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

Goff LW, Benson AB, LoRusso PM, Tan AR, Berlin JD, Denis LJ, Benner RJ, Yin D, Rothenberg ML
Invest New Drugs. 2012 30 (1): 290-8

PMID: 20857171 · DOI:10.1007/s10637-010-9528-x

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.

MeSH Terms (18)

Administration, Oral Adult Aged Aged, 80 and over Antineoplastic Combined Chemotherapy Protocols Camptothecin Capecitabine Deoxycytidine Drug Administration Schedule Female Fluorouracil Humans Irinotecan Male Maximum Tolerated Dose Middle Aged Neoplasms Treatment Outcome

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