Phase II Randomized Trial of Biweekly Bevacizumab, Capecitabine, Oxaliplatin and Irinotecan (BEV- CAPEOXIRI) Versus Triweekly Bevacizumab, Capecitabine and Oxaliplatin (BEV- CAPEOX) in Metastatic Colon Carcinoma

Abstract
Background: Bevacizumab, Capecitabine and Oxaliplatin (BEV-CAPEOX) is an effective combination in patients with Metastatic Colon Carcinoma (MCC). Irinotecan is also an active agent in those patients.
Aim of the Study: To compare toxicity and efficacy of first-line BEV-CAPEOXIRI (consisting of modified biweekly schedule of BEV-CAPEOX plus irinotecan) with BEV-CAPEOX.
Patients and Methods: A total of 65 patients with MCC who are chemo naïve were randomized into 2 groups. Group 1 (n=33) received BEV-CAPEOXIRI and Group 2 (n=32) BEV-CAPEOX.
Results: The incidence of grade 3-4 neutropenia, febrile neutropenia and G3-4 diarrhea were higher in BEV-CAPEOXIRI arm (12% versus 0%, 9% vs. 0% and 18% vs. 3%, respectively) while peripheral neuropathy G1-2 & G3 were higher in BEV-CAPEOX arm (41% & 9% vs. 18% & 3%, respectively) and also higher palmar plantar erythrodys-aesthesia G1-2 (38% vs. 21%). On comparing BEV-CAPEOXIRI with BEV-CAPEOX: Partial remission was observed in 82% vs. 69% of patients, progressive disease in 9% vs. 22% of patients, respectively while 9% of patients in each group had stable disease. Median Progression Free Survival (PFS) was 15 months (95% CI; 14-16) vs. 12 months (95% CI; 11-13), respectively, p=0.01. Median Overall Survival (OS) was 26 months (95% CI; 25-27) vs. 24 months (95% CI; 23, 25), respectively, p=0.02.
Conclusion: In comparison to BEV-CAPEOX, first-line BEV-CAPEOXIRI is more effective with a higher response rate, median PFS/OS, lower neurotoxicity, lower palmar plantar erythrodysaesthesia but higher manageable diarrhea and neutropenia.