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.
RCT Entities:
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 tumorpatients 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.
Authors: Miguel Villalona-Calero; Larry Schaaf; Gary Phillips; Gregory Otterson; Kevin Panico; Wenrui Duan; Barbara Kleiber; Manisha Shah; Donn Young; Wan-Hong Wu; John Kuhn Journal: Cancer Chemother Pharmacol Date: 2006-05-10 Impact factor: 3.333
Authors: L Iyer; S Das; L Janisch; M Wen; J Ramírez; T Karrison; G F Fleming; E E Vokes; R L Schilsky; M J Ratain Journal: Pharmacogenomics J Date: 2002 Impact factor: 3.550
Authors: Camilo E Fadul; Linda S Kingman; Louise P Meyer; Bernard F Cole; Clifford J Eskey; C Harker Rhodes; David W Roberts; Herbert B Newton; J Marc Pipas Journal: J Neurooncol Date: 2008-07-26 Impact factor: 4.130
Authors: Femke M de Man; Andrew K L Goey; Ron H N van Schaik; Ron H J Mathijssen; Sander Bins Journal: Clin Pharmacokinet Date: 2018-10 Impact factor: 6.447