Efficacy of oxaliplatin plus capecitabine or infusional fluorouracil/leucovorin in patients with metastatic colorectal cancer: A pooled analysis of randomized trials

Hendrik Tobias Arkenau, Dirk Arnold, Jim Cassidy, Eduardo Diaz-Rubio, Jean Yves Douillard, Howard Hochster, Andrea Martoni, Axel F Grothey, Axel Hinke, Wolff Schmiegel, Hans Joachim Schmoll, Rainer Porschen

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Abstract

Purpose: 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. Patients and Methods: 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. Results: 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)5910-5917
Number of pages8
JournalJournal of Clinical Oncology
Volume26
Issue number36
DOIs
StatePublished - Dec 20 2008

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oxaliplatin
Leucovorin
Fluorouracil
Colorectal Neoplasms
Hand-Foot Syndrome
Odds Ratio
Survival
Capecitabine
Neutropenia
Thrombocytopenia
Meta-Analysis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Efficacy of oxaliplatin plus capecitabine or infusional fluorouracil/leucovorin in patients with metastatic colorectal cancer : A pooled analysis of randomized trials. / Arkenau, Hendrik Tobias; Arnold, Dirk; Cassidy, Jim; Diaz-Rubio, Eduardo; Douillard, Jean Yves; Hochster, Howard; Martoni, Andrea; Grothey, Axel F; Hinke, Axel; Schmiegel, Wolff; Schmoll, Hans Joachim; Porschen, Rainer.

In: Journal of Clinical Oncology, Vol. 26, No. 36, 20.12.2008, p. 5910-5917.

Research output: Contribution to journalArticle

Arkenau, HT, Arnold, D, Cassidy, J, Diaz-Rubio, E, Douillard, JY, Hochster, H, Martoni, A, Grothey, AF, Hinke, A, Schmiegel, W, Schmoll, HJ & Porschen, R 2008, 'Efficacy of oxaliplatin plus capecitabine or infusional fluorouracil/leucovorin in patients with metastatic colorectal cancer: A pooled analysis of randomized trials', Journal of Clinical Oncology, vol. 26, no. 36, pp. 5910-5917. https://doi.org/10.1200/JCO.2008.16.7759
Arkenau, Hendrik Tobias ; Arnold, Dirk ; Cassidy, Jim ; Diaz-Rubio, Eduardo ; Douillard, Jean Yves ; Hochster, Howard ; Martoni, Andrea ; Grothey, Axel F ; Hinke, Axel ; Schmiegel, Wolff ; Schmoll, Hans Joachim ; Porschen, Rainer. / Efficacy of oxaliplatin plus capecitabine or infusional fluorouracil/leucovorin in patients with metastatic colorectal cancer : A pooled analysis of randomized trials. In: Journal of Clinical Oncology. 2008 ; Vol. 26, No. 36. pp. 5910-5917.
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abstract = "Purpose: 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. Patients and Methods: 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. Results: 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. Conclusion: 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.",
author = "Arkenau, {Hendrik Tobias} and Dirk Arnold and Jim Cassidy and Eduardo Diaz-Rubio and Douillard, {Jean Yves} and Howard Hochster and Andrea Martoni and Grothey, {Axel F} and Axel Hinke and Wolff Schmiegel and Schmoll, {Hans Joachim} and Rainer Porschen",
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T1 - Efficacy of oxaliplatin plus capecitabine or infusional fluorouracil/leucovorin in patients with metastatic colorectal cancer

T2 - A pooled analysis of randomized trials

AU - Arkenau, Hendrik Tobias

AU - Arnold, Dirk

AU - Cassidy, Jim

AU - Diaz-Rubio, Eduardo

AU - Douillard, Jean Yves

AU - Hochster, Howard

AU - Martoni, Andrea

AU - Grothey, Axel F

AU - Hinke, Axel

AU - Schmiegel, Wolff

AU - Schmoll, Hans Joachim

AU - Porschen, Rainer

PY - 2008/12/20

Y1 - 2008/12/20

N2 - Purpose: 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. Patients and Methods: 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. Results: 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. Conclusion: 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.

AB - Purpose: 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. Patients and Methods: 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. Results: 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. Conclusion: 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.

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