Phase I/II trial of capecitabine, oxaliplatin, and irinotecan in combination with bevacizumab in first line treatment of metastatic colorectal cancer

Shouki Bazarbashi, Ali Aljubran, Ahmad Alzahrani, Ahmed Mohieldin, Hussein Soudy, Mohammed Shoukri, Shouki Bazarbashi, Ali Aljubran, Ahmad Alzahrani, Ahmed Mohieldin, Hussein Soudy, Mohammed Shoukri

Abstract

Phase III studies have demonstrated the efficacy of FOLFOXIRI regimens (5-fluorouracil/leucovorin, oxaliplatin, irinotecan) with/without bevacizumab in metastatic colorectal cancer (mCRC). Capecitabine is an orally administered fluoropyrimidine that may be used instead of 5-fluorouracil/leucovorin. We evaluated a triple-chemotherapy regimen of capecitabine, oxaliplatin, and irinotecan, plus bevacizumab in 53 patients with mCRC. A Phase I study identified the maximum tolerated dose of irinotecan as 150 mg/m². Median follow-up in a subsequent Phase II study using this dose was 28 months (74% progressed). For all patients, a complete response was achieved in 4% and a partial response in 60%; median progression-free survival (PFS) was 16 months and median overall survival (OS) was 28 months. Median PFS was longer for patients with an early treatment response (28 vs. 9 months for others; P = 0.024), or early tumor shrinkage (25 vs. 9 months for others; P = 0.006), or for patients suitable for surgical removal of metastases with curative intent (median not reached vs. 9 months for others; P = 0.001). Median OS was longer for patients with early tumor shrinkage (median not reached vs. 22 months for others; P = 0.006) or surgery (median not reached vs. 22 months for others, P = 0.002). K-ras mutations status did not influence PFS (P = 0.88) or OS (P = 0.82). Considerable Grade 3/4 toxicity was encountered (36% for diarrhea, 21% for vomiting and 17% for fatigue). In conclusion, the 3-weekly triple-chemotherapy regimen of capecitabine, oxaliplatin, and irinotecan, plus bevacizumab, was active in the first-line treatment of mCRC, although at the expense of a high level of toxicity.

Trial registration: ClinicalTrials.gov NCT01311050.

Keywords: Bevacizumab; capecitabine; irinotecan; metastatic colorectal cancer; oxaliplatin.

© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Kaplan–Meier estimates of survival in 53 patients.
Figure 2
Figure 2
Kaplan–Meier estimates of progression-free survival and overall survival in subgroups of patients defined according to early tumor shrinkage (in 43 patients), surgical resection (in 53 patients), or K-ras mutation status (in 40 evaluable patients).

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