Evaristo Maiello1, Gabriele Di Maggio2, Stefano Cordio3, Saverio Cinieri4, Francesco Giuliani5, Salvatore Pisconti6, Antonio Rinaldi7, Antonio Febbraro8, Tiziana Pia Latiano2, Michele Aieta9, Antonio Rossi2, Daniele Rizzi10, Massimo Di Maio11, Giuseppe Colucci10, Roberto Bordonaro3. 1. Division of Medical Oncology, Fondazione IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo (Foggia), Italy. Electronic address: e.maiello@libero.it. 2. Division of Medical Oncology, Fondazione IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo (Foggia), Italy. 3. Medical Oncology Unit, Ospedale Garibaldi, Catania, Italy. 4. Medical Oncology Unit, Antonio Perrino Hospital, Brindisi, Italy. 5. Medical Oncology Unit, National Cancer Institute IRCCS "Giovanni Paolo II", Bari, Italy. 6. Oncology Unit, SG Moscati Hospital, Taranto, Italy. 7. Ospedale Civile, Castellaneta (Taranto), Italy. 8. Oncology Unit, Ospedale Sacro Cuore di Gesù, Fatebenefratelli, Benevento, Italy. 9. Medical Oncology Unit, Department of Onco-Hematology, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture (Potenza), Italy. 10. Gruppo Oncologico Italia Meridionale (GOIM) Trial Office, Bari, Italy. 11. Department of Oncology, University of Turin, Turin, Italy; Medical Oncology Unit, "Ordine Mauriziano" Hospital, Turin, Italy.
Abstract
INTRODUCTION: Biweekly schedule of XELOX-2 (capecitabine plus oxaliplatin) showed interesting results in first-line therapy of patients with metastatic colorectal cancer (mCRC). Bevacizumab plus FOLFOX-4 (oxaliplatin, folinic acid, and infusional5-fluorouracil) is among standard first-line treatment options in this setting. We performed a phase II randomized trial in order to evaluate the activity of bevacizumab plus either FOLFOX-4 or XELOX-2 in first-line therapy of patients with mCRC. MATERIALS AND METHODS:Patients with mCRC were randomized, in a 1:2 ratio, to first-line bevacizumab plus either FOLFOX-4 (Arm A), as calibration arm, or XELOX-2 (Arm B), up to 12 cycles. Patients without progression were further randomized to maintenance bevacizumab alone or with the same induction fluoropyrimidine. The primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival, overall survival, and toxicity. The study design was formally non-comparative, but exploratory comparison was performed. RESULTS: Forty-five patients were randomized in arm A and 87 in arm B with an ORR of 55.6% versus 48.3% (P = .43), respectively. After a median follow-up of 47.2 months, progression-free survival was 10.0 versus 9.9 months (hazard ratio, 0.96; 95% confidence interval, 0.65-1.41; P = .84) and overall survival was 29.8 versus 25.0 months (hazard ratio, 1.21; 95% confidence interval, 0.77-1.92; P = .41), respectively. The main grade 3 to 4 toxicities (% A/B) were: neutropenia 15/3 and nausea 9/5. CONCLUSION: This exploratory analysis showed that biweekly XELOX-2 plus bevacizumab has a comparable ORR with FOLFOX-4 plus bevacizumab in patients with mCRC.
RCT Entities:
INTRODUCTION: Biweekly schedule of XELOX-2 (capecitabine plus oxaliplatin) showed interesting results in first-line therapy of patients with metastatic colorectal cancer (mCRC). Bevacizumab plus FOLFOX-4 (oxaliplatin, folinic acid, and infusional 5-fluorouracil) is among standard first-line treatment options in this setting. We performed a phase II randomized trial in order to evaluate the activity of bevacizumab plus either FOLFOX-4 or XELOX-2 in first-line therapy of patients with mCRC. MATERIALS AND METHODS:Patients with mCRC were randomized, in a 1:2 ratio, to first-line bevacizumab plus either FOLFOX-4 (Arm A), as calibration arm, or XELOX-2 (Arm B), up to 12 cycles. Patients without progression were further randomized to maintenance bevacizumab alone or with the same induction fluoropyrimidine. The primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival, overall survival, and toxicity. The study design was formally non-comparative, but exploratory comparison was performed. RESULTS: Forty-five patients were randomized in arm A and 87 in arm B with an ORR of 55.6% versus 48.3% (P = .43), respectively. After a median follow-up of 47.2 months, progression-free survival was 10.0 versus 9.9 months (hazard ratio, 0.96; 95% confidence interval, 0.65-1.41; P = .84) and overall survival was 29.8 versus 25.0 months (hazard ratio, 1.21; 95% confidence interval, 0.77-1.92; P = .41), respectively. The main grade 3 to 4 toxicities (% A/B) were: neutropenia 15/3 and nausea 9/5. CONCLUSION: This exploratory analysis showed that biweekly XELOX-2 plus bevacizumab has a comparable ORR with FOLFOX-4 plus bevacizumab in patients with mCRC.