Feasibility of biweekly combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in patients with metastatic solid tumors: results of a two-step phase I trial: XELIRI and XELIRINOX.

ABSTRACT

BACKGROUND: Biweekly schedule of capecitabine combined with irinotecan (XELIRI), consecutively with irinotecan and oxaliplatin (XELIRINOX), was evaluated in patients with metastatic cancer from any solid tumors. PATIENTS AND METHODS: In this two-step phase I trial, seventeen and eleven patients were enrolled in the XELIRI and XELIRINOX stages, respectively. RESULTS: In XELIRI, a total of 136 chemotherapy cycles were administered with a median number of 8 cycles per patient (2-16). Main dose-limiting toxicities (DLT) were grade 3-4 neutropenia, with one toxicity-related death. Maximum tolerated dose (MTD) for capecitabine combined with 180 mg/m(2) of irinotecan was 3,500 mg/m(2)/day. In XELIRINOX, capecitabine starting dose was 2,500 mg/m(2)/day. Fifty-eight chemotherapy cycles were administered with a median of 4 cycles per patient (1-16). DLT included 3 grade 4 neutropenia, associated with 1 grade 3 diarrhea, and 1 grade 4 pneumopathy leading to patient death. MTD for capecitabine with 180 mg/m(2) of irinotecan and 85 mg/m(2) of oxaliplatin was 3,000 mg/m(2)/day. The recommended doses for capecitabine were 3,000 and 2,500 mg/m(2)/day D1-D7 in combination with 180 mg/m(2) of irinotecan in XELIRI, plus 85 mg/m(2) of oxaliplatin in XELIRINOX (D1 = D14), respectively. CONCLUSION: XELIRI and XELIRINOX regimens are feasible and warrant further investigation in combination with targeted therapy in metastatic colorectal cancer patients.