Cancer Research and Treatment

Original Articles

Genitourinary cancer

A Multicenter Phase II Study of Modified FOLFIRINOX for First-Line Treatment for Advanced Urachal Cancer (ULTIMA; KCSG GU20-03): Inkeun Park, Jae Lyun Lee, Shinkyo Yoon, Sang Joon Shin, Seong-Hoon Shin, Jung Hoon Kim, Kwonoh Park, Hyo Jin Lee; Cancer Res Treat. 2026;58(1):284-291. Published online February 13, 2025; DOI: https://doi.org/10.4143/crt.2024.1231

Purpose
This study aimed to assess the efficacy and safety of first-line modified FOLFIRINOX in patients with advanced urachal cancer.
Materials and Methods
The ULTIMA trial (NCT04611724) is a single-arm, open-label, multicenter phase II study evaluating modified FOLFIRINOX (oxaliplatin 85 mg/m² over 2 hours, irinotecan 150 mg/m² over 1.5 hours, leucovorin 400 mg/m² over 2 hours, and 5-fluorouracil 2,400 mg/m² over 46 hours) plus prophylactic pegteograstim in patients with recurrent or metastatic urachal cancer every 2 weeks for up to 12 cycles, or until disease progression or unacceptable toxicity. The primary endpoint was the overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and the incidence of febrile neutropenia.
Results
Between April 2021 and November 2023, 21 patients with advanced urachal cancer were enrolled across five cancer centers. The median age was 50 years (range, 28 to 68 years), with 15 male patients. The most common metastatic site was the lung (47.6%), followed by lymph nodes (38.1%) and peritoneal seeding (33.3%). Two patients and 11 patients achieved a complete and partial response, respectively, yielding an ORR of 61.9%. The study met its primary endpoint in the first stage. With a median follow-up of 23.3 months, the median PFS was 9.3 months (95% confidence interval [CI], 6.7 to 11.9), and the median OS was 19.7 months (95% CI, 14.3 to 25.1). The treatment regimen was well tolerated, with no unexpected adverse events, and no instances of febrile neutropenia or grade 4 adverse events.
Conclusion
In this preliminary analysis of the ULTIMA trial, Modified FOLFIRINOX demonstrated a promising ORR and PFS in patients with advanced urachal cancer. Completing the full study is essential to confirm the potential role of this regimen in the management of advanced urachal cancer.

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Patient-derived d-MMR/MSI phenotype urachal cancer organoids for personalized drug screening
Kuangen Zhang, Xinyi Li, Zhenting Zhang, Ning Zhang, Xin Yao, Rong Liu
Frontiers in Oncology.2026;[Epub] CrossRef
Robotic Partial Cystectomy and Extended Pelvic Lymph Node Dissection for Node-Positive Urachal Adenocarcinoma in a 34-Year-Old Woman: A Case Report
Stefanie Herrmann, Christian Gilfrich, Stephan Siepmann, Julio Ruben Rodas Garzaro, Fabian Eder, Stephan Schleder, Philipp Aubele, Felix Keil, Matthias May, Anton Kravchuk
Current Oncology.2026; 33(4): 190. CrossRef
Metastatic urachal carcinoma treated with trifluridine/tipiracil and bevacizumab: a case report
Takafumi Kitazono, Taichi Isobe, Satoshi Nishiyori, Wataru Kusano, Kenro Tanoue, Tomoyasu Yoshihiro, Hirofumi Ohmura, Kyoko Yamaguchi, Mamoru Ito, Kenji Tsuchihashi, Koichi Akashi, Eishi Baba
International Cancer Conference Journal.2025; 14(3): 280. CrossRef
Urachal cancer: a clinical, diagnostic, and therapeutic update
Henning Reis, Tibor Szarvas, Gladell P. Paner
Current Opinion in Urology.2025;[Epub] CrossRef

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CXCL-13 Regulates Resistance to 5-Fluorouracil in Colorectal Cancer: Guolin Zhang, Xin Luo, Wei Zhang, Engeng Chen, Jianbin Xu, Fei Wang, Gaoyang Cao, Zhenyu Ju, Dongai Jin, Xuefeng Huang, Wei Zhou, Zhangfa Song; Cancer Res Treat. 2020;52(2):622-633. Published online December 31, 2019; DOI: https://doi.org/10.4143/crt.2019.593

Abstract PDF PubReader ePub

Purpose
5-Fluorouracil (5-Fu) is used as a conventional chemotherapy drug in chemotherapy for patients with advanced colorectal cancer, but many patients still suffer from treatment failure due to 5-Fu resistance. Emerging observations revealed the important role of chemokine (C-X-C motif) ligand 13 (CXCL-13) in tumor microenvironment and its relationship with prognosis in patients with colorectal cancer. This study is designed to reveal the important role of CXCL-13 in causing colorectal cancer resistance to 5-Fu.
Materials and Methods
CXCL-13 levels of patient's serum or cell culture supernatants were measured separately by enzyme-linked immunosorbent assay. In cell assays, cell viability is detected by Cell Counting Kit-8. Therefore, the recombinant human CXCL-13 was used to simulate its high expression in cells while its antibody and siRNA were used to reduce CXCL-13 expression in cells.
Results
In this study, we demonstrated that CXCL-13 is associated with 5-Fu resistance by culture medium exchange experiments and cytokine arrays of colorectal cancer resistant and nonresistant cells. Clinical studies showed that CXCL-13 is highly expressed in the serum of 5-Fu–resistant patients. High levels of serum CXCL-13 also predict a worse clinical outcome. The addition of recombinant CXCL-13 cytokine resulted in 5-Fu resistance, while its antibody overcame 5-Fu resistance, and knockdown of CXCL-13 expression by siRNA also reduced 5-Fu resistance, which can be saved by added recombination CXCL-13.
Conclusion
These results not only identify a CXCL-13 mediated 5-Fu resistance mechanism but also provide a novel target for 5-Fu–resistant colorectal cancer in prevention and treatment strategies.

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S-1–Induced Lacrimal Drainage Obstruction and Its Association with Ingredients/Metabolites of S-1 in Tears and Plasma: A Prospective Multi-institutional Study: Namju Kim, Jin Won Kim, Je-Hyun Baek, Jin-Soo Kim, Ho-Kyung Choung, Tae-Yong Kim, Kyung-Hun Lee, Yung-Jue Bang, Sang In Khwarg, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim, Jae-Yong Chung, Soyeon Ahn, Keun-Wook Lee; Cancer Res Treat. 2018;50(1):30-39. Published online February 27, 2017; DOI: https://doi.org/10.4143/crt.2016.569

Abstract PDF Supplementary Material PubReader ePub

Purpose
This prospective study was conducted to determine the incidence of lacrimal drainage obstruction (LDO) during S-1 chemotherapy and evaluate the association between the development of LDO and the concentrations of ingredients/metabolites of S-1 in tears and plasma.
Materials and Methods
A total of 145 patients with gastric cancer who received adjuvant S-1 therapy were enrolled. Ophthalmologic examinations were performed regularly during S-1 chemotherapy. Concentrations of tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP), and 5-fluorouracil at steady-state trough level were measured in both tears and plasma.
Results
Fifty-three patients (37%) developed LDO. The median time to the onset of LDO was 10.9 weeks, and LDO developed most frequently in the nasolacrimal duct. Univariable analyses revealed that an older age (≥ 70 years), creatinine clearance rate (Ccr) < 80 mL/min, 5-fluorouracil concentration in plasma ≥ 22.3 ng/mL (median), CDHP concentration in plasma ≥ 42.0 ng/mL (median), and tegafur concentration in tears ≥ 479.2 ng/mL (median) were related to increased development of LDO. Multivariable analysis indicated that a high plasma 5-fluorouracil concentration was predictive of increased development of LDO (hazard ratio, 2.02; p=0.040), along with older age and decreased Ccr. Patients with LDO also developed S-1–related non-hematologic toxicity more frequently than those without LDO (p=0.016).
Conclusion
LDO is a frequent adverse event during S-1 chemotherapy. An older age, decreased Ccr, and high plasma 5-fluorouracil concentration were found to be independent risk factors for LDO. The high incidence of LDO warrants regular ophthalmologic examination and early intervention in patients receiving S-1 therapy.

Citations

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MTHFR polymorphism is associated with increased adverse events and poor clinical outcomes in gastric cancer patients with adjuvant S-1 chemotherapy
Minsu Kang, Jin Won Kim, Ju Hyun Lee, Lyoung Hyo Kim, Woochan Park, So Hyun Kang, Young Suk Park, Ji-Won Kim, Hyeon Jeong Oh, Sang-Hoon Ahn, Yun-Suhk Suh, Do Joong Park, Hye Seung Lee, Hyung-Ho Kim, Keun-Wook Lee
Scientific Reports.2026;[Epub] CrossRef
Ocular complication induced by anticancer drug S-1: association with drug concentrations in tears
Masakazu Yamada, Tomoyuki Kamao, Atsushi Shiraishi, Jo Sakai, Yuichi Ohashi, Masashi Mimura, Yoshitsugu Inoue, Kazuyoshi Ohtomo, Tai-ichiro Chikama, Chika Miyazaki, Yuka Hosotani
Japanese Journal of Ophthalmology.2025; 69(3): 447. CrossRef
Efficacy and Safety of a 3‐Weekly TS‐1 Adjuvant Regimen in Advanced Gastric Cancer: A Pilot Study
Jihong Bae, Joo‐Hwan Park, Young Saing Kim, Hee Kyung Ahn, Eun Kyung Cho, Dong Bok Shin, Ji‐Hyeon Park, Jun‐Young Yang, Woon Kee Lee, Sun Jin Sym
Cancer Medicine.2025;[Epub] CrossRef
Comparing Analyte Concentrations in Paired Tear Fluid and Blood Samples
Yutong Wang, Li Liang, Rudy M. M. A. Nuijts, Marlies Gijs
Current Eye Research.2025; : 1. CrossRef
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Shubin Li, Xuebin Peng, MinJie Wang, Wenqian Wang, Yuye Liu, Qian Yang, Makoto Ozawa
Transboundary and Emerging Diseases.2024;[Epub] CrossRef
Nasolacrimal Duct Obstruction in the Patients Receiving Treatment for Cancer
Vasily D. Yartsev, Eugenia L. Atkova
International Ophthalmology Clinics.2023; 63(3): 137. CrossRef
Obstrução lacrimal pós-tratamento oncológico: revisão de literatura
Camilla Duarte Silva, Fabricio Lopes da Fonseca, Juliana Mika Kato, Suzana Matayoshi
Revista Brasileira de Oftalmologia.2022;[Epub] CrossRef
A Case of Nasolacrimal Duct Obstruction During S-1 Treatment For Breast Cancer
Hisataka Ominato, Michihisa Kono, Hidekiyo Yamaki, Takumi Kumai, Miki Takahara, Akihiro Katada, Tatsuya Hayashi
Practica Oto-Rhino-Laryngologica.2022; 115(6): 503. CrossRef
Corneal nerve changes following treatment with neurotoxic anticancer drugs
Jeremy Chung Bo Chiang, David Goldstein, Susanna B. Park, Arun V. Krishnan, Maria Markoulli
The Ocular Surface.2021; 21: 221. CrossRef
The impact of anticancer drugs on the ocular surface
Jeremy Chung Bo Chiang, Ilyanoon Zahari, Maria Markoulli, Arun V. Krishnan, Susanna B. Park, Annalese Semmler, David Goldstein, Katie Edwards
The Ocular Surface.2020; 18(3): 403. CrossRef
Pharmacokinetics of S-1 monotherapy in plasma and in tears for gastric cancer patients
Hirofumi Yasui, Takeshi Kawakami, Hiroya Kashiwagi, Keita Mori, Katsuhiro Omae, Jun Kasai, Kunihiro Yoshisue, Masahiro Kawahira, Takahiro Tsushima, Nozomu Machida, Akira Fukutomi, Ken Yamaguchi
International Journal of Clinical Oncology.2019; 24(6): 660. CrossRef

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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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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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Nucleotide Excision Repair and Response and Survival to Chemotherapy in Colorectal Cancer Patients
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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A prognostic analysis of 895 cases of stage III colon cancer in different colon subsites
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TRAP1 revisited: Novel localizations and functions of a ‘next-generation’ biomarker (Review)
MARIA ROSARIA AMOROSO, DANILO SWANN MATASSA, LORENZA SISINNI, GIACOMO LETTINI, MATTEO LANDRISCINA, FRANCA ESPOSITO
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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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Alejandro Schcolnik-Cabrera, Mandy Juárez, Bernardo Oldak, Mayra Cruz-Rivera, Ana Flisser, Alfonso Dueñas-González, Vinnitsa Buzoianu-Anguiano, Sandra Orozco-Suarez, Fela Mendlovic
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Oxaliplatin plus leucovorin and 5-fluorouracil (FOLFOX-4) as a salvage chemotherapy in heavily-pretreated platinum-resistant ovarian cancer
Vincenza Conteduca, Giorgia Gurioli, Lorena Rossi, Emanuela Scarpi, Cristian Lolli, Giuseppe Schepisi, Alberto Farolfi, Delia De Lisi, Valentina Gallà, Salvatore Luca Burgio, Cecilia Menna, Andrea Amadori, Lorena Losi, Dino Amadori, Maria Paola Costi, Ugo
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An-Jen Chiang, Min-Yu Chen, Chia-Sui Weng, Hao Lin, Chien-Hsing Lu, Peng-Hui Wang, Yu-Fang Huang, Ying-Cheng Chiang, Mu-Hsien Yu, Chih-Long Chang
Journal of Gynecologic Oncology.2017;[Epub] CrossRef
Mucinous ovarian cancer: A therapeutic review
Wen Xu, Jack Rush, Kirsty Rickett, Jermaine I.G. Coward
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Gemcitabine–oxaliplatin (GEMOX) for epithelial ovarian cancer patients resistant to platinum-based chemotherapy
Mohamed Elshebeiny, Walid Almorsy
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The efficacy and safety of Oxaliplatin-Vinorelbine as a second-line chemotherapy combination in patients with platinum-resistant pretreated epithelial ovarian cancer: A retrospective study
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Nusrat Bano, Rahila Najam, Faaiza Qazi, Ahmed Mateen
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Predictive Value of In Vitro Adenosine Triphosphate-Based Chemotherapy Response Assay in Advanced Gastric Cancer Patients Who Received Oral 5-Fluorouracil after Curative Resection: Ji Hyun Lee, Min-Chan Kim, Sung Yong Oh, Hyuk-Chan Kwon, Sung-Hyun Kim, Kyung A Kwon, Suee Lee, Jin Sook Jeong, Seok-Reyol Choi, Hyo-Jin Kim; Cancer Res Treat. 2011;43(2):117-123. Published online June 30, 2011; DOI: https://doi.org/10.4143/crt.2011.43.2.117

Abstract PDF PubReader ePub

PURPOSE
To assess the usefulness of adenosine triphosphate-based chemotherapy response assay (ATP-CRA) results in advanced gastric cancer patients receiving adjuvant chemotherapy.
MATERIALS AND METHODS
Sixty-two patients underwent curative surgical resection between January, 2006 and December, 2008. Their highly purified surgical specimens were evaluated by ATP-CRAs. Of the 62, 49 had successful assay results and they received either oral 5-fluorouracil or other chemotherapies. We retrospectively analyzed data for 24 patients who were treated with oral 5-fluorouracil and whose assays were successful.
RESULTS
The median observation time was 24.6 months (range, 10.1 to 40.9 months). The median treatment time was 11.2 months (range, 1.2 to 17.7 months). The median age was 66 years (range, 30 to 81 years). Patients were grouped into sensitive- and resistant-groups according to adenosine triphosphate-based chemotherapy response results for fluorouracil. The sensitive-group showed a significantly longer time to relapse (not reached in the sensitive-group vs. 24.8 months in the resistant-group, p=0.043) and longer overall survival compared to the resistant-group (not reached in the sensitive-group vs. 35.7 months in the resistant-group, p=0.16, statistically insignificant).
CONCLUSION
Patients who receive curative surgical resection significantly benefit from sensitive adjuvant chemotherapy according to ATP-CRA results for time to relapse.

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Young-Rok Kim, Kieun Bae, Ja-Young Lee, Soon-Wuk Jeong, Hun-Young Yoon, Hyun-Jung Han, Jae-Eun Hyun, Aryung Nam, Ji-Hwan Park, Kyong-Ah Yoon, Jung-Hyun Kim
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In Vitro Adenosine Triphosphate-Based Chemotherapy Response Assay as a Predictor of Clinical Response to Fluorouracil-Based Adjuvant Chemotherapy in Stage II Colorectal Cancer
Hye Youn Kwon, Im-kyung Kim, Jeonghyun Kang, Seung-Kook Sohn, Kang Young Lee
Cancer Research and Treatment.2016; 48(3): 970. CrossRef
Clinical correlation between <i>in vitro</i> chemoresponse assay and first line chemotherapy for metastatic colorectal cancer patients
Sang Hun Jung, So Hyun Kim, Jae Hwang Kim
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Purinergic signalling in the gastrointestinal tract and related organs in health and disease
Geoffrey Burnstock
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Establishment of 5-fluorouracil-resistant oral squamous cell carcinoma cell lines with epithelial to mesenchymal transition changes
KOJI HARADA, TARANNUM FERDOUS, YOSHIYA UEYAMA
International Journal of Oncology.2014; 44(4): 1302. CrossRef
Purinergic signalling and cancer
Geoffrey Burnstock, Francesco Di Virgilio
Purinergic Signalling.2013; 9(4): 491. CrossRef
Establishment and characterization of two 5-fluorouracil-resistant hepatocellular carcinoma cell lines
KAZUYA UCHIBORI, ATSUSHI KASAMATSU, MASAHIKO SUNAGA, SATOSHI YOKOTA, TOMOYA SAKURADA, ERIKO KOBAYASHI, MASAHARU YOSHIKAWA, KATSUHIRO UZAWA, SHIRO UEDA, HIDEKI TANZAWA, NOBUNORI SATO
International Journal of Oncology.2012; 40(4): 1005. CrossRef

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A Phase II Trial of Paclitaxel, 5-fluorouracil (5-FU) and Cisplatin in Patients with Metastatic or Recurrent Gastric Cancer: Gun Hi Kang, Gwang Sil Kim, Hyo Rak Lee, Young Jin Yuh, Sung Rok Kim; Cancer Res Treat. 2008;40(3):106-110. Published online September 30, 2008; DOI: https://doi.org/10.4143/crt.2008.40.3.106

Abstract PDF PubReader ePub

Purpose

We wanted to assess the effectiveness and safety of combination chemotherapy with paclitaxel, 5-fluorouracil (5-FU) and cisplatin for treating advanced gastric cancer.

Materials and Methods

Patients with metastatic or recurrent gastric cancer were entered into this study. Paclitaxel at a dose of 135 mg/m² on day 1, 5-FU 1 g/m²/day in a 24 hour continuous infusion from day 1 to day 4 and cisplatin 60 mg/m² on day 1 were administered. This regimen was repeated every 3 weeks.

Results

A total of 34 patients were enrolled in this study. Among them, 33 patients were finally evaluable for their response. 17 (51.5%) patients had a partial response (95% CI: 26.0~77.0%). The median duration of overall survival was 13.2 months. Grade 3 or 4 neutropenia and thrombocytopenia were observed in 15.2% and 1.1% of all the cycles, respectively. Grade 3 stomatitis and neurotoxicity were observed in 20.6% and 1.1% of all patients, respectively. Grade 4 non-hematologic toxicity was not observed.

Conclusions

The regimen of paclitaxel, 5-FU and cisplatin demonstrated activity and accepatable toxicity for treating metastatic gastric cancer.

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Intraperitoneal administration of biocompatible hyaluronic acid hydrogel containing multi-chemotherapeutic agents for treatment of colorectal peritoneal carcinomatosis
Jia Luo, ZhouXue Wu, Yun Lu, Kang Xiong, Qian Wen, Ling Zhao, BiQiong Wang, Yan Gui, ShaoZhi Fu
International Journal of Biological Macromolecules.2020; 152: 718. CrossRef
A Peptidic Thymidylate-Synthase Inhibitor Loaded on Pegylated Liposomes Enhances the Antitumour Effect of Chemotherapy Drugs in Human Ovarian Cancer Cells
Gaetano Marverti, Gaia Gozzi, Eleonora Maretti, Angela Lauriola, Leda Severi, Francesca Sacchetti, Lorena Losi, Salvatore Pacifico, Stefania Ferrari, Glauco Ponterini, Eliana Leo, Maria Paola Costi, Domenico D’Arca
International Journal of Molecular Sciences.2020; 21(12): 4452. CrossRef
Triplet combination with paclitaxel, cisplatin and 5-FU is effective in metastatic and/or recurrent nasopharyngeal carcinoma
Cui Chen, Feng-hua Wang, Xin An, Hui-yan Luo, Zhi-qiang Wang, Ying Liang, Le Zhang, Yu-hong Li
Cancer Chemotherapy and Pharmacology.2013; 71(2): 371. CrossRef
Targeted therapy for gastric cancer—current status
Jan Kulig, Piotr Kołodziejczyk, Piotr Kulig, Janusz Legutko
Journal of Oncology Pharmacy Practice.2013; 19(1): 75. CrossRef
Targeted Therapies for Gastric Cancer
Jaclyn Yoong, Michael Michael, Trevor Leong
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Down-Regulation of Human Epidermal Growth Factor Receptor 2/neu Oncogene by Corosolic Acid Induces Cell Cycle Arrest and Apoptosis in NCI-N87 Human Gastric Cancer Cells
Myung Sun Lee, Eun Young Cha, Phuong Thien Thuong, Ji Yeon Kim, Moon Sang Ahn, Ji Young Sul
Biological and Pharmaceutical Bulletin.2010; 33(6): 931. CrossRef
Efficacy and feasibility of radiofrequency ablation for liver metastases from gastric adenocarcinoma
Hye Ryun Kim, Seong Ha Cheon, Kwang-Hun Lee, Jung Ryun Ahn, Hei-Cheul Jeung, Sung Sook Lee, Hyun Cheol Chung, Sung Hoon Noh, Sun Young Rha
International Journal of Hyperthermia.2010; 26(4): 305. CrossRef

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A Phase II Study of Leucovorin, 5-FU and Docetaxel Combination Chemotherapy in Patients with Inoperable or Postoperative Relapsed Gastric Cancer: Kwang-Sun Lee, Ha-Yeon Lee, Eun-Kyung Park, Joung-Soon Jang, Sang-Jae Lee; Cancer Res Treat. 2008;40(1):11-15. Published online March 31, 2008; DOI: https://doi.org/10.4143/crt.2008.40.1.11

Abstract PDF PubReader ePub

Purpose

To estimate the effect and toxicity of bimonthly low-dose leucovorin (LV) and fluorouracil (5-FU) bolus plus continuous infusion(LV5FU2) with docetaxel combination chemotheraphy in patients with inoperable or postoperative relapsed gastric cancer.

Materials and Methods

Total 27 patients are enrolled in this study. LV 20 mg/m² (bolus), 5FU 400 mg/m² (bolus), 5-FU 600 mg/m² (24-hour continuous infusion) on day 1, 2, 15, and 16, docetaxel 60 mg/m² (1-hour infusion) on day 15 every 4 weeks.

Results

Total of 141 cycles were administered and response rate were 36.8% with 2 complete response (10.5%) and 5 partial response (26.3%) in 19 evaluable patients. The median response duration is 8.1 months (95% CI, 4.0~12.1). The median progression-free survival time is 6.7 months (95% CI, 5.0~8.5) and the median overall survival time is 11.9 months (95% CI, 4.8~19.1). The grade 3-4 toxcity of neutropenia (24.8%) and anemia (11.3%), neutropenic fever (2.8%) is observed. The grade 1 toxcity of injection site reaction is observed all patients and the grade 1-2 toxcity of alopecia is observed 60%.

Conclusions

LV5FU2 with docetaxel combination chemotheraphy is effective and tolerable in patients with inoperable or postoperative relapsed gastric cancer.

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Neoadjuvant camrelizumab and apatinib combined with chemotherapy versus chemotherapy alone for locally advanced gastric cancer: a multicenter randomized phase 2 trial
Jian-Xian Lin, Yi-Hui Tang, Hua-Long Zheng, Kai Ye, Jian-Chun Cai, Li-Sheng Cai, Wei Lin, Jian-Wei Xie, Jia-Bin Wang, Jun Lu, Qi-Yue Chen, Long-Long Cao, Chao-Hui Zheng, Ping Li, Chang-Ming Huang
Nature Communications.2024;[Epub] CrossRef
Docetaxel and capecitabine for advanced gastric cancer: investigating dose-dependent efficacy in two patient cohorts
P C Thuss-Patience, A Kretzschmar, Y Dogan, F Rothmann, I Blau, I Schwaner, K Breithaupt, D Bichev, M Grothoff, C Grieser, P Reichardt
British Journal of Cancer.2011; 105(4): 505. CrossRef

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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

A Pilot Study of Cisplatin, Irinotecan, Leucovorin and 5-fluorouracil (PILF) Combination Chemotherapy for Advanced Gastric Cancer: Se Hoon Park, Soo Yeon Jeon, Kwang Il Ko, Eunmi Nam, Soo-Mee Bang, Eun Kyung Cho, Dong Bok Shin, Jae Hoon Lee, Woon Ki Lee, Min Chung; Cancer Res Treat. 2006;38(3):121-125. Published online June 30, 2006; DOI: https://doi.org/10.4143/crt.2006.38.3.121

Abstract PDF PubReader ePub

Purpose

Irinotecan, in combination with leucovorin/5-fluorouracil (FU) or with cisplatin, is known to be active for treating advanced gastric cancer (AGC). This pilot study evaluated a novel three-drug combination of irinotecan, leucovorin/FU and cisplatin as a first-line treatment of AGC. The primary endpoint was to assess the feasibility in anticipation of conducting a larger phase II study.

Materials and Methods

Chemotherapy-naive AGC patients received irinotecan 150 mg/m² on day 1, and leucovorin 200 mg/m² and a 22-h infusion of FU 1000 mg/m² on days 1 and 2. Cisplatin 30 mg/m² was administered on day 2. Treatment was repeated every 2 weeks until disease progression or unacceptable toxicity.

Results

Of the 17 eligible patients, two patients had an ECOG performance status of 2 and their median age was 48 years (range: 31 to 69). A total of 117 chemotherapy cycles were delivered (median: 6, range: 1 to 12). The causes of treatment discontinuation were disease progression in 9 patients (53%), refusal (35%) and toxicity (12%). Although grade 3 or 4 neutropenia (41% of patients) was the major toxicity that required dose adjustments, only one episode of febrile neutropenia occurred. Grade 3 or 4 nausea and vomiting, diarrhea and fatigue were observed in 35%, 35% and 29% of patients, respectively. None of the patients died of toxicity during treatment. Of the 16 patients who were evaluable for response, 7 (44%) experienced a partial response.

Conclusion

This novel multi-drug combination was tolerated well in patients with AGC. Based on the encouraging efficacy and tolerability, a randomized phase II study is ongoing in this disease setting.

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Randomized phase II study of irinotecan, leucovorin and 5-fluorouracil (ILF) versus cisplatin plus ILF (PILF) combination chemotherapy for advanced gastric cancer
S.H. Park, E. Nam, J. Park, E.K. Cho, D.B. Shin, J.H. Lee, W.K. Lee, M. Chung, S.I. Lee
Annals of Oncology.2008; 19(4): 729. CrossRef

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A Phase II Study of Irinotecan, 5-Fluorouracil and Leucovorin for Treatment in Patients with Previously Untreated Advanced Colorectal Cancer: Sang-Byung Bae, Nam-Su Lee, Han-Jo Kim, Kyoung-Ha Kim, Hyun-Jung Kim, Chan-Kyu Kim, Kyu-Taeg Lee, Sung-Kyu Park, Jong-Ho Won, Dae-Sik Hong, Hee-Sook Park; Cancer Res Treat. 2006;38(2):72-77. Published online April 30, 2006; DOI: https://doi.org/10.4143/crt.2006.38.2.72

Abstract PDF PubReader ePub

Purpose

We prospectively conducted a non-randomized phase II trial to evaluate the efficacy and safety of combination irinotecan, leucovorin (LV) and 5-fluorouracil (FU) as a first-line regimen for treating patients with previously untreated advanced colorectal cancer (CRC).

Materials and Methods

Twenty-six previously untreated patients with advanced, recurrent or metastatic CRC were enrolled in this study. The patients received either irinotecan 180 mg/m² on day 1 with LV bolus of 200 mg/m² and FU bolus of 400 mg/m², and this was followed by FU continuous infusion of 600 mg/m² on day 1 and day 2 (the FOLFIRI regimen), or they were treated with LV bolus of 400 mg/m² and FU bolus of 400 mg/m² followed by FU continuous infusion of 2,400 mg/m² for 46 hours (the simplified FOLFIRI regimen), and these treatments were repeated every 2 weeks until disease progression.

Results

The objective response rate was 23.1% (6/26) respectively, for both treatments. The median time to progression was 5.3 months (range: 0.4~19.9), and the overall survival was 11.2 months (range: 0.5~52.3). The prognostic factor for longer survival was the Eastern Cooperative Oncology Group (ECOG) performance status (PS). The non-hematological toxicities were similar for both treatment groups, with more frequent grade ≥3 neutropenia being noted for the simplified FOLFIRI regimen.

Conclusion

The biweekly irinotecan based regimen was demonstrated to have a moderate antitumor activity with acceptable toxicity profiles, and the ECOG PS was the independent prognostic factor.

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Oncological Treatment-Related Fatigue in Oncogeriatrics: A Scoping Review
Louise André, Gabriel Antherieu, Amélie Boinet, Judith Bret, Thomas Gilbert, Rabia Boulahssass, Claire Falandry
Cancers.2022; 14(10): 2470. CrossRef
The use of high dose d,l-leucovorin in first-line bevacizumab+mFOLFIRI treatment of patients with metastatic colorectal cancer may enhance the antiangiogenic effect of bevacizumab
B. Budai, T. Nagy, I. Láng, E. Hitre
Angiogenesis.2013; 16(1): 113. CrossRef
Successful Treatment of Small-Cell Lung Cancer With Irinotecan in a Hemodialysis Patient With End-Stage Renal Disease
Dong Min Kim, Hyun Lee Kim, Choon Hae Chung, Chi Young Park
The Korean journal of internal medicine.2009; 24(1): 73. CrossRef

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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.

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Journal of Korean Medical Science.2007; 22(3): 400. CrossRef

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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.

Citations

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Phase I study of pevonedistat combined with capecitabine and oxaliplatin in patients with platinum-refractory advanced gastric cancer
Hirokazu Shoji, Daisuke Takahari, Akira Ooki, Hidekazu Hirano, Natsuko Okita, Kengo Nagashima, Jun Adachi, Kensei Yamaguchi, Ken Kato, Narikazu Boku
Scientific Reports.2025;[Epub] CrossRef
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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Thymidylate Synthase, Thymidine Phosphorylase, VEGF and p53 Protein Expression in Primary Colorectal Cancer for Predicting Response to 5-fluorouracil-based Chemotherapy: Myung-Ju Ahn, Jung-Hye Choi, Ho-Suk Oh, Young-Yeul Lee, In-Soon Kim, Il-Young Choi, Kang-Hong Lee, Kang-Won Song, Chan-Kum Park; Cancer Res Treat. 2005;37(4):216-222. Published online August 31, 2005; DOI: https://doi.org/10.4143/crt.2005.37.4.216

Abstract PDF PubReader ePub

Purpose

In the treatment of advanced metastatic colorectal cancer, several new agents, such as irinotecan and oxaliplatin, have been developed, which have improved both disease free and overall survivals. Among these agents, 5-fluorouracil (5-FU) still remains one of the most active agents, and the selection of patients who can benefit from 5-FU-based chemotherapy is still important, as those unlikely to benefit could be spared the harmful side effects. The expression levels of thymidylate synthase (TS), thymidine phosphorylase (TP) and p53 have been known to be associated with the clinical response to 5-FU-based therapy as well as the prognosis, and that of vascular endothelial growth factor (VEGF) is associated with poor survival.

Materials and Methods

The relationship between the expressions of TS, TP, VEGF and p53 in primary tumors, using immunohistochemistry, and the response of 45 metastatic colorectal cancer patients (M:F=25:20, median age 59 yrs) to 5-FU-based chemotherapy were evaluated.

Results

Thirty-seven patients were treated with 5-FU/LV/irinotecan (FOLFIRI) and 8 with 5-FU/LV/oxaplatin (FOLFOX). The overall response rate was 28.9% (13/45). When immunohistochemically analyzed with monoclonal antibodies against TS, TP, VEGF and p53, 55.6% of the patients (25/45) were positive for TS, 48.9% (22/45) for TP, 82.2% (37/45) for VEGF, and 80% (36/45) for p53. There was a significant difference in the intensity of TS expression between the clinical responders and non-responders (p=0.036). In terms of the staining pattern of TS expression, diffuse staining was correlated with a poor response (p=0.012) and poor survival (p=0.045). However, there was no correlation between the expressions of TP, VEGF or P53 and the response to chemotherapy.

Conclusion

These results suggest that the expression of TS in primary colorectal cancer might be an important prognostic factor for chemotherapy response and survival, and might be a useful therapeutic marker for the response of chemotherapy.

Citations

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Epigenetic Approaches to Overcome Fluoropyrimidines Resistance in Solid Tumors
Laura Grumetti, Rita Lombardi, Federica Iannelli, Biagio Pucci, Antonio Avallone, Elena Di Gennaro, Alfredo Budillon
Cancers.2022; 14(3): 695. CrossRef
Immunoexpression of TS, p53, COX2, EGFR, MSH6 and MLH1 biomarkers and its correlation with degree of differentiation, tumor staging and prognostic factors in colorectal adenocarcinoma: a retrospective longitudinal study
Wilson Roberto Batista, Gianni Santos, Flávia Maria Ribeiro Vital, Delcio Matos
Sao Paulo Medical Journal.2019; 137(1): 33. CrossRef
Thymidine phosphorylase expression and prognosis in colorectal cancer treated with 5‑fluorouracil‑based chemotherapy: A meta‑analysis
Jia Che, Lun Pan, Xiangling Yang, Zhiting Liu, Lanlan Huang, Chuangyu Wen, Aihua Lin, Huanliang Liu
Molecular and Clinical Oncology.2017;[Epub] CrossRef
Does anti-p53 antibody status predict for clinical outcomes in metastatic colorectal cancer patients treated with fluoropyrimidine, oxaliplatin, plus bevacizumab as first-line chemotherapy?
Hiroki Osumi, Eiji Shinozaki, Mitsukuni Suenaga, Yosuke Kumekawa, Mariko Ogura, Masato Ozaka, Satoshi Matsusaka, Keisho Chin, Noriko Yamamoto, Nobuyuki Mizunuma
BMC Cancer.2015;[Epub] CrossRef
Comparison of thymidine phosphorylase expression and prognostic factors in gallbladder and bile duct cancer
Hye Sung Won, Myung Ah Lee, Eun-Seon Chung, Dong-Goo Kim, Young Kyoung You, Tae Ho Hong, In-Seok Lee
BMC Cancer.2010;[Epub] CrossRef

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cDNA Microarray Analysis of Differential Gene Expression in Gastric Cancer Cells Sensitive and Resistant to 5-Fluorouracil and Cisplatin: Myung-Ju Ahn, Young-Do Yoo, Ki-Hwan Lee, Joon-Ik Ahn, Dong-Hyun Yu, Hye-Sook Lee, Ho-Suck Oh, Jung-Hye Choi, Yong-Sung Lee; Cancer Res Treat. 2005;37(1):54-62. Published online February 28, 2005; DOI: https://doi.org/10.4143/crt.2005.37.1.54

Abstract PDF PubReader ePub

Purpose

Gastric cancer is one of the most prevalent cancers worldwide. 5-fluorouracil (5-FU) and cisplatin are the most commonly used drugs for the treatment of gastric cancer. However, a significant number of tumors often fail to respond to chemotherapy.

Materials and Methods

To better understand the molecular mechanisms underlying drug resistance in gastric cancer the gene expression in gastric cancer cells, which were either sensitive or resistant to 5-FU and cisplatin, were examined using cDNA microarray analysis. To confirm the differential gene expression, as determined using the microarray, semiquantitative RT-PCR was performed on a subset of differentially expressed cDNAs.

Results

69 and 45 genes, which were either up-regulated (9 and 22 genes) or down-regulated (60 and 25 genes), were identified in 5-FU- and cisplatin-resistant cells, respectively. Several genes, such as adaptor-related protein complex 1 and baculoviral IAP repeat-containing 3, were up-regulated in both drug-resistant cell types. Several genes, such as the ras homolog gene family, tropomyosin, tumor rejection antigen, protein disulfide isomerase-related protein, melanocortin 1 receptor, defensin, cyclophilin B, dual specificity phosphatase 8 and hepatocyte nuclear factor 3, were down-regulated in both drugresistant cell types.

Conclusion

These findings show that cDNA microarray analysis can be used to obtain gene expression profiles that reflect the effect of anticancer drugs on gastric cancer cells. Such data may lead to the assigning of signature expression profiles of drug-resistant tumors, which may help predict responses to drugs and assist in the design of tailored therapeutic regimens to overcome drug resistance.

Citations

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Molecular classification and prediction in gastric cancer
Xiandong Lin, Yongzhong Zhao, Won-min Song, Bin Zhang
Computational and Structural Biotechnology Journal.2015; 13: 448. CrossRef
Identification of Differentially-Expressed Genes in Intestinal Gastric Cancer by Microarray Analysis
Shizhu Zang, Ruifang Guo, Rui Xing, Liang Zhang, Wenmei Li, Min Zhao, Jingyuan Fang, Fulian Hu, Bin Kang, Yonghong Ren, Yonglong Zhuang, Siqi Liu, Rong Wang, Xianghong Li, Yingyan Yu, Jing Cheng, Youyong Lu
Genomics, Proteomics & Bioinformatics.2014; 12(6): 276. CrossRef
Protein disulfide isomerase in redox cell signaling and homeostasis
Francisco R.M. Laurindo, Luciana A. Pescatore, Denise de Castro Fernandes
Free Radical Biology and Medicine.2012; 52(9): 1954. CrossRef

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Phase II Study of Irinotecan, 5-Fluorouracil, and Leucovorin in Relapsed or Metastatic Colorectal Cancer as First-line Therapy: Young-Woong Won, Young-Hyo Lim, Ho-Yong Park, Ho-Suk Oh, Jung-Hye Choi, Young-Yeul Lee, In-Soon Kim, Il-Young Choi, Myung-Ju Ahn; Cancer Res Treat. 2004;36(4):235-239. Published online August 31, 2004; DOI: https://doi.org/10.4143/crt.2004.36.4.235

Abstract PDF PubReader ePub

Background

The purpose of this study was to assess the efficacy and toxicity of biweekly irinotecan plus 5-fluorouracil (FU) and leucovorin (LV) in patients with relapsed or metastatic colorectal cancer.

Materials and Methods

Between March 2002 and May 2004, 24 patients with histologically confirmed relapsed or metastatic colorectal cancer were enrolled in this study. One chemotherapy cycle consisted of irinotecan 180 mg/m² on days 1 and 15; 5-FU 400 mg/m² bolus IV with 600 mg/m² by a 22 hour intravenous infusion on days 1, 2, 15 and 16; and leucovorin 20 mg/m² on days 1, 2, 15 and 16, every 4 weeks.

Results

The median age of the 24 was 57.5 years (range, 38~69). Their metastatic sites included: the liver (62.5%), lung (20.8%), peritoneum (16.7%), lymph node (12.5%), ovary (8.3%) and pelvis/vagina (8.3%). Twenty-two patients were evaluable for a response. Six and 7 patients achieved partial responses and stable diseases, respectively. The overall response rate was 27.3% (95% Confidence interval; 10.3~44.5%). The median follow-up duration for surviving patients was 14.7 months (range, 1.7~26.5). Median overall survival (OS) and 1-year OS rates were 19 months and 86.3%, respectively. Median response duration and median progression free survival were 7.47 and 5.57 months, respectively. A total of 83 cycles (median 4 cycles) were administered. The main non-hematologic toxicities were nausea/vomiting (44.5%/18.1%) and diarrhea (8.4%). The most common hematologic toxicity was NCI grade I/II anemia (31.3%) and grade I/II neutropenia was 10.8%. There was no life-threatening toxicity.

Conclusion

The results suggested that irinotecan, 5-FU and leucovorin combination chemotherapy in a biweekly schedule is a practical and tolerable treatment option in patients with advanced colorectal cancer.

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Delivery System and Nanozyme: Nanotechnology‐Based Natural Sources Promise New Approaches in Colorectal Cancer Management
Ghazala Muteeb, Rawan S. Elsharkawy, Ayda H. El‐Gouhari, Ghannimah Yousef Alghuwainem, Mohammad Aatif, Doaa S. R. Khafaga
Micro & Nano Letters.2026;[Epub] CrossRef
A Phase I Study of UGT1A1 *28/*6 Genotype-Directed Dosing of Irinotecan (CPT-11) in Korean Patients with Metastatic Colorectal Cancer Receiving FOLFIRI
Kyu-Pyo Kim, Yong Sang Hong, Jae-Lyun Lee, Kyun Seop Bae, Ho-Sook Kim, Jae-Gook Shin, Jung Shin Lee, Tae Won Kim
Oncology.2015; 88(3): 164. CrossRef
Effect of an Irinotencan, 5-Fluorouracil, and Leucovorin Combination Chemotherapy (FOLFIRI) in Metastatic Colorectal Cancer
Seung Hyun Lee, Byung Kwon Ahn, Sung Uhn Baek
Journal of the Korean Society of Coloproctology.2007; 23(5): 333. CrossRef
A Phase II Study of Irinotecan, 5-Fluorouracil and Leucovorin for Treatment in Patients with Previously Untreated Advanced Colorectal Cancer
Sang-Byung Bae, Nam-Su Lee, Han-Jo Kim, Kyoung-Ha Kim, Hyun-Jung Kim, Chan-Kyu Kim, Kyu-Taeg Lee, Sung-Kyu Park, Jong-Ho Won, Dae-Sik Hong, Hee-Sook Park
Cancer Research and Treatment.2006; 38(2): 72. CrossRef
Irinotecan, Continuous 5-Fluorouracil, and Low dose of Leucovorin (modified FOLFIRI) as First Line of Therapy in Recurrent or Metastatic Colorectal Cancer
Myung-Ah Lee, Jae-Ho Byun, Byoung-Young Shim, In-Sook Woo, Jin-Hyung Kang, Young Seon Hong, Kyung Shik Lee, Myung Gyu Choi, Suk Kyun Chang, Seong Taek Oh, Sung Il Choi, Doo Suk Lee
The Korean Journal of Internal Medicine.2005; 20(3): 205. CrossRef
Responsiveness of CPT-11 in Respect to hMLH1 and hMSH2 Protein Expression in the Primary Colorectal Cancer
In Ja Park, Hee Cheol Kim, Chang Sik Yu, Heung Moon Chang, Jea Hwan Lee, Jong Hoon Kim, Tae Won Kim, Jung Sun Kim, Jin Cheon Kim
Cancer Research and Treatment.2004; 36(6): 360. CrossRef

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Efficacy of Postoperative Concurrent Chemoradiation for Resectable Rectal Cancer: A Single Institute Experience: Joong Bae Ahn, Hee Chul Chung, Nae Choon Yoo, Jae Kyung Roh, Nam Kyu Kim, Chang Ok Suh, Gwi Eon Kim, Jin Sil Seong, Woong Ho Shim, Hyun Cheol Chung; Cancer Res Treat. 2004;36(4):228-234. Published online August 31, 2004; DOI: https://doi.org/10.4143/crt.2004.36.4.228

Abstract PDF PubReader ePub

Purpose

For patients with Dukes' stage B and C rectal cancer, surgery followed by adjuvant chemoradiotherapy is considered to be the standard treatment. However, the drugs used in combination with 5-fluorouracil (5-FU), the method of administration, duration of adjuvant therapy and the frequencies of administration presently remain controversial topics. We investigated (1) the efficacy and safety of adjuvant radiotherapy and 5-FU/leucovorin (LV) chemotherapy for patients who had undergone curative resection and (2) the effect of dose related factors of 5-FU on survival.

Materials and Methods

130 rectal cancer patients with Dukes' B or C stage disease who were treated with curative resection were evaluated. The adjuvant therapy consisted of two cycles of 5-FU/LV chemotherapy followed by pelvic radiotherapy with chemotherapy, and then 4~10 more cycles of the same chemotherapy regimen were delivered based on the disease stage. The cumulative dose of 5-FU per body square meter (BSA), actual dose intensity and relative dose intensity were obtained. The patients were divided into two groups according to the median value of each factor, and the patients' survival rates were compared.

Results

With a median follow-up duration of 52 months, the 5-year disease-free survival and overall survival rates of 130 patients were 57% and 73%, respectively. Locoregional failure occurred in 17 (13%) of the 130 patients, and the distant failure rate was 27% (35/130). The chemotherapy related morbidity was minimal, and there was no mortality for these patients. The cumulative dose of 5-FU/BSA had a significant effect on the 5-year overall survival for Dukes' C rectal cancer patients (p=0.03). Multivariate analysis demonstrated that only the performance status affected the 5-year overall survival (p=0.003).

Conclusion

An adjuvant therapy of radiotherapy and 5-FU/LV chemotherapy is effective and tolerable for Dukes' B and C rectal cancer patients. A prospective, multicenter, randomized study to evaluate the effects of the cumulative dose of 5-FU/BSA on survival is required.

Citations

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Seven low-mass ions in pretreatment serum as potential predictive markers of the chemoradiotherapy response of rectal cancer
Kangsan Roh, Seung-Gu Yeo, Byong Chul Yoo, Kyung-Hee Kim, Sun Young Kim, Min-Jeong Kim
Anti-Cancer Drugs.2016; 27(8): 787. CrossRef
A 19-Gene expression signature as a predictor of survival in colorectal cancer
Nurul Ainin Abdul Aziz, Norfilza M. Mokhtar, Roslan Harun, Md Manir Hossain Mollah, Isa Mohamed Rose, Ismail Sagap, Azmi Mohd Tamil, Wan Zurinah Wan Ngah, Rahman Jamal
BMC Medical Genomics.2016;[Epub] CrossRef
Safety of Early Chemotherapy after a Laparoscopic Colorectal Cancer Resection: A Case-Control Study
Seung Ho Shin, Sun-Il Lee, Dong-Jin Choi, Si-Uk Woo, Jin Kim, Byung-Wook Min, Hong-Young Moon, Seon Hahn Kim
Journal of the Korean Society of Coloproctology.2009; 25(6): 429. CrossRef

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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.

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Genetic Predictors of Resistance and Survival in Oxaliplatin-Treated Iraqi Patients with Colorectal Cancer
Rehab Abd Almuttaleb Mohammed Jawad, Bahir Abdul Razzaq Mshimesh, Qasim Sharhan Al-Mayah, Fawaz Saad Al-Alloosh
Al-Rafidain Journal of Medical Sciences ( ISSN 2789-3219 ).2025; 8(2): 218. 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

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Combination Chemotherapy of Heptaplatin, Paclitaxel and 5-Fluorouracil in Patients with Advanced Gastric 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, Ho-Soon Choi, Sung-Joon Kwon; Cancer Res Treat. 2004;36(3):182-186. Published online June 30, 2004; DOI: https://doi.org/10.4143/crt.2004.36.3.182

Abstract PDF PubReader ePub

Purpose

To evaluate the efficacy and toxicity of heptaplatin, paclitaxel, and 5-fluorouracil combination chemotherapy in patients with advanced gastric cancer.

Materials and Methods

Between July 2002 and September 2003, nineteen patients were enrolled in this study. Paclitaxel 135 mg/m² iv on day 1, heptaplatin 400 mg/m² iv on day 2 and 5-fluorouracil 800 mg/m² on day 2~4 were administered and the regimen was repeated every 3 weeks.

Results

The median age of the patients was 60 years (range: 32~74) and the most common sites of metastasis were liver and lymph nodes. In the 16 evaluated patients, the overall response rate was 43.8%, but this was without any complete response. The median time to disease progression was 3.93 months (range: 0.26~8.1) and the median response duration for the 7 responding patients was 3.83 months (range: 1.48~6.07). The median overall survival for 19 patients was 7.01 months (range: 0.26~17.44). A median of 3 cycles (range: 1~7) and a total of 65 cycles were administered and evaluated for toxicity. The most common hematologic toxicities were NCI grade I/II anemia (47.7%), neutropenia (9.2%) and thrombocytopenia (6.2%). The most common non-hematologic toxicities more than grade II were nausea/vomiting (30.8%/9.2%). One elderly patient with ECOG 2 had a life-threatening complication of pneumonia.

Conclusion

The combination of heptaplatin, paclitaxel, and 5-fluorouracil showed significant activity and favorable toxicity profiles in patients with advanced gastric cancer. However, one elderly patient who had poor performance experienced a life-threatening toxicity/complication. Our results suggest that the efficacy of this combination chemotherapy can be maximized when administered to the patients with good performance status. Further studies with large numbers of patients and long-term follow-up study will be needed.

Citations

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Application of Approved Cisplatin Derivatives in Combination Therapy against Different Cancer Diseases
Dobrina Tsvetkova, Stefka Ivanova
Molecules.2022; 27(8): 2466. CrossRef
Synthesis of novel heptaplatin derivatives and evaluation of their ability to inhibit proliferation of cancer cell lines
W. Xu, D. C. Wang
Russian Journal of General Chemistry.2016; 86(4): 939. CrossRef

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Randomized Phase III Trial of Cisplatin, Epirubicin, Leucovorin, 5-Fluorouracil (PELF) Combination versus 5-fluorouracil Alone as Adjuvant Chemotherapy in Curative Resected Stage III Gastric Cancer: Jae Jin Lee, Si-Young Kim, Im sik Shin, Kyung Sam Cho, Hoong-Zae Joo, Choong Yoon, Yoon Wha Kim, Hwi Joong Yoon; Cancer Res Treat. 2004;36(2):140-145. Published online April 30, 2004; DOI: https://doi.org/10.4143/crt.2004.36.2.140

Abstract PDF PubReader ePub

Purpose

The combination of cisplatin, epirubicin, leucovorin and 5-fluorouracil (PELF) administration, as adjuvant chemotherapy after curative resection for gastirc cancer, was compared with 5-fluorouracil (5-FU) administration alone. This paper reports the results of a prospective randomized comparison of the two regimens, PELF and 5-FU.

Methods

From August 1996 to July 1999, 54 patients were selected subsequent to being diagnosed with stage III cancer after a curative resection for gastric cancer. The patients were stratified according to stage IIIA/IIIB and subtotal/total gastrectomy, and then they were randomized into each treatment group, i.e. the PELF or 5-FU alone groups.

Results

54 assessable patients were enrolled in this study: 28 received PELF and 26 received 5-FU alone. 12 patients relapsed in each group and the median follow-up duration was 42 months (range: 10~77 months). The overall survival rate and disease-free survival rate (DFS) were not significantly different between two groups, (5-year survival of PELF vs. 5-FU: 57% vs. 64%, 5-year DFS: 54% vs. 51%). The PELF combination was more toxic in terms of anemia, anorexia, nausea and diarrhea than the 5-FU.

Conclusions

This study showed that the PELF combination, as an adjuvant therapy for gastric cancer after a curative resection, was a less effective treatment, and it had more toxic effects than the 5-FU.

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Multidisciplinary treatment strategy for locally advanced gastric cancer: A systematic review
Kotaro Sugawara, Yoshikuni Kawaguchi, Yasuyuki Seto, Jean-Nicolas Vauthey
Surgical Oncology.2021; 38: 101599. CrossRef
The Efficacy and Safety of (Neo)Adjuvant Therapy for Gastric Cancer: A Network Meta-analysis
Tom van den Ende, Emil ter Veer, Mélanie Machiels, Rosa M. A. Mali, Frank A. Abe Nijenhuis, Laura de Waal, Marety Laarman, Suzanne S. Gisbertz, Maarten C. C. M. Hulshof, Martijn G. H. van Oijen, Hanneke W. M. van Laarhoven
Cancers.2019; 11(1): 80. CrossRef
Prognostic and Predictive Factors for the Curative Treatment of Esophageal and Gastric Cancer in Randomized Controlled Trials: A Systematic Review and Meta-Analysis
Tom van den Ende, Emil ter Veer, Rosa M. A. Mali, Mark I. van Berge Henegouwen, Maarten C. C. M. Hulshof, Martijn G. H. van Oijen, Hanneke W. M. van Laarhoven
Cancers.2019; 11(4): 530. CrossRef
COMplot, A Graphical Presentation of Complication Profiles and Adverse Effects for the Curative Treatment of Gastric Cancer: A Systematic Review and Meta-Analysis
Tom van den Ende, Frank A. Abe Nijenhuis, Héctor G. van den Boorn, Emil ter Veer, Maarten C. C. M. Hulshof, Suzanne S. Gisbertz, Martijn G. H. van Oijen, Hanneke W. M. van Laarhoven
Frontiers in Oncology.2019;[Epub] CrossRef
Comparative effectiveness of adjuvant treatments for resected gastric cancer: a network meta-analysis
Zhaolun Cai, Yiqiong Yin, Yuan Yin, Chaoyong Shen, Jian Wang, Xiaonan Yin, Zhixin Chen, Ye Zhou, Bo Zhang
Gastric Cancer.2018; 21(6): 1031. CrossRef
Current challenges of metastatic breast cancer
Bora Lim, Gabriel N. Hortobagyi
Cancer and Metastasis Reviews.2016; 35(4): 495. CrossRef
Management of Gastroesophageal Junction Tumors
Matthew P. Fox, Victor van Berkel
Surgical Clinics of North America.2012; 92(5): 1199. CrossRef

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Gemcitabine and Infusional 5-Fluorouracil in Advanced Pancreatic Cancer: A Clinical Benefit Response-Oriented Phase II Study: Jung Hye Choi, Myung Ju Ahn, Seock Ah Im, Bong Seog Kim, Ho Suk Oh, Heung Woo Lee, Yeung Chul Mun, Chu Myung Seong, Soon Nam Lee, Young Yeul Lee, Il Young Choi, In Soon Kim; Cancer Res Treat. 2003;35(3):213-217. Published online June 30, 2003; DOI: https://doi.org/10.4143/crt.2003.35.3.213

Abstract PDF: PURPOSE
Gemcitabine and 5-fluorouracil (5-FU) are two compounds with reproducible activity against advanced pancreatic carcinomas. To evaluate the activity and feasibility of this combination chemotherapy, a multi-institutional phase II study was performed. MATERIALS AND METHODS: Twenty patients (male: female 15: 5, median age: 60.5 years), with histologically verified locally advanced or metastatic pancreatic carcinomas, were enrolled between April 2000 and March 2002. Gemcitabine was administered by intravenous injection at the doses of 1, 000 mg/m2 on days 1, 8 and 15, and 5-FU 800 mg/m2/day, was given by continuous intravenous infusion on days 1~5. The treatment was repeated every 4 weeks. The clinical benefit response (CBR) was a composite of the pain, Karnofsky performance status and body weight change measurement.
RESULTS
Nineteen of the twenty patients were assessable for response. The median follow-up duration was 4.6 months (0.4~15.2 months). Five patients achieved a partial response and eight a stable disease. The overall response rate was 25.0%. The CBR was assessable in 12 patients. The overall CBR was 41.7% (5/12). The median survival of all the patients was 8.0 months. Grade 3~4 toxicities included neutropenia (9.3%) and thrombocytopenia (5.3%). CONCLUSION: This study suggested that gemcitabine, combined with infusional 5-FU, was well tolerated, and produced modest antitumor activity and symptomatic relief in advanced pancreatic cancer patients.

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Retinoic Acid Enhances Drug-Induced Cell Death in Anticancer Drug-Resistant Cell Lines: Young Mi Whang, Yeul Hong Kim, Sang Won Shin, Byung Soo Kim, Jun Suk Kim, Young Do Yoo, Sun Hee Park; Cancer Res Treat. 2002;34(3):212-217. Published online June 30, 2002; DOI: https://doi.org/10.4143/crt.2002.34.3.212

Abstract PDF

PURPOSE
Retinoids (RA), a group of vitamin A derivatives, is known to be important for regulation of normal cellular growth and differentiation. RA treatment of various cancers resulted in cell growth inhibition and apoptosis. Therefore, the chemotherapeutic and chemopreventative activities of various types of tumor have been examined. Biological actions of RA are mediated through nuclear receptors, including the retinoic acid receptors (RARs) and retinoid X receptors (RXRs). In this study, we examined the effect of all-trans-retinoic acid (atRA) as an anticancer drug-sensitiser in cancer cell lines and in its drug- resistant cancer cell lines MATERIALS AND METGODS: Cells were maintained by RPMI 1640 medium containing 10% fetal bovine serum. Cells were treated with 1 micro M atRA for 48 h, then with the desired concentration of anticancer drug for 24 h. Cell viability was measured spectrophotometrically at 540 nm using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. Western blot analyses were performed with the desired antibodies.
RESULTS
We investigated if pre-treatment with atRA enhanced the drug-sensitivity of various cancer cell lines to either 5-fluorouracil, adriamycin, or cisplatin. 5-FU (SNU638-F2) and CDDP-resistant cell (SNU638-Cis) lines, from a Korean gastric cancer cell line (SNU638) and the ADR-resistant cells (AD600) was established from a colon cancer cell line (SW620). Treatment of each cell line, with 1 micro M atRA, prior to drug exposure resulted in enhanced cell death in these cell lines. Furthermore, the effect of atRA on growth inhibition, in each drug-resistant cell line, was more obvious than in their parent cell lines. Increased activity of Transglutaminase II (TgaseII) and cleavage of Poly (ADP-ribose) polymerase (PARP) were also observed (western blot analysis CONCLUSION: Based on our data, we suggest that atRA enhances anticancer drug-induced cell death and reverses the drug-sensitivity of the drug-resistant cancer cell lines.

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All-trans Retinoic Acid Sensitizes Epithelial Ovarian Cancer to PARP Inhibition after Exposure to Cisplatin
Bingjie Mei, Junyang Li, Dengfeng Wang, Lu Feng, Jianming Huang, Guonan Zhang
Molecular Cancer Therapeutics.2025; 24(3): 453. CrossRef

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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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5-Fluorouracil , Ifosfamide and Cisplatin ( FIP ) Combination Chemotherapy for Advanced Non - Small Cell Lung Cancer: Young II Seo, Yougn Suk Park, Jae Myung Lee, Jo Young Choi, Hyun Soo Kim, Byung Dong Cho, Yu Mi Seo, Yun Chang Han, Ho joong Kim, In Gyu Hyun, Ki Suk Shun, Keun Chil Park, Duk Jhe Shun; J Korean Cancer Assoc. 1995;27(2):284-292.

Abstract PDF: We conducted a phase II trial of combining 5-fluorouracil(5-FU), ifosfamide(IFM), and cisplating(DDP) in previously untreated patients with advanced, unresectable, non-small cell lung cancer(NSCLC). Each cycle consisted of 5-FU 100 mg/m i. v. days 1-5, IFM 1000 mg/m i. v. days 1-3 with mesna, and DDP 100 mg/m i. v. day 1. Cycles were repeated at 3 week intervals. Twenty eight patients were enralled. Age ranged from 36 to 73(median 57 yearsk 24 were male, 4 female. Eleven patients had stage IIIb disease and 17 stage IV. Two patients were not evaluable because of lost to follow up. None had a complete response, 13 patients(50%) had par- tial responses, 8(31%) had stable diseases, and 5(19%) had progressive disesses. The median response duration was 11.2 weeks; the median time to progression was l2 weeks. The overall median survival was 19 weeks(27.5 weeks for responders, 12.8 weeks for non-responders). Majar side effects were alopecia, nausea/vomiting and stomatitis, all of which were we11 tolerated and reversible. By univariate analysis, stage and performance status correlated with time to progression and overall survival time. In conclusion, FIP combination chemotherapy for patients with advanced, unresectable non- small cell lung cancer seems to be an effective and well-tolerated regimen.

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Adjuvant Chemotherapy with ' 5-Fluorouracil Plus Low - dose Leucovorin Following Surgical Resection of Stage 2 , 3 Colon Cancer: Je Hwan Lee, Tae Won Kim, Jong Soo Choi, Dai Young Zang, Ho Young Pyun, Sung Bae Kim, Sang We Kim, Cheol Won Suh, Kyoo Hyung Lee, Jung Shin Lee, Woo Kun Kim, Sang Hee Kim, Jin Cheon Kim, Suk Koo Kim; J Korean Cancer Assoc. 1995;27(5):846-857.

Abstract PDF: Obtivea: About seventy-five percent of the individuals with colon cancer will have a primary surgical resection with the hope of complete tumor eradication. Despite the high resectability rate and a general improvement in therapy, nearly half of all patients with colon cancer still die of metastatic tumor. Over the past three decades, many clinical studies have failed to demonstrate benefits from adjuvant therapy. Recently, new data from several studies have demonstrated delays in tumor recurrence and increases in survival for specific groups of patients. The objective of this study was to evaluate the effective- ness of 5-fluorouracil(5-FU) and low-dose leucovorin in reducing the recurrence rate and improving the survival of the patients with surgically resected colon cancer in stage II and III. Methods: One hundred and fifty six with surgically resected colon cancer in stage II and 1II from Nov 1989 to Dec 1993 were included in this study and were divided into two groups. First group(LF arm) included eighty five Patients who received combination chemotherapy of '5-FU and low-dose 1eucovorin' following resection of colon cancer, and second group(control arm) included seventy one patients who received only oral UFT or no adjuvant treatment. '5-FU and low-dose leucovorin' chemotherapy consisted of leucovorin 20 mg/m(2), intravenously, plus 5-FU 400 mg/m(2), intravenously, on days 1-5 every 4 weeks for 6 cycles. Results: I) There were significantly more recurrences and distant failure in control arm than LF arm. 2) The estimated 4-year disease-free survival was 82.5% in LF arm and 59.8% in control arm(p = 0.007). 3) The estimated 4-year overall survival was 94.3% in LF arm and 63.9% in control arm (p = 0.001). 4) The survival differences between LF arm and control arm were significant in stage II and III respectively. 5) Number of metastatic lymph nodes, histologic differentiation, and whether or not pa- tients received 5-FU/leucovorin chemotherapy, were each found to have prognostic significance. Concluslon: This study strongly suggests that 5-FU and low-dose leucovorin adjuvant chemotherapy is effective in patients with surgically resected stage II and III colon cancer.

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Neoadjuvant Chemotherapy with 5-Fluorouracil and Cisplatin for Locally Advanced Head and Neck Cancer: Ji Hoon Park, Hwan Suk Choi, Jeong Hee Kim, Si Young Kim, Hwi Joong Yoon, Kyung Sam Cho, Seong Eon Hong, Dong Mok Ryu, Hoe Young Ahn; J Korean Cancer Assoc. 1995;27(6):990-1002.

Abstract PDF: Background
The prognosis for patients with locally advanced head and neck cancer remains poor. In recent years, attempts at improving the poor survival rates have frquently focused on the initial use of chemotherapy followed by subsequent standard local therapy with surgery and radiation. Methods: Twenty-seven patients with previously untreated, locally advanced (stage III or IV) head and neck cancer were treated with 2 or 3 cycles of combination chemotherapy consisting of 5-fluorouracil infusion and cisplatin followed by operation or radiotherapy between January,1988 and March,1994. Results: 1) After the neoadjuvant FP chemotherapy, sixteen of 27 patients(59.2%) demonstrated an objective response, with one(3.7%) achieving a complete clinical response(CR) and fifteen(55.5%) a partial response(PR). After the definitive local therapy(DLT:operation or radiation therapy), 12(44.4%) patients had a CR and 12(44.4%) achieved PR, respectively with 88.8% overall response rates. 2) Twelve patients received operation and 15 patients received radiotherapy after the neoadjuvant chemotherapy. Among 12 patients who received operation, seven(58%) patients achieved curative resection with surgery and five(33%) patients a complete remission, seven patients(46.7%) a partial remission with radiotherapy. 3) The overall median survival of total 27 patients was 31 months. The median survival of the responders (median:54 months) to FP chemotherapy was not significantly prolonged compared with nonresponders(median:23 months). 4) Time to disease progression of the responders to definite local therapy was 19 months. 5) Leukopenia and thrombocytopenia were observed in 48%(grade I-III) and l0%(grade I- II) respectively. Nausea and vomiting were observed in all patients, but easily controlled. Alopecia, diarrhea, stomatitis and nephrotoxicity were observed infrequently. There were no treatment related fatalities. Conclusion: Neoadjuvant FP chemotherapy in patients with locally advanced head and neck cancer was tolerable, but did not improve the response rate and overall survival compared with previous other reports. The phase III randomized controlled prospective studies are warranted for the verification of this study

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The Combined Effects of 5 - Fluorouracil and Recombinant Interferon - gamma on Human gastric Cancinoma Cell Lines: Heung Tae Kim, Jae Gahb Park, Jin Pok Kim, Seong Hoe Park, Noe Kyeong Kim; J Korean Cancer Assoc. 1990;22(3):458-476.

Abstract PDF: Stomach cancer is a leading malignant disease in many countries. Conventional combination chernotherapy approaches to advanced gastric cancer only produce paitial response and there has been no impact on patient survival from these approaches as well. Of several promising new approaches the combination of interferon (IFN) and chemotherapeutic agents are now being made to improve the effectiveness for the treatment of cancer. Preclinical studies suggested that IFN may biochemically modulate the cellular uptake or metabolism of 5-fluorouracil (5-FU) resulting in s synergistic antitumor effect. Based on these data, Wadler reparted a promising result with combina- tion of 5-FU and IFN-alpha in patients with advanced colorectal carcinoma. This study was conducted to investigate the combined effects af 5-FU and recombinant IFN- gamma at cellular level against four gastric carcinoma cell lines (SNU-1, SNU-5, SNU-16, and NCI-NB7). We used a semiautomated tetrazolium-based colorimetric (MTT) assay for cytotoxicity and an isobologram analysis to evaluate the effect of the combination. The experiment was perfor- med three times on each of the three cell lines. Only two experirnents for SNU-16 and NCI-N87 showed supraadditivity (p< 0.02). On isobologram plotted by the mean value of three experiments for each cell line, supraadditivity was suggested for only SNU-16 (p = 0.055). In conclusion, our result did not document in vitro synergy between 5-FU and IFN-gamma for gastric carcinoma cell lines but additivity within clinically achievable dose range. Because in vivo immunomodulatory effect of IFN-gamma on host is more important rather than antiproliferative effect, the combination of 5-FU and IFN gamma is expected to improve the treatment of advanced gastric cancer.

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Significance of Serum Total Lactate Dehydrogenase ( LDH ) Level and Isoenzyma Patterns in Non - Hodgkin's Lymphoma as a Prognostic Factor: Jee Sook Hahn, Hyun Cheol Chung, Joo Hang Kim, Sun Ju Lee, Eun Hee Koh, Jae Kyung Roh, Hyon Suk Kim, Yun Woong Ko, Byung Soo Kim; J Korean Cancer Assoc. 1990;22(3):476-490.

Abstract PDF: Serum total lactate dehydrogenase (LDH) and LDH isoenzyme activities were studied in 33 cases w i th non-H odgk in's lymphom a to compare the cl inical significance of serological staging with these two serological markers to anatomical staging. Serum total LDH activity correlated with tumor burden as determined by clinical stage at presentation. Initially, LDH-3 was the major fraction of increment for the reflection of increased serum total LDH activity. With the increment of tumor burden (total LDH >200 IU/L), LDH-3 with additional LDH-4 fraction increased, which resulted in LDH-1/LDH-3 flipped pattern. These changes were normalized if complete remission state was induced with treatment. A high pretreatment LDH level (total LDH> 200 IU/L) correlated significantly to a decreased survival rate IP.0.01l> Furthermore, the flip pattern of LDH-I/LDH-3 isoenzyme at diagnosis showed a decreased survival rate (p<0.05), in which 4-year survival rate of patients with non-flipped pattern was 73.8%, comparable to 25.4%; of patients with flippd pattern. The 4-year survival rate of the low risk group Itotal LDH 200 IU/L with unftipped pattern: serological stage A) was 73g while 2-year survival rate of the high risk group (total LDH>200 IU/L withflipped pattern: serological stage D) was 0%, which showed a significant difference (p<0.05). Stepwise Cox regression analysis to identify the important prognostic factors among the serum total LDH, LDH1/LDH-3 flip, serological stage, anatomical stage, B symptoms, cell type, hepatos- plemomegaly, mediastinal mass reveated that the serological stage was the only prognostic factor. In conclusion, based on results of the multivariate analysis, we propose a new prognostic classification of patients with serological staging system in non-Hodgkins lymphoma. Furthermore, the reproducibility and therapeutic stratigies will be warranted.

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A Phase 2 Study on Combined 5 - Fluorouracil , Etoposide , Doxorubicin and Cisplatin ( F - EAP ) in Patients with Advanced Gastric Cancer: J Korean Cancer Assoc. 1994;26(1):9-16.

Abstract PDF: 5-Fluorouracil(5-FU), as a single agent, has a modest but reproducible activity against gastric cancer and continuous infusion of 5-FU is associated with less myelosuppresion. It has been reported that combination of etoposide, doxorubicin, and cisplatin(EAP) was very active in advanced gastric carcinoma with an overall response rate of 64% including 21% complete response from the German investigators. A phase II study of the combination of 5-FU infusion, etoposide, doxorubicin and cisplatin(F-EAP), which regimen has been demonstrated to have the different mechanisms of action and synergism between each of drugs in vitro and in vivo, was performed in attempts to evaluate the antitumor activity in patients with advanced gastric cancer. Fifty-five previously untreated patients with surgically unreasectable or metastatic advanced gastric adenocarcinoma were treated with 5-FU(800 mg/m, days 2, 3, and 4), etoposide(70 mg/m, days 2, 3, and 4), doxorubicin(30 mg/m, day 1), and cisplatin(60 mg/m(2), day 1) repeated every 26 days. Objective responses were observed in 14 of 47(30%) evaluable patients, and the median duration of response was 21 weeks(l3~60+ ). The median survival time of 47 evaluable patients was 40 weeks(16~62). F-EAP therapy was associated with mild myelosuppression. The common non-hematologic toxieities were nausea/vomiting(94%), mucositis(32%), peripheral neuropathy (15%), and infection(11%), but the majority of these toxicities were mild to moderate and well tolerated. These results suggest that F-EAP regimen has a modest antitumor activity in terms of response rate and duration of response, and is relatively well tolerated in advanced gastric cancer.

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