TY - JOUR
T1 - Phase II trial of 5-fluorouracil/leucovorin/gemcitabine/cisplatin as second-line treatment in patients with metastatic or recurrent colorectal carcinoma
T2 - A cancer therapeutics research group study
AU - Chang, Alex Y.
AU - Lopes, Gilberto
AU - Koo, Wen Hsin
AU - Lim, Robert
AU - Foo, Kian Fong
AU - Wong, John
N1 - Funding Information:
This study was supported by Eli Lilly and Co. Other participants of this study are listed below. Johns Hopkins Singapore International Medical Center, Singapore: Wen Son Hsieh, MD; National University Hospital, Singapore: Lim Hong Liang, MD, Goh Boon Cher, MD, Alvin Wong, MD, Pornchai Jonglertham, MD, Lim Siew Eng, MD, Yong Wei Peng, MD, Wong Seng Weng, MD, Ross Soo, MD, Lee Soo Chin, MD, Benjamin Mow, MD; National Cancer Center, Singapore: Wong Zee Wan, MD, Tay Miah Hiang, MD, Simon Ong, MD.
PY - 2007/9
Y1 - 2007/9
N2 - Background: Second-line treatment of relapsed or metastatic colorectal cancer (CRC) after failure of treatment with a fluoropyrimidine is composed of oxaliplatin in combination with a fluoropyrimidine or an irinotecan-containing regimen. Cisplatin and gemcitabine are synergistic in preclinical studies, as is 5-fluorouracil (5-FU) combined with either agent. Fixed-rate infusional gemcitabine is more effective than bolus administration in animal models. Patients and Methods: A 2-stage phase II trial was conducted to assess the efficacy (the primary endpoint was response rate) and safety of a regimen consisting of 5-FU 400 mg/m2 as an intravenous bolus at the middle of a 60-minute infusion of leucovorin 100 mg/m2, followed by gemcitabine 800 mg/m2 over 80 minutes, and cisplatin 20 mg/m 2 over 15 minutes. Treatment was repeated weekly for 3 weeks followed by a 1-week rest. Patients with advanced CRC were eligible if they had experienced treatment failure with fluoropyrimidine-based therapy. Results: Nineteen patients were enrolled. The median age was 60 years; 15 patients were men and 4 were women. Twelve patients had colon cancer and 7 had rectal cancer. Sites of metastasis were as follows: liver (n = 10), lung (n = 8), skin (n = 1), and non-regional lymph nodes (n = 1). All patients had an Eastern Cooperative Oncology Group performance status of 0/1. A total of 44 cycles of chemotherapy were delivered (median, 2 cycles; range, 1-5 cycles). One patient exhibited a partial response (5%), 8 had stable disease (42%), and 5 experienced disease progression (26%); another 5 patients were nonevaluable (26%). The median time to progression was 8 weeks and median survival was 36 weeks. Grade 3/4 toxicities were as follows: diarrhea (n = 1), dyspnea (n = 1), pneumonia (n = 1), neutropenia (n = 2), and thrombocytopenia (n = 1). Conclusion: Despite acceptable toxicity and a reasonable overall survival, the combination of 5-FU/leucovorin/gemcitabine/cisplatin does not seem to improve current standard therapy in the second-line treatment of patients with CRC in whom a first-line fluoropyrimidine-containing regimen has failed.
AB - Background: Second-line treatment of relapsed or metastatic colorectal cancer (CRC) after failure of treatment with a fluoropyrimidine is composed of oxaliplatin in combination with a fluoropyrimidine or an irinotecan-containing regimen. Cisplatin and gemcitabine are synergistic in preclinical studies, as is 5-fluorouracil (5-FU) combined with either agent. Fixed-rate infusional gemcitabine is more effective than bolus administration in animal models. Patients and Methods: A 2-stage phase II trial was conducted to assess the efficacy (the primary endpoint was response rate) and safety of a regimen consisting of 5-FU 400 mg/m2 as an intravenous bolus at the middle of a 60-minute infusion of leucovorin 100 mg/m2, followed by gemcitabine 800 mg/m2 over 80 minutes, and cisplatin 20 mg/m 2 over 15 minutes. Treatment was repeated weekly for 3 weeks followed by a 1-week rest. Patients with advanced CRC were eligible if they had experienced treatment failure with fluoropyrimidine-based therapy. Results: Nineteen patients were enrolled. The median age was 60 years; 15 patients were men and 4 were women. Twelve patients had colon cancer and 7 had rectal cancer. Sites of metastasis were as follows: liver (n = 10), lung (n = 8), skin (n = 1), and non-regional lymph nodes (n = 1). All patients had an Eastern Cooperative Oncology Group performance status of 0/1. A total of 44 cycles of chemotherapy were delivered (median, 2 cycles; range, 1-5 cycles). One patient exhibited a partial response (5%), 8 had stable disease (42%), and 5 experienced disease progression (26%); another 5 patients were nonevaluable (26%). The median time to progression was 8 weeks and median survival was 36 weeks. Grade 3/4 toxicities were as follows: diarrhea (n = 1), dyspnea (n = 1), pneumonia (n = 1), neutropenia (n = 2), and thrombocytopenia (n = 1). Conclusion: Despite acceptable toxicity and a reasonable overall survival, the combination of 5-FU/leucovorin/gemcitabine/cisplatin does not seem to improve current standard therapy in the second-line treatment of patients with CRC in whom a first-line fluoropyrimidine-containing regimen has failed.
KW - Chemotherapy
KW - Fluoropyrimidines
KW - Survival
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U2 - 10.3816/CCC.2007.n.033
DO - 10.3816/CCC.2007.n.033
M3 - Article
AN - SCOPUS:35348903408
VL - 6
SP - 646
EP - 651
JO - Clinical Colorectal Cancer
JF - Clinical Colorectal Cancer
SN - 1533-0028
IS - 9
ER -
