Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 6/2011

01-12-2011 | Short Communication

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

Authors: Jacqueline Ramírez, Kehua Wu, Linda Janisch, Theodore Karrison, Larry K. House, Federico Innocenti, Ezra E. W. Cohen, Mark J. Ratain

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2011

Login to get access

Abstract

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/m2 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.
Literature
1.
Gupta E, Lestingi TM, Mick R, Ramirez J, Vokes EE, Ratain MJ (1994) Metabolic fate of irinotecan in humans: correlation of glucuronidation with diarrhea. Cancer Res 54:3723–3725PubMed
2.
Govindarajan R (2000) Irinotecan and thalidomide in metastatic colorectal cancer. Oncology (Williston Park) 14:29–32
3.
Govindarajan R, Heaton KM, Broadwater R, Zeitlin A, Lang NP, Hauer-Jensen M (2000) Effect of thalidomide on gastrointestinal toxic effects of irinotecan. Lancet 356:566–567PubMedCrossRef
4.
Govindarajan R (2002) Irinotecan/thalidomide in metastatic colorectal cancer. Oncology (Williston Park) 16:23–26
5.
Miller AA, Case D, Atkins JN, Giguere JK, Bearden JD (2006) Phase II study of carboplatin, irinotecan, and thalidomide in patients with advanced non-small cell lung cancer. J Thorac Oncol 1:832–836PubMedCrossRef
6.
Yang X, Hu Z, Chan SY, Goh BC, Duan W, Chan E, Zhou S (2005) Simultaneous determination of the lactone and carboxylate forms of irinotecan (CPT-11) and its active metabolite SN-38 by high-performance liquid chromatography: application to plasma pharmacokinetic studies in the rat. J Chromatogr B Analyt Technol Biomed Life Sci 821:221–228PubMedCrossRef
7.
Yang XX, Hu ZP, Chan SY, Duan W, Ho PC, Boelsterli UA, Ng KY, Chan E, Bian JS, Chen YZ, Huang M, Zhou SF (2006) Pharmacokinetic mechanisms for reduced toxicity of irinotecan by coadministered thalidomide. Curr Drug Metab 7:431–455PubMedCrossRef
8.
Fadul CD, Kingman LS, Meyer LP, Cole BF, Eskey CJ, Rhodes CH, Roberts DW, Newton HB, Pipas JM (2008) A phase II study of thalidomide and irinotecan for treatment of glioblastoma multiforme. J Neurooncol 90:229–235PubMedCrossRef
9.
Yang XX, Hu ZP, Xu AL, Duan W, Zhu YZ, Huang M, Sheu FS, Zhang Q, Bian JS, Chan E, Li X, Wang JC, Zhou SF (2006) A mechanistic study on reduced toxicity of irinotecan by coadministered thalidomide, a tumor necrosis factor-alpha inhibitor. J Pharmacol Exp Ther 319:82–104PubMedCrossRef
10.
Iyer L, Das S, Janisch L, Wen M, Ramirez J, Karrison T, Fleming GF, Vokes EE, Schilsky RL, Ratain MJ (2002) UGT1A1*28 polymorphism as a determinant of irinotecan disposition and toxicity. Pharmacogenomics J 2:43–47PubMedCrossRef
11.
Villalona-Calero M, Schaaf L, Phillips G, Otterson G, Panico K, Duan W, Kleiber B, Shah M, Young D, Wu WH, Kuhn J (2007) Thalidomide and celecoxib as potential modulators of irinotecan’s activity in cancer patients. Cancer Chemother Pharmacol 59:23–33PubMedCrossRef
12.
Ramírez J, Komoroski BJ, Mirkov S, Graber AY, Fackenthal DL, Schuetz EG, Das S, Ratain MJ, Innocenti F, Strom SC (2006) Study of the genetic determinants of UGT1A1 inducibility by phenobarbital in cultured human hepatocytes. Pharmacogenet Genomics 16:79–86PubMedCrossRef
13.
Murry DJ, Cherrick I, Salama V, Berg S, Bernstein M, Kuttesch N, Blaney SM (2002) Influence of phenytoin on the disposition of irinotecan: a case report. J Pediatr Hematol Oncol 24:130–133PubMedCrossRef
14.
Allegrini G, Di Paolo A, Cerri E, Cupini S, Amatori F, Masi G, Danesi R, Marcucci L, Bocci G, Del Tacca M, Falcone A (2006) Irinotecan in combination with thalidomide in patients with advanced solid tumors: a clinical study with pharmacodynamic and pharmacokinetic evaluation. Cancer Chemother Pharmacol 58:585–596PubMedCrossRef
Metadata
Title
The effect of thalidomide on the pharmacokinetics of irinotecan and metabolites in advanced solid tumor patients
Authors
Jacqueline Ramírez
Kehua Wu
Linda Janisch
Theodore Karrison
Larry K. House
Federico Innocenti
Ezra E. W. Cohen
Mark J. Ratain
Publication date
01-12-2011
Publisher
Springer-Verlag
Published in
Cancer Chemotherapy and Pharmacology / Issue 6/2011
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-011-1727-4

Other articles of this Issue 6/2011

Cancer Chemotherapy and Pharmacology 6/2011 Go to the issue

Original Article

Pharmacokinetic evaluation of the vinorelbine–lapatinib combination in the treatment of breast cancer patients

Original Article

Tumor growth modeling from clinical trials reveals synergistic anticancer effect of the capecitabine and docetaxel combination in metastatic breast cancer

Original Article

Quercetin enhances 5-fluorouracil-induced apoptosis in MSI colorectal cancer cells through p53 modulation

Mini Review

Translational research of a novel humanized epidermal growth factor receptor-related protein: a putative inhibitor of pan-ErbB

Original Article

Erufosine, an alkylphosphocholine, with differential toxicity to human cancer cells and bone marrow cells

Original Article

Lack of food effect on single-dose pharmacokinetics of brivanib, and safety and efficacy following multiple doses in subjects with advanced or metastatic solid tumors
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits