A dose-escalation study of oxaliplatin/capecitabine/irinotecan (XELOXIRI) and bevacizumab as a first-line therapy for patients with metastatic colorectal cancer
- 641 Downloads
The aim of this study was to determine the recommended dose (RD) of a triweekly capecitabine, oxaliplatin, irinotecan, and bevacizumab (XELOXIRI/bevacizumab) regimen that was easier to administer than FOLFOXIRI/bevacizumab, using capecitabine instead of 5-fuorouracil (5-FU), in patients with metastatic colorectal cancer (mCRC).
Patients received oxaliplatin (100 mg/m2, day 1), capecitabine (1,700 mg/m2 per day from day 2 to 15), irinotecan (100, 120, 150 mg/m2 for dose levels 1, 2, 3, day 1), and bevacizumab (7.5 mg/kg, day 1), repeated every 3 weeks. Dose-limiting toxicities (DLTs) were assessed in the first two cycles to determine the maximum tolerated dose (MTD).
Twelve patients received a median of 6.5 cycles of therapy (range 2–12). The DLT was grade 4 neutropenia, observed in one of six patients at dose level 2. The MTD was not reached at dose level 3. Therefore, the RD of irinotecan was defined as 150 mg/m2. The most common grade ≥3 toxicities were neutropenia (41 %), anemia (17 %), diarrhea (8 %), and febrile neutropenia (8 %). The response rate and median progression-free survival were 83 % and 15 months, respectively.
XELOXIRI/bevacizumab is a feasible regimen for patients with mCRC, neutropenia was the DLT, and the RD of irinotecan is 150 mg/m2. The response rate observed is very promising and warrants further investigation.
KeywordsBevacizumab Capecitabine Colorectal cancer Irinotecan Oxaliplatin
Conflict of interest
The authors have no conflict of interest.
- 4.Falcone A, Ricci S, Brunetti I et al (2007) Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol 25:1670–1676CrossRefPubMedGoogle Scholar
- 16.Reinacher-Schick AC, Kubicka S, Freier W et al (2008) Activity of the combination of bevacizumab (Bev) with capecitabine/irinotecan (CapIri/Bev) or capecitabine/oxaliplatin (CapOx/Bev) in advanced colorectal cancer (ACRC): a randomized phase II study of the AIO Colorectal Study Group (AIO trial 0604). J Clin Oncol 26:15s abstract 4030Google Scholar