Cancer Research and Treatment

Original Article

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

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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
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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
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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
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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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Meta-Analysis

Irinotecan Monotherapy Versus Irinotecan-Based Combination as Second-Line Chemotherapy in Advanced Gastric Cancer: A Meta-Analysis: Yo-Han Cho, So Young Yoon, Soo-Nyung Kim; Cancer Res Treat. 2017;49(1):255-262. Published online May 18, 2016; DOI: https://doi.org/10.4143/crt.2015.452

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Purpose
A meta-analysis was conducted to examine the question of whether combination regimens are more effective than monotherapy as a second-line chemotherapy in advanced gastric cancer.
Materials and Methods
The MEDLINE and the EMBASE databases and the Cochrane Central Register for Controlled Trials were searched using appropriate keywords. Only randomized controlled trials were eligible.
Results
Taxane-based study is rare; thus, four irinotecan-based studies were finally included in the meta-analysis. Out of 661 patients, 331 patients were assigned to combination therapy and 330 to monotherapy. Cisplatin or fluoropyrimidine (S-1 or 5-fluorouracil) was used as a combination partner to irinotecan. The pooled hazard ratio (HR) for overall survival (OS) and for progression-free survival (PFS) was 0.938 (95% confidence interval [CI], 0.796 to 1.104; p=0.442) and 0.815 (95% CI, 0.693 to 0.958; p=0.013). In subgroup analysis according to previous exposure to a partner agent, the PFS benefit of combination was observed only in the partially exposed group (HR, 0.784; 95% CI, 0.628 to 0.980; p=0.032).
Conclusion
Second-line irinotecan-based combination was not associated with increased OS, but with PFS benefit, which seemed particularly significant for patients receiving combination with a new agent.

Citations

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Camptothecin and Its Derivatives from Traditional Chinese Medicine in Combination with Anticancer Therapy Regimens: A Systematic Review and Meta-Analysis
Paul O. Odeniran, Paradise Madlala, Nompumelelo P. Mkhwanazi, Mahmoud E. S. Soliman
Cancers.2024; 16(22): 3802. CrossRef
Results of the use of ramucirumab in combination with irinotecan and fluoropyrimidines in the second-line chemotherapy for disseminated gastric cancer
N. S. Besova, T. A. Titova, D. L. Stroyakovsky, E. V. Perminova, S. G. Bagrova, E. S. Obarevich, V. A. Gorbunova, E. V. Artamonova, I. S. Stilidi
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Ramucirumab as Second-Line Therapy in Metastatic Gastric Cancer: Real-World Data from the RAMoss Study
Maria Di Bartolomeo, Monica Niger, Giuseppe Tirino, Angelica Petrillo, Rosa Berenato, Maria Maddalena Laterza, Filippo Pietrantonio, Federica Morano, Maria Antista, Sara Lonardi, Lorenzo Fornaro, Stefano Tamberi, Elisa Giommoni, Alberto Zaniboni, Lorenza
Targeted Oncology.2018; 13(2): 227. CrossRef
Ocoxin oral solution® as a complement to irinotecan chemotherapy in the metastatic progression of colorectal cancer to the liver
Iera Hernandez-Unzueta, Aitor Benedicto, Elvira Olaso, Eduardo Sanz, Cristina Viera, Beatriz Arteta, Joana Márquez
Oncology Letters.2017; 13(6): 4002. CrossRef

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Original Articles

Randomized Phase II Study of Pemetrexed Versus Gefitinib in Previously Treated Patients with Advanced Non-small Cell Lung Cancer: Young Saing Kim, Eun Kyung Cho, Hyun Sun Woo, Junshik Hong, Hee Kyung Ahn, Inkeun Park, Sun Jin Sym, Sun Young Kyung, Shin Myung Kang, Jeong-Woong Park, Sung Hwan Jeong, Jinny Park, Jae Hoon Lee, Dong Bok Shin; Cancer Res Treat. 2016;48(1):80-87. Published online March 2, 2015; DOI: https://doi.org/10.4143/crt.2014.307

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Purpose
This study aimed to evaluate the efficacy and safety of pemetrexed versus gefitinib in patients with advanced non-small cell lung cancer (NSCLC) previously treated with chemotherapy. Materials and Methods Patients with advanced (stage IIIB or IV) or recurrent NSCLC were randomly assigned to receive either 500 mg/m² of pemetrexed intravenously every 3 weeks or gefitinib 250 mg/day orally. The primary end point was progression-free survival (PFS) at 6 months.
Results
A total of 95 patients were enrolled (47 for pemetrexed and 48 for gefitinib). Most patients were male (72%) and current/ex-smokers (69%), and 80% had non-squamous cell carcinoma. The epidermal growth factor receptor (EGFR) mutation status was determined in 38 patients (40%); one patient per each arm was positive for EGFRmutation. The 6-month PFS rates were 22% and 15% for pemetrexed and gefitinib, respectively (p=0.35). Both arms showed an identical median PFS of 2.0 months and a median overall survival (OS) of 8.5 months. In EGFR wild-type patients, higher response rate (RR) and longer PFS as well as OS were achieved via pemetrexed compared with gefitinib, although there were no significant differences (RR: 39% vs. 9%, p=0.07; median PFS: 6.6 months vs. 3.1 months, p=0.45; median OS: 29.6 months vs. 12.9 months, p=0.62). Toxicities were mild in both treatment arms. Frequently reported toxicities were anemia and fatigue for pemetrexed, and skin rash and anorexia for gefitinib. Conclusion Both pemetrexed and gefitinib had similar efficacy with good tolerability as second-line treatment in unselected patients with advanced NSCLC. However, pemetrexed is considered more effective than gefitinib for EGFR wild-type patients.

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Adverse event profiles of EGFR-TKI: network meta-analysis and disproportionality analysis of the FAERS database
Jing Shi, Xinya Liu, Mengjiao Gao, Jian Yu, Ting Chai, Yun Jiang, Jiawei Li, Yuanming Zhang, Li Wu
Frontiers in Pharmacology.2025;[Epub] CrossRef
A network meta-analysis of immunotherapy-based treatments for advanced nonsquamous non-small cell lung cancer
Himani Aggarwal, Kerigo Ndirangu, Katherine B Winfree, Catherine Elizabeth Muehlenbein, Emily Zhu, Vanita Tongbram, Howard Thom
Journal of Comparative Effectiveness Research.2023;[Epub] CrossRef
Toxicity profile of epidermal growth factor receptor tyrosine kinase inhibitors for patients with lung cancer: A systematic review and network meta-analysis
Yi Zhao, Bo Cheng, Zisheng Chen, Jianfu Li, Hengrui Liang, Ying Chen, Feng Zhu, Caichen Li, Ke Xu, Shan Xiong, Weixiang Lu, Zhuxing Chen, Ran Zhong, Shen Zhao, Zhanhong Xie, Jun Liu, Wenhua Liang, Jianxing He
Critical Reviews in Oncology/Hematology.2021; 160: 103305. CrossRef
Efficacy and Safety of Pemetrexed and Gefitinib in the Treatment of Non-Small-Cell Lung Cancer: A Meta-Analysis
Zhihao Zhang, Xiyong Wang, Huaiqing Xiao, Dongqiang Wu, Dongliang Zhang, Qun Yu, Linna Yuan, Tao Huang
Computational and Mathematical Methods in Medicine.2021; 2021: 1. CrossRef
A meta-analysis of the safety and effectiveness of pemetrexed compared with gefitinib for pre-treated advanced or metastatic NSCLC
Xiaoxin Lu, Shengshu Li, Weizong Chen, Dongyang Zheng, Yuzhu Li, Fang Li
Medicine.2020; 99(29): e21170. CrossRef
Pemetrexed versus Gefitinib as Second-line Treatment for Advanced Non-small Cell Lung Cancer: A Meta-analysis Based on Randomized Controlled Trials
Huiyu Wang, Zunjing Zhang, Feng Liu, Miaoying Zhou, Handi Lv
Pteridines.2019; 30(1): 171. CrossRef
Gefitinib for advanced non-small cell lung cancer
Esther HA Sim, Ian A Yang, Richard Wood-Baker, Rayleen V Bowman, Kwun M Fong
Cochrane Database of Systematic Reviews.2018;[Epub] CrossRef
Pneumonitis in advanced non-small-cell lung cancer patients treated with EGFR tyrosine kinase inhibitor: Meta-analysis of 153 cohorts with 15,713 patients
Chong Hyun Suh, Hye Sun Park, Kyung Won Kim, Junhee Pyo, Hiroto Hatabu, Mizuki Nishino
Lung Cancer.2018; 123: 60. CrossRef
Second-Line Treatment of NSCLC—The Pan-ErbB Inhibitor Afatinib in Times of Shifting Paradigms
Jens Köhler
Frontiers in Medicine.2017;[Epub] CrossRef

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Results of a Phase II Study to Evaluate the Efficacy of Docetaxel and Carboplatin in Metastatic Malignant Melanoma Patients Who Failed First-Line Therapy Containing Dacarbazine: Choong-kun Lee, Minkyu Jung, Hye Jin Choi, Hye Ryun Kim, Hyo Song Kim, Mi Ryung Roh, Joong Bae Ahn, Hyun Cheol Chung, Su Jin Heo, Sun Young Rha, Sang Joon Shin; Cancer Res Treat. 2015;47(4):781-789. Published online February 16, 2015; DOI: https://doi.org/10.4143/crt.2014.261

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Purpose
There is no standard second-line regimen for malignant melanoma patients with disease progression after first-line chemotherapy, and platinum-alkylating agents combined with paclitaxel have shown modest efficacy. Materials and Methods We conducted a phase II, open-label, single-arm study to test the efficacy of docetaxel combined with carboplatin for malignant melanoma patients who failed previous treatment with dacarbazine. Intravenous docetaxel (35 mg/m2 on days 1 and 8 of each cycle) and carboplatin (area under the curve 3 on days 1 and 8 of each cycle) was administered every 21 days. Primary end point was objective response rate (ORR).
Results
Thirty patients were enrolled in the study, and the median follow-up duration was 19.8 months. Among 25 per-protocol patients, there were three responders (1 with complete response and 2 with partial response) and 17 stable disease patients (ORR, 12.0%). Among the per-protocol population, the median progression-free survival (PFS) was 4.3 months and the median overall survival (OS) was 9.6 months. Uveal melanoma patients (n=9) showed the best prognosis compared to other subtypes (median PFS, 7.6 months; OS, 9.9 months). The most common grade 3 or 4 adverse event was neutropenia (n=15, 50.0%). Conclusion Docetaxel combined with carboplatin showed association with an acceptable safety profile and overall efficacy for patients with malignant melanoma who had progressed on chemotherapy containing dacarbazine.

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A Phase 1 study of ADI‐PEG20 (pegargiminase) combined with cisplatin and pemetrexed in ASS1‐negative metastatic uveal melanoma
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npj Systems Biology and Applications.2022;[Epub] CrossRef
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Shenglong Li, Xixi Wu, Peng Chen, Yi Pei, Ke Zheng, Wei Wang, Enduo Qiu, Xiaojing Zhang
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Mechanism of HN‑3 cell apoptosis induced by carboplatin: Combination of mitochondrial pathway associated with Ca2+ and the nucleus pathways
Bo Shen, Wenjing Mao, Jin‑Chul Ahn, Phil‑Sang Chung, Peijie He
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Endoplasmic reticulum stress-mediated pathways to both apoptosis and autophagy: Significance for melanoma treatment
Mohamed Hassan
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Modified MVAC as a Second-Line Treatment for Patients with Metastatic Urothelial Carcinoma after Failure of Gemcitabine and Cisplatin Treatment: Jung Hyun Lee, Sung Gu Kang, Seung Tae Kim, Seok Ho Kang, In Keun Choi, Young Je Park, Sang Chul Oh, Deuk Jae Sung, Jae Hong Seo, Jun Cheon, Sang Won Shin, Yeul Hong Kim, Jun Suk Kim, Kyong Hwa Park; Cancer Res Treat. 2014;46(2):172-177. Published online April 15, 2014; DOI: https://doi.org/10.4143/crt.2014.46.2.172

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Purpose

There is no established standard second-line chemotherapy for patients with advanced or metastatic urothelial carcinoma (UC) who failed gemcitabine and cisplatin (GC) chemotherapy. This study was conducted in order to investigate the efficacy and toxicity of modified methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in patients with metastatic UC previously treated with GC.

Materials and Methods

We retrospectively analyzed 28 patients who received modified MVAC between November 2004 and November 2012. All patients failed prior, first-line GC chemotherapy.

Results

The median age of patients was 64.0 years (range, 33.0 to 77.0 years), and 23 (82.1%) patients had an Eastern Cooperative Oncology Group performance status of 0 or 1. The overall response rate and the disease control rate were 36.0% and 64.0%, respectively. After a median follow-up period of 38 weeks (range, 5 to 182 weeks), median progression free survival was 21.0 weeks (95% confidence interval [CI], 6.3 to 35.7 weeks) and median overall survival was 49.0 weeks (95% CI, 18.8 to 79.3 weeks). Grade 3 or 4 hematological toxicities included neutropenia (n=21, 75.0%) and anemia (n=9, 32.1%). Grade 3 or 4 non-hematological toxicities did not occur and there was no treatment-related death.

Conclusion

Modified MVAC appears to be a safe and active chemotherapy regimen in patients with stable physical status and adequate renal function after GC treatment.

Citations

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Second Line Chemotherapy for Advanced and Metastatic Urothelial Carcinoma: Vinflunine and Beyond—A Comprehensive Review of the Current Literature
Christoph Oing, Michael Rink, Karin Oechsle, Christoph Seidel, Gunhild von Amsberg, Carsten Bokemeyer
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Predicting the response of patients with advanced urothelial cancer to methotrexate, vinblastine, Adriamycin, and cisplatin (MVAC) after the failure of gemcitabine and platinum (GP)
Ki Hong Kim, Sung Joon Hong, Kyung Seok Han
BMC Cancer.2015;[Epub] CrossRef

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