• Otto Soepenberg, Herlinde Dumez, Jaap Verweij, Floris A de Jong, Maja J A de Jonge, José Thomas, EskensFerry A L MFA, Ron H N van Schaik, Johan Selleslach, Judith Ter Steeg, Patricia Lefebvre, Sylvie Assadourian, Ger-Jan Sanderink, Alex Sparreboom, and Allan T van Oosterom.
• Daniel den Hoed Cancer Center, Department of Medical Oncology, Erasmus University Medical Center Rotterdam, Groene Hilledijk 301, 3075 EA Rotterdam, the Netherlands. o.soepenberg@erasmusmc.nl
• Clin Cancer Res. 2005 Feb 15; 11 (4): 1504-11.

PurposeTo characterize the maximum-tolerated dose, recommended dose, dose-limiting toxicities (DLT), pharmacokinetic profile, and food effect of orally administered irinotecan formulated as new semisolid matrix capsules.Experimental DesignIrinotecan was given orally in fasted patients once daily for 5 consecutive days and repeated every 3 weeks. Patients were randomly assigned to take the drug along with a high-fat, high-calorie breakfast for the administration at day 1 of the first or second cycle. Dosages tested were 70 and 80 mg/m(2)/day.ResultsTwenty-five patients received 101 cycles of therapy (median two cycles, range 1-15). During the first cycle, grade 3 delayed diarrhea and grade 3 fever were the DLTs at the dosage of 80 mg/m(2)/day in three out of five patients. Hematologic and nonhematologic toxicities were mild to moderate. Exposure to the active metabolite SN-38 was relatively high compared with i.v. infusion, but no relevant accumulation was observed. Food had no significant effect on irinotecan pharmacokinetics. One confirmed partial remission and 10 disease stabilizations were observed in previously treated patients. No association was found between the UGT1A1*28 genotype and the risk of severe irinotecan-induced toxicity.ConclusionsFor oral irinotecan, a dose of 70 mg/m(2)/day for 5 consecutive days every 3 weeks is recommended for further studies. Delayed diarrhea was the main DLT, similar to that observed with intravenously administered irinotecan. This study confirms that oral administration of irinotecan is feasible and may have favorable pharmacokinetic characteristics.

57 keywords...

hide…