A Population-Based Clinical Trial of Irinotecan and Carboplatin
Joint Authors
Lau, Derick
Johl, Jewel
Huynh, Minh
Source
Issue
Vol. 2009, Issue 2009 (31 Dec. 2009), pp.1-5, 5 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2009-04-23
Country of Publication
Egypt
No. of Pages
5
Main Subjects
Abstract EN
Purpose.
Phase I trials of anticancer drugs are commonly conducted using the method of modified Fibonacci.
We have developed a population-based design for phase I trials of combining anticancer drugs such as irinotecan and carboplatin.
Patients and Methods.
Intrapatient dose escalation of irinotecan and carboplatin was performed according to a predetermined schema to reach individual dose-limiting toxicity (DLT) in 50 patients with solid tumors refractory to previous chemotherapy.
The individual toxicity-limiting dose levels were analyzed for normal distribution using the method of Ryan-Joiner and subsequently used to determine a population-based maximum tolerated dose (pMTD).
For comparison, a simulation study was performed using the method of modified Fibonacci.
Results.
The most common dose-limiting toxicities (DLTs) included neutropenia (58%), thrombocytopenia (16%), and diarrhea (8%).
The frequency of individual toxicity-limiting dose levels of 50 patients approximated a normal distribution.
The dose levels associated with individual limiting toxicities ranged from level 1 (irinotecan 100 mg/m2 and carboplatin AUC = 4 mg/mL x min) to level 8 (irinotecan 350 mg/m2 and carboplatin AUC = 6).
The pMTD was determined to be dose level 3 (150 mg/m2 for irinotecan and AUC = 5 for carboplatin).
In contrast, the MTD was determined to be dose level 4 (200 mg/m2 for irinotecan and AUC 5 for carboplatin) by modified-Fibonacci simulation.
Conclusions.
The population-based design of phase I trial allows optimization of dose intensity and derivation of a pMTD.
The pMTD has been applied in phase II trial of irinotecan and carboplatin in patients with small-cell lung cancer.
American Psychological Association (APA)
Lau, Derick& Huynh, Minh& Johl, Jewel. 2009. A Population-Based Clinical Trial of Irinotecan and Carboplatin. Journal of Oncology،Vol. 2009, no. 2009, pp.1-5.
https://search.emarefa.net/detail/BIM-473133
Modern Language Association (MLA)
Lau, Derick…[et al.]. A Population-Based Clinical Trial of Irinotecan and Carboplatin. Journal of Oncology No. 2009 (2009), pp.1-5.
https://search.emarefa.net/detail/BIM-473133
American Medical Association (AMA)
Lau, Derick& Huynh, Minh& Johl, Jewel. A Population-Based Clinical Trial of Irinotecan and Carboplatin. Journal of Oncology. 2009. Vol. 2009, no. 2009, pp.1-5.
https://search.emarefa.net/detail/BIM-473133
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-473133