Phase I study of oral irinotecan as a single-agent and given sequentially with capecitabine.

Purpose: To assess the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of orally administered irinotecan in the semi-solid matrix (SSM) formulation, both as a single agent and in sequential combination with capecitabine, in patients with advanced solid tumors.

Patients And Methods: Forty-three patients were treated with irinotecan given as a single oral daily dose on days 1-5 every three weeks. An additional forty patients were treated with sequential oral irinotecan given daily on days 1-5 followed by capecitabine given orally as a divided dose twice daily on days 6-14 of each three week cycle.

Results: The MTD of single-agent oral irinotecan was estimated to be 60 mg/m(2)/day, and DLT included diarrhea, nausea, and neutropenia. In an initial group of patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2, the MTD of sequential oral irinotecan/capecitabine was estimated to be 40/1600 mg/m(2)/day with DLT of delayed diarrhea. In a subsequent group of patients with ECOG PS of 0 or 1, the MTD for the sequential combination was 50/2000 mg/m(2)/day. The most common adverse events were fatigue, diarrhea, nausea/vomiting and dehydration. Pharmacokinetic (PK) evaluation showed that oral irinotecan was rapidly absorbed and effectively converted to the active metabolite, SN-38, achieving approximately 50% of the SN-38 systemic exposure resulting from an equivalent IV dose.

Conclusions: Oral irinotecan can be safely administered as a single agent or in sequential combination with capecitabine. The efficacy of oral irinotecan should be explored further as a potentially convenient alternative to IV chemotherapy.