The effect of thalidomide on the pharmacokinetics of irinotecan and metabolites in advanced solid tumor patients.

PURPOSE

Irinotecan and thalidomide are commonly administered antineoplastic drugs. Combination treatment may potentiate their antitumor effect and protect against irinotecan's intestinal toxicity. We investigated whether thalidomide can modulate the pharmacokinetics of irinotecan and metabolites.

METHODS

The study employed a crossover design in which advanced solid tumor patients were randomized to two arms and treated with irinotecan 350 mg/m(2) intravenously (IV) every 3 weeks and thalidomide orally (p.o.) 400 mg daily. Pharmacokinetic data when irinotecan was administered as a single agent in each arm were compared to data when the two study agents were co-administered using paired t tests. Eighty percent and 90% confidence intervals for the true difference were also calculated.

RESULTS

The differences in pharmacokinetic parameters and metabolic markers after thalidomide administration were small and unlikely to be clinically significant. With the exception of APC T (1/2), none of the upper confidence limits exceeds a 50% increase.

CONCLUSIONS

This study did not find any clinically meaningful effects of thalidomide on the pharmacokinetics of irinotecan or its metabolites.