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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 3/2009

01-02-2009 | Original Article

Phase I clinical and pharmacokinetic study of oxaliplatin, irinotecan and capecitabine

Authors: Smitha S. Krishnamurthi, Joanna M. Brell, Charles L. Hoppel, Merrill J. Egorin, Karen C. Weaver, Xiaolin Li, Stephen T. Ingalls, Eleanor G. Zuhowski, Mark D. Schluchter, Afshin Dowlati, Matthew M. Cooney, Joseph Gibbons, Beth A. Overmoyer, S. Percy Ivy, Scot C. Remick

Published in: Cancer Chemotherapy and Pharmacology | Issue 3/2009

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Abstract

Purpose

To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of the combination of weekly oxaliplatin × 4, weekly irinotecan × 4 and capecitabine Monday through Friday for 4 weeks of every 6 week cycle in patients with solid tumors; to determine the pharmacokinetic profile of these agents in this combination; to observe patients for clinical anti-tumor response.

Methods

Twenty-two patients with metastatic solid tumors received oxaliplatin 60 mg/m2 weekly × 4, irinotecan beginning at a dose of 40 mg/m2 weekly × 4, and capecitabine Monday through Friday for 4 weeks of every 6 week cycle, initially at 1,000 mg twice daily (bid).

Results

The MTD was oxaliplatin 60 mg/m2 weekly × 4, irinotecan 50 mg/m2 weekly × 4 and capecitabine 450 mg bid Monday through Friday for 4 weeks of every 6 week cycle. One of six patients at this dose level developed DLT of nausea, vomiting, and diarrhea. Among patients treated with a constant capecitabine dose of 450 mg bid, there was a higher mean AUC of 5-FU in women than in men (mean ± SD: 892 ± 287 nM h vs. 537 ± 182 nM h; Mann–Whitney two-tailed, P = 0.02). There was one complete response in a patient with gastric cancer.

Conclusion

The novel schedule of weekly oxaliplatin, weekly irinotecan, and capecitabine Monday through Friday, all administered for 4 weeks of every 6 week cycle, evaluated in this phase I trial is well-tolerated and demonstrated activity in a patient with gastric cancer.
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Metadata
Title
Phase I clinical and pharmacokinetic study of oxaliplatin, irinotecan and capecitabine
Authors
Smitha S. Krishnamurthi
Joanna M. Brell
Charles L. Hoppel
Merrill J. Egorin
Karen C. Weaver
Xiaolin Li
Stephen T. Ingalls
Eleanor G. Zuhowski
Mark D. Schluchter
Afshin Dowlati
Matthew M. Cooney
Joseph Gibbons
Beth A. Overmoyer
S. Percy Ivy
Scot C. Remick
Publication date
01-02-2009
Publisher
Springer-Verlag
Published in
Cancer Chemotherapy and Pharmacology / Issue 3/2009
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-008-0754-2

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