Efficacy of Oxaliplatin Plus Capecitabine or Infusional Fluorouracil/Leucovorin in Patients With Metastatic Colorectal Cancer: A Pooled Analysis of Randomized Trials

• Published in: Journal of clinical oncology Vol. 26; no. 36; pp. 5910 - 5917
• Main Authors: ARKENAU, Hendrik-Tobias, ARNOLD, Dirk, SCHMOLL, Hans-Joachim, PORSCHEN, Rainer, CASSIDY, Jim, DIAZ-RUBIO, Eduardo, DOUILLARD, Jean-Yves, HOCHSTER, Howard, MARTONI, Andrea, GROTHEY, Axel, HINKE, Axel, SCHMIEGEL, Wolff
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 20.12.2008
• Subjects: Antimetabolites, Antineoplastic - administration & dosage; Antineoplastic Agents - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - toxicity; Biological and medical sciences; Capecitabine; Colorectal Neoplasms - drug therapy; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Fluorouracil - administration & dosage; Fluorouracil - analogs & derivatives; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Infusions, Intravenous; Leucovorin - administration & dosage; Medical sciences; Neutropenia - chemically induced; Organoplatinum Compounds - administration & dosage; Randomized Controlled Trials as Topic; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Survival Rate; Thrombocytopenia - chemically induced; Tumors; Vitamin B Complex - administration & dosage; Antineoplastic agent; Rectal disease; Capecitabine; Colorectal cancer; Calcium folinate; Metastasis; Randomization; Cancerology; Oxaliplatin; Intestinal disease; Clinical trial; Advanced stage; Pyrimidine nucleoside; Platinum II Complexes; Fluorouracil; Human; Enzyme; Fluoropyrimidine derivatives; Transferases; Treatment efficiency; Enzyme inhibitor; Malignant tumor; Prodrug; Thymidylate synthase; Colonic disease; Alkylating agent; Antimetabolic; Methyltransferases; Pyrimidine derivatives; Digestive diseases; Cancer
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2008.16.7759

Six randomized phase II and III trials have investigated the role of oxaliplatin (OX) in combination with capecitabine (CAP) or infusional fluorouracil (FU) in metastatic colorectal cancer. This meta-analysis compared the efficacy of CAP/OX compared with infusional FU/OX. This analysis compared all published CAP/OX versus infusional FU/OX regimens. A total of 3,494 patients (FU, n = 1,737; CAP, n = 1,757) were analyzed for response rate (RR), progression-free (PFS), overall survival (OS), and toxicity. The fixed-effect pooled estimate for RR showed higher RR for FU-based regimens (Odds ratio [OR] = 0.85; 95% CI, 0.74 to 0.97; P = .02) whereas the analysis of chemotherapy-only trials, excluding the bevacizumab containing NO16966 and TREE 2 trials, led to an OR of 0.74 (95% CI, 0.60 to 0.92; P = .007). However, for PFS (hazard ratio [HR] = 1.04; 95% CI, 0.96 to 1.12; P = .17) and OS (HR = 1.04; 95% CI, 0.95 to 1.12; P = .41) all models suggested similar outcome within the range of noninferiority. Grade 3/4 toxicities (thrombocytopenia-HR = 2.07, 95% CI, 1.42 to 3.03; P < .0002; diarrhea-HR = 1.34; 95% CI, 1.08 to 1.66; P < .0009; and grade 2/3 hand-foot-syndrome [HFS]-HR = 3.54; 95% CI, 2.07 to 6.05; P < .00001) were less prominent with FU-based regimens whereas neutropenia (HR = 0.15; 95% CI, 0.11 to 0.19; P < .00001) was lower in the CAP regimens. The combination of CAP and OX resulted in lower RR, but this did not affect PFS and OS, which were similar in both treatment arms. The toxicity analysis showed the characteristic toxicity of each of the different FU schedules, with thrombocytopenia and HFS consistently more prominent in the CAP regimens.