dose leucovorin (LV) plus fluorouracil (5-FU) regimen, combined with oxaliplatin every two weeks (modified FOLFOX 4), as a first-line therapy for patients with metastatic colorectal cancer.

Materials and Methods

Between March 2001 and August 2003, fifty-five patients were enrolled in this study. Patients were treated with oxaliplatin 85 mg/m² as a 2-hour infusion at days 1 plus LV 20 mg/m² over 10 minutes, followed by 5-FU bolusa 400 mg/m² bolus and 22 hour continuous infusion of 600 mg/m² 5-FU at day 1~2. This treatment was repeated in 2 week intervals.

Results

The objective response rate was 40% on an intent-to-treatment analysis. Three patients (6%) demonstrated a complete response and nineteen patients (38%) showeda partial response. Sixteen patients (32%) showed a stable disease and eleven patients (22%) progressed during the course of the treatment. The median time to progression and overall survival time wereas 6.6 months (95% CI: 4.98~8.02 months) and the median overall survival time was 17.0 months (95% CI: 9.15~24.85 months) from the start of the chemotherapy, respectively. A total of 275 cycles were analyzed for toxicity. Major hematologic toxicities included grade 1~2 anemia (23.5%), neutropenia (25.3%) and thrombocytopenia (10.6%). There were only 2 cycles of neutropenic fever. The most common non-hematologic toxicities were grade 1~2 nausea/vomiting (10.9%), diarrhea (9.1%) and grade 1 neuropathy (18.0%). There was no treatment related death.

Conclusion

The modified folfox 4 regimen is safe and effective regimen as a first-line therapy in advanced colorectal cancer patients.

Citations

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A Phase II Study of Modified FOLFOX4 for Colorectal Cancer Patients with Peritoneal Carcinomatosis
Dong Hyun Lee, Sung Yong Oh, Yu Rim Lee, Seok Jae Huh, Hyun Hwa Yoon, Sung Hyun Kim, Suee Lee, Ji Hyun Lee, Young Kim, Hyo-Jin Kim, Hyuk-Chan Kwon
Cancer Research and Treatment.2011; 43(4): 225. CrossRef
Outpatient-basis Chemotherapy of Oxaliplatin, 5-fluorouracil, and Leucovorin as First-line Treatment for Patients with Metastatic or Recurrent Colorectal Cancer
Joon Ho Moon, Jong Gwang Kim, Sang Kyun Sohn, Jin Ho Baek, Yoon Young Cho, Yee Soo Chae, Byung Min Ahn, Shi Nae Kim, Soo Jung Lee, In Taek Lee, Gyu Seog Choi, Soo Han Jun
Journal of Korean Medical Science.2007; 22(3): 400. CrossRef
Oxaliplatin/5-FU without Leucovorin Chemotherapy in Metastatic Colorectal Cancer
Byoung Yong Shim, Kang Moon Lee, Hyeon-Min Cho, Hyun Jin Kim, Hong Joo Cho, Jinmo Yang, Jun-Gi Kim, Hoon-Kyo Kim
Cancer Research and Treatment.2005; 37(4): 212. CrossRef
Combination Chemotherapy of Oxaliplatin, 5-Fluorouracil and Low Dose Leucovorin in Patients with Advanced Colorectal Cancer
Yoon Mi Shin, Hae Suk Han, Seong Woo Lim, Byung Chul Kim, Kyung Suck Cheoi, Young Ook Eum, Seung Taek Kim, Ki Hyeong Lee
Cancer Research and Treatment.2005; 37(5): 284. CrossRef
Oxaliplatin with Biweekly Low Dose Leucovorin and Bolus and Continuous Infusion of 5-fluorouracil (Modified FOLFOX 4) as a Salvage Therapy for Patients w ith Advanced G astric Cancer
Sung-Hwan Suh, Hyuk-Chan Kwon, Ji-Hoon Jo, Young-Rak Cho, Bong-Gun Seo, Dong-Mee Lee, Sung-Hyun Kim, Jae-Seok Kim, Hyo-Jin Kim
Cancer Research and Treatment.2005; 37(5): 279. CrossRef
Oxaliplatin: Is It a New Standard Weapon for Colorectal Cancer?
Si-Young Kim
Cancer Research and Treatment.2004; 36(2): 91. CrossRef

10,288 View
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6 Crossref

Combination Chemotherapy of Oxaliplatin and Capecitabine in Patients with Metastatic Colorectal Cancer: a Pilot Study: Myung Ju Ahn, Ho Suck Oh, Jung Hye Choi, Young Yeul Lee, In Soon Kim, Il Young Choi, Oh Young Lee, Heung Woo Lee; Cancer Res Treat. 2003;35(5):407-410. Published online October 31, 2003; DOI: https://doi.org/10.4143/crt.2003.35.5.407

Abstract PDF

PURPOSE
To evaluate the efficacy and toxicity of oxaliplatin and capecitabine in patients with metastatic colorectal cancer. MATERIALS AND METHODS: Between December 2001 and April 2003, fourteen patients were enrolled in this study. Oxaliplatin, 80 mg/m(2), was administered intravenously on day 1, and capecitabine, 1, 250 mg/m(2) bid po (total daily dose 2, 500 mg/m(2)), was given on days 1~14 of 3 week cycles. RESULTS: The median age of the patients was 57 years (range: 41~74), and the most common sites of metastasis were liver, lung or lymph node. Of the 12 evaluable patients, the overall response rate was 41.7%, but with no complete response. The median response duration and median progression free survival of 12 patients were 42 and 24.4 weeks, respectively. The median overall survival was not reached. A median 6 (range: 1~9), and a total 80, cycles were administered to 14 patients. 80 cycles were evaluable for toxicity. The most common hematological toxicities were NCI grades I/II anemia (45%), leucopenia (33.75%) and thrombocytopenia (17.5%). The most common non-hematological toxicities were nausea/ vomiting (28.75/5%) and neurotoxicity (8.75%). Hand and foot syndrome was noted in only 3.75%. There was no life-threatening toxicity.
CONCLUSION
Oxaliplatin and oral capecitabine combination chemotherapy showed significant activity and favorable toxicity in patients with metastatic colorectal cancer. Further studies, with larger numbers of patients and long-tern follow-up will be needed.

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Case Report: Vision Loss Induced by Capecitabine in Patient with Preexisting Left Eyes Blind
Paul Matte, Michel Ducreux
Case Reports in Oncology.2023; : 480. CrossRef
Phase II study of capecitabine and irinotecan combination chemotherapy in patients with advanced gastric cancer
J H Baek, J G Kim, S B Jeon, Y S Chae, D H Kim, S K Sohn, K B Lee, Y J Choi, H J Shin, J S Chung, G J Cho, H Y Jung, W Yu
British Journal of Cancer.2006; 94(10): 1407. CrossRef

4,713 View
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2 Crossref

Antitumor Activity of Oxaliplatin, 5-FU and Paclitaxel Given Alone or in Combination with ZD1839 in Human Gastric Carcinoma Cells in vitro: Ji Hyun Jang, Sang Hak Lee, Jin Hyoung Kang, Hee Sik Sun, Kazuto Nishio, Nagahiro Saijo, Hyo Jeong Kuh; Cancer Res Treat. 2002;34(5):372-381. Published online October 31, 2002; DOI: https://doi.org/10.4143/crt.2002.34.5.372

Abstract PDF

PURPOSE
Oxaliplatin (LOHP), 5-FU, and paclitaxel (PTX) are considered highly active against advanced gastric carcinomas, and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, ZD1839 is considered as a good candidate for the treatment of gastric cancers when given alone or in combination with cytotoxic agents. The present study evaluated the antitumor effects of these agents in SNU-1 human gastric cancer cells either alone or when given as a doublet (i.e., as a cytotoxic-cytostatic combination).
MATERIALS AND METHODS
We selected SNU-1 cells that showed DNA mismatch repair (MMR) deficiency and EGFR overexpression. Growth inhibition was measured by MTT and by direct cell counting and cell cycle distribution by flow cytometry. The combination index (CI) was used to describe synergistic interaction.
RESULTS
The four drugs showed IC50s ranging from 1.81 nM to 13.2microM. MTT assay appeared to underestimate the cytotoxicity of PTX, which was attributed to a significant resistant fraction (32%). LOHP and PTX induced G2/M arrest, 5-FU increased in S phase, and ZD1839 in-creased in G1 in a concentration dependent manner. PTX ZD1839 showed the greatest synergism and LOHP ZD1839 showed a similar result. The cell cycle effect of PTX was potentiated by the coadministration of ZD1839. A previously developed cytostatic TPi model was used to assess the contribution of cell cycle arrest to overall growth inhibition, and 64% and 80% of the overall growth inhibition was attributed to cell cycle arrest for LOHP and PTX, when exposed to 7.55microM and 10 nM for 72 hr, respectively.
CONCLUSION
This study demonstrates the antitumor activity and significant cell cycle arrest effect of ZD1839 against human gastric carcinoma cells and its synergistic interaction with LOHP and PTX. These results provide a preclinical rationale for the clinical development of ZD1839 and its use in combination with LOHP or PTX against human gastric cancers that express EGFR.

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Connecting Agent-Based Models with High-Dimensional Parameter Spaces to Multidimensional Data Using SMoRe ParS: A Surrogate Modeling Approach
Daniel R. Bergman, Kerri-Ann Norton, Harsh Vardhan Jain, Trachette Jackson
Bulletin of Mathematical Biology.2024;[Epub] CrossRef
A confidence building exercise in data and identifiability: Modeling cancer chemotherapy as a case study
Marisa C. Eisenberg, Harsh V. Jain
Journal of Theoretical Biology.2017; 431: 63. CrossRef

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2 Crossref

A Phase II Study of Oxaliplatin Combined with 5-Fluorouracil and Leucovorin (Mayo Clinic Regimen) in 5-Fluorouracil Refractory Colorectal Cancer: Yee Zee Bae, Jae Hyuk Jung, Chang Hoon Moon, Seong Hyun Kim, Hyuk Chan Kwon, Jae Seok Kim, Hyo Jin Kim; Cancer Res Treat. 2002;34(3):218-222. Published online June 30, 2002; DOI: https://doi.org/10.4143/crt.2002.34.3.218

Abstract PDF

PURPOSE
There are few therapeutic options in patients with colorectal cancer that have progressed or recurred following 5-fluorouracil (5-FU) based therapy. We evaluated the efficacy and toxicity of oxaliplatin, 5-FU, leucovorin (Mayo clinic regimen) in 5-FU pretreated advanced colorectal cancer patients. MATERIALS AND METGODS: Twenty-eight patients were enrolled in this study between January 1999 and May 2001. Patients were treated with oxaliplatin 150 mg/m2 on day 1 as a 2-hr infusion and 5-FU 425 mg/m2, leucovorin 20 mg/m2, bolus for 5 days. Treatment courses were repeated in 4-week intervals.
RESULTS
The objective response rate was 25% for 28 assessable patients, all cases registered a partial response. Eleven patients (39%) demonstrated stable disease, and ten (36%) progressed. The median response duration was 5.5 months, and the median time to progression was 6.3 months. The median overall survival time was 13.5 months from the start of the chemotherapy. From the 120 cycles analyzed, grade 3,4 hematologic toxicities included neutropenia: 1.6%, and thrombocytopenia: 1.6%. The frequent grade 3.4 non-hematologic adverse reactions were nausea/vomiting (25.0%), diarrhea (14.3%), stomititis (3.6%), and neuropathy (3.6%). There were no treatment-related deaths.
CONCLUSION
This phase II study had relatively higher toxicity than previous studies, and did not show an increased significant response rate. These high levels of toxicity suggest that the study treatment combination of oxaliplatin with a full dose Mayo clinic regimen arm is no feasible. Therefore, this regimen will be discontinued and a safer regimen will be adopted.

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Effect of Betulinic Acid on Anticancer Drug‐Resistant Colon Cancer Cells
Gwon‐Ryul Jung, Kyung‐Jong Kim, Cheol‐Hee Choi, Tae‐Beum Lee, Song Iy Han, Hyo‐Kyung Han, Sung‐Chul Lim
Basic & Clinical Pharmacology & Toxicology.2007; 101(4): 277. CrossRef
Oxaliplatin/5-FU without Leucovorin Chemotherapy in Metastatic Colorectal Cancer
Byoung Yong Shim, Kang Moon Lee, Hyeon-Min Cho, Hyun Jin Kim, Hong Joo Cho, Jinmo Yang, Jun-Gi Kim, Hoon-Kyo Kim
Cancer Research and Treatment.2005; 37(4): 212. CrossRef
The Efficacy of a Modified Chronomodulated Infusion of Oxaliplatin, 5-Fluorouracil and Leucovorin in Advanced Colorectal Cancer (Preliminary Data)
Ji Young Park, Si-Young Kim, Jae Jin Lee, Hwi Joong Yoon, Kyung Sam Cho
Cancer Research and Treatment.2004; 36(3): 199. CrossRef
Oxaliplatin with Biweekly, Low Dose Leucovorin and Bolus and Continuous Infusion 5-fluorouracil (Modified FOLFOX 4) as First-line Therapy for Patients with Metastatic Colorectal Cancer
Hyuk-Chan Kwon, Kyoung Tae Kim, Shin Ae Lee, Jong-Sung Park, Sung-Hyun Kim, Jae-Seok Kim, Hyo Jin Kim
Cancer Research and Treatment.2004; 36(2): 115. CrossRef

4,187 View
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Combination Chemotherapy of Oxaliplatin, 5-Fluorouracil, and Leucovorin in 5-Fluorouracil-Pretreated Patients with Metastatic Colorectal Cancer: Soo Mee Bang, Eun Kyung Cho, Jae Hwan Oh, Heung Moon Chang, Jin Seok Ahn, Jung Ae Lee, Young Iee Park, Myung Jue Ahn, Young Suk Park, Dong Bok Shin, Jae Hoon Lee; Cancer Res Treat. 2001;33(5):414-419. Published online October 31, 2001; DOI: https://doi.org/10.4143/crt.2001.33.5.414

Abstract PDF

PURPOSE
To evaluate the efficacy and toxicity of oxaliplatin in combination with 5-fluorouracil (5-FU) and leucovorin (LV) in patients with metastatic colorectal cancer who previously treated with 5-FU-based chemotherapy.
MATERIALS AND METHODS
Between April 1999 and January 2001, thirty-two patients were enrolled in this study. Oxaliplatin 130 mg/m2 was given intravenously (IV) on day 1 as was 5-FU 500 mg/m2 IV followed by continuous infusion of 5-FU 3,000 mg/m2 and LV 100 mg/m2 for 48 hours administered every 3 weeks. Six patients had received 5-FU as an adjuvant setting and 26 patients as a palliative regimen.
RESULTS
The median age of the patients was 50 years (range; 19-69) and the dominant sites of metastasis were the liver, lung or both in 9, 5 and 2 patients respectively. In 30 evaluable patients, the overall response rate was 27% including 1 complete response and 7 partial responses. The median response duration was 28 weeks (95% confidence interval; 22~34 weeks) and the median progression free survival of all patients was 24 weeks (95% confidence interval; 15~33 weeks). A median 5 cycles (range; 2~9) and total 155 cycles were performed in 32 patients. 150 cycles were evaluable for toxicity. The most common hematologic toxicity was grade 1~2 anemia in 78 cycles (52%). Leukopenia (39%) and thrombocytopenia (23%) were fully reversible. The most common non-hematologic toxicity was nausea/vomiting (43/30%) followed by diarrhea (23%), hepatotoxicity (21%) and neurotoxicity (21%). One patient ceased therapy due to grade 4 diarrhea. No other severe toxicity interrupted this treatment.
CONCLUSION
Oxaliplatin, 5-FU and LV in combination showed significant activity in previously treated metastatic colorectal cancer with favorable toxicity.

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Oxaliplatin/5-FU without Leucovorin Chemotherapy in Metastatic Colorectal Cancer
Byoung Yong Shim, Kang Moon Lee, Hyeon-Min Cho, Hyun Jin Kim, Hong Joo Cho, Jinmo Yang, Jun-Gi Kim, Hoon-Kyo Kim
Cancer Research and Treatment.2005; 37(4): 212. CrossRef

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A Phase II Study of Oxaliplatin, 5-Fluorouracil, and Leucovorin in 5- Fluorouracil-Pretreated Metastatic Colorectal Cancer: Keun Seok Lee, Won Sup Lee, Hark Kyun Kim, Joo Young Jeong, Dae Seog Heo, Yung Jue Bang, Noe Kyeong Kim; J Korean Cancer Assoc. 2001;33(2):99-105.

Abstract PDF: PURPOSE
To evaluate antitumor response, time to progression, and toxicities of oxaliplatin, 5- fluorouracil (5-FU), and leucovorin (LV) continuous infusion in patients with metastatic colorectal cancer who progressed during or after treatment with a 5-FU-containing regimen.
MATERIALS AND METHODS
Forty-eight patients with metastatic colorectal cancer, who progressed while receiving or after discontinuing palliative chemotherapy with 5- FU-based regimen, were enrolled in this study. Treatment consisted of oxaliplatin (85 mg/m2 on day 1) as a 2-hour infusion followed by bolus 5-FU (400 mg/m2 on day 1), and 5-FU 48-hour infusion 2.4~3 g/m2 concurrently with LV 48-hour infusion 150 mg/m2, without mixing. Cycles were repeated at 2-week intervals. The dose of 5-FU was modified, depending on the hematologic toxicity profile.
RESULTS
The objective response rate was 28% for 43 assessable patients (95% confidence interval, 14% to 42%), including one complete remission (2%). Seventeen additional patients (39%) had stable disease, and fourteen (33%) progressed. The median time to progression was 5.9 months and the median overall survival was 13.2 months from the start of the chemotherapy. From the 297 cycles analyzed, hematologic toxicities per course were: leukopenia; grade I 26.6%, grade II 3.4%, and grade III 0.3%, thrombocytopenia; grade I 10.8%, grade II 3.0%, grade III 1.0%, and grade IV 0.3%. The most frequent nonhematologic adverse reactions were nausea/vomiting and peripheral neuropathy, which were rated as WHO grade II in 13 patients (49%) and 11 patients (22%), respectively.
CONCLUSION
This phase II study of oxaliplatin, 5-FU, and LV continuous infusion showed enhanced antitumor activity in patients with 5-FU-pretreated metastatic colorectal cancer. Overall toxicity was acceptable; neurotoxicity and bone marrow suppression constituted the dose-limiting side effects.

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