Capecitabine is an oral fluoropyrimidine prodrug, which is converted to fluorouracil (5-FU) predominantly in the tumor cells. We conducted a phase I/II study to assess the safety and efficacy of capecitabine plus Irinotecan (CPT) (XELIRI) plus BV in Japanese patients with metastatic colorectal cancer (mCRC). The results of phase I part were reported at the previous meeting, and then planned interim analysis of phase II was carried out.Methods
Patients with prior chemotherapy including oxaliplatin and BV for mCRC, wild or hetero type of UGT1A1*6*28 were eligible for this study. This was a phase I study composed of two steps, and dose-limiting toxicity (DLT) was assessed during the first treatment cycle. Treatment comprised capecitabine 1000 mg/m2 twice daily from the evening of day 1 to the morning of day 8, intravenous CPT 180 mg/m2 on day 1, and BV 5mg/kg on day 1 every 2 weeks. To evaluate the initial safety, 3–6 patients received XELIRI + BV (CPT 150 mg/m2) in step 1, and 6 patients received XELIRI + BV (CPT 180 mg/m2) in step 2. If DLT occurred in one patient in step 1, three patients would be newly added to step 1, and if in none of 3 or 1–2 of six patients, the step 2 would be started. If DLT occurred in less than or equal to two of six patients in step 2, phase II study would be proceeded, and if In more than two of six patients, phase II would be conducted at the recommended dose of step 1. Interim analysis of toxicity was planed at the end of second cycle in tenth patient in Phase II.Results
In phase I, initial safety of nine patients was confirmed without occurrence of DLT. Recommended dose of CPT was determined as 180 mg/m2. Adverse events observed in interim analysis of early toxicity in phase II were: neutropenia in 6; nausea in 4; diarrhea in 6; alopecia in 5; albumin decreased in 6. One patient required a dose reduction due to grade 3 nausea and grade 3 fatigue during the initial cycle of therapy. Another patient discontinued treatment due to intestinal pneumonia considered as CPT-related.Conclusions
In mCRC patients with wild or hetero of UGT1A1*6*28 genotype, safety of biweekly XELIRI + BV was confirmed and recommended dose of CPT-11 was determined as 180 mg/m2. According to the interim analysis of safety of phase II study, safety in early cycle was demonstrated. Phase II study is now on-going.