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Phase I study of weekly (day 1 and 8) docetaxel in combination with capecitabine in patients with advanced solid malignancies

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Abstract

Purpose

Capecitabine in combination with docetaxel given every 3 weeks has shown a high degree of activity in a number of tumor types, but at the expense of significant toxicity. To improve the therapeutic index, we evaluated a weekly regimen of docetaxel in combination with capecitabine, and determined the maximum tolerated dose, toxicities and pharmacokinetics of this combination.

Patients and methods

Patients with advanced solid malignancies were treated with docetaxel on days 1 and 8, and capecitabine, twice daily on days 1–14, of an every-21-day cycle. Pharmacokinetics of docetaxel were assessed on days 1 and 8 of the first cycle of chemotherapy.

Results

Enrolled in the study were 25 patients. The most frequent toxicities were asthenia, hand-foot syndrome and mucositis. Inability to deliver at least 75% of the planned doses of both drugs during the first two cycles of chemotherapy was noted at dose levels 2, 3 and 4. Dose level 1 (docetaxel 30 mg/m2 and capecitabine 825 mg/m2 twice daily) is the recommended dose for phase II studies. Five patients experienced a partial response, and eight patients had stabilization of disease. Coadministration of capecitabine did not alter the pharmacokinetics of docetaxel.

Conclusion

The regimen consisting of docetaxel 30 mg/m2 (days 1, 8) and capecitabine 825 mg/m2 twice daily (days 1–14) was well tolerated. Capecitabine did not alter pharmacokinetics of docetaxel. Further testing of this regimen in tumor-specific trials, especially gastric, lung and breast cancer, is warranted.

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Acknowledgements

Supported in part by a grant from Aventis Pharmaceuticals, and by grants NCI 2P30 CA47904 and NIH/NCRR/GCRC/#5M01RR00056.

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Authors and Affiliations

  1. Department of Medicine, Division of Hematology–Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Ramesh K. Ramanathan, Sakkaraiappan Ramalingam, Merrill J. Egorin, Chandra P. Belani, Marwan Fakih, Samuel A. Jacobs, David M. Friedland, Dong M. Shin, Gurkamal S. Chatta & William C. Zamboni

  2. Molecular Therapeutics/Drug Discovery Program, University of Pittsburgh Cancer Institute, UPMC Cancer Pavilion, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA

    Ramesh K. Ramanathan, Sakkaraiappan Ramalingam, Merrill J. Egorin, Chandra P. Belani, Douglas M. Potter, Laura L. Jung, Sandra Strychor, Samuel A. Jacobs, Dong M. Shin, Gurkamal S. Chatta, Susan Tutchko & William C. Zamboni

  3. Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

    Douglas M. Potter

  4. Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA

    William C. Zamboni

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  1. Ramesh K. Ramanathan
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  2. Sakkaraiappan Ramalingam
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  3. Merrill J. Egorin
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  4. Chandra P. Belani
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  5. Douglas M. Potter
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  6. Marwan Fakih
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  7. Laura L. Jung
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  8. Sandra Strychor
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  9. Samuel A. Jacobs
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  10. David M. Friedland
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  11. Dong M. Shin
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  12. Gurkamal S. Chatta
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  13. Susan Tutchko
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  14. William C. Zamboni
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Corresponding author

Correspondence to Ramesh K. Ramanathan.

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Ramanathan, R.K., Ramalingam, S., Egorin, M.J. et al. Phase I study of weekly (day 1 and 8) docetaxel in combination with capecitabine in patients with advanced solid malignancies. Cancer Chemother Pharmacol 55, 354–360 (2005). https://doi.org/10.1007/s00280-004-0909-8

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  • DOI: https://doi.org/10.1007/s00280-004-0909-8

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