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. Me...

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Bibliographic Details
Published in:Cancer chemotherapy and pharmacology 2011-12, Vol.68 (6), p.1629-1632
Main Authors: Ramírez, Jacqueline, Wu, Kehua, Janisch, Linda, Karrison, Theodore, House, Larry K., Innocenti, Federico, Cohen, Ezra E. W., Ratain, Mark J.
Format: Article
Language:English
Subjects:
Antineoplastic agents
Antineoplastic Agents, Phytogenic - pharmacokinetics
Biological and medical sciences
Camptothecin - analogs & derivatives
Camptothecin - pharmacokinetics
Cancer Research
Cross-Over Studies
Drug Interactions
Humans
Irinotecan
Medical sciences
Medicine
Medicine & Public Health
Multiple tumors. Solid tumors. Tumors in childhood (general aspects)
Neoplasms - drug therapy
Oncology
Pharmacology. Drug treatments
Pharmacology/Toxicology
Short Communication
Thalidomide - pharmacology
Tumors
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Summary: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.
ISSN:0344-5704
1432-0843
DOI:10.1007/s00280-011-1727-4