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

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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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Acknowledgments

We thank the patients who participated in this trial.

Author information

Authors and Affiliations

  1. Developmental Therapeutics Program, Case Comprehensive Cancer Center, Cleveland, OH, USA

    Smitha S. Krishnamurthi, Joanna M. Brell, Charles L. Hoppel, Karen C. Weaver, Xiaolin Li, Stephen T. Ingalls, Afshin Dowlati, Matthew M. Cooney, Joseph Gibbons, Beth A. Overmoyer & Scot C. Remick

  2. Department of Medicine, University Hospitals Case Medical Center, Cleveland, OH, USA

    Smitha S. Krishnamurthi, Joanna M. Brell, Charles L. Hoppel, Afshin Dowlati, Matthew M. Cooney, Joseph Gibbons, Beth A. Overmoyer & Scot C. Remick

  3. Department of Pharmacology, University Hospitals Case Medical Center, Cleveland, OH, USA

    Charles L. Hoppel, Xiaolin Li & Stephen T. Ingalls

  4. University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA

    Merrill J. Egorin & Eleanor G. Zuhowski

  5. Division of Biostatistics, Case Comprehensive Cancer Center, Cleveland, OH, USA

    Mark D. Schluchter

  6. National Cancer Institute, Investigational Drug Branch, Cancer Therapy Evaluation Program, Bethesda, MD, USA

    S. Percy Ivy

  7. University Hospitals Case Medical Center, 11100 Euclid Ave. Lakeside 1243, Cleveland, OH, 44106, USA

    Smitha S. Krishnamurthi

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  1. Smitha S. Krishnamurthi
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  2. Joanna M. Brell
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Corresponding author

Correspondence to Smitha S. Krishnamurthi.

Additional information

Supported in part by NIH grants U01 CA62502, M01-RR-00080, K12 CA76917 (SSK), P30 CA43703, U01-CA099168-01 and P30CA47904. Published in part in: Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 22, No 14S (July 15 Supplement), 2004: 2111.

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Krishnamurthi, S.S., Brell, J.M., Hoppel, C.L. et al. Phase I clinical and pharmacokinetic study of oxaliplatin, irinotecan and capecitabine. Cancer Chemother Pharmacol 63, 441–450 (2009). https://doi.org/10.1007/s00280-008-0754-2

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