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A phase I study of an oral simulated FOLFOX with high dose capecitabine

  • PHASE I STUDIES
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Summary

Background: A phase I study of high-dose capecitabine given over 2 days, along with oxaliplatin, bolus 5FU and leucovorin (LV), was designed to simulate FOLFOX6 without the need for infusional 5FU. Methods: Schedule A included oxaliplatin 100 mg/m2, 5FU 400 mg/m2, and LV 20 mg/m2 (all given IV on days 1 and 15, 28 day cycle). Capecitabine was administered orally every 8 h × 6 doses, days 1 and 15. Schedule B excluded 5FU and LV, maintaining oxaliplatin and capecitabine. Pharmacokinetics were performed for capecitabine for 6 patients on each schedule. Results: 36 patients were treated. The dose-limiting toxicities seen included nausea, dehydration, fatigue, hypotension and confusion. Minimal palmar-plantar erythrodysesthesia was seen. Myelosuppression was common, but not a dose limiting toxicity. The pharmacokinetic parameters for capecitabine were unaltered. Conclusion: Using capecitabine to mimic FOLFOX6 is feasible and well tolerated with a toxicity profile that differs from standard 14-day capecitabine dosing, with less palmar-plantar erythrodysesthesia. The phase II dose for capecitabine in combination with oxaliplatin, 5FU, and LV is 1,500 mg/m2/dose or 2,250 mg/m2/dose in the absence of bolus 5FU/LV.

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Acknowledgements

This study was supported by National Cancer Institute grant UO1CA062491 "Early Clinical Trials of Anti-Cancer Agents with Phase I Emphasis" and National Institutes of Health grant 1ULRR025011 "Clinical and Translational Science Award of the National Center for Reseach Resources". The authors would like to thank the University of Wisconsin Paul P. Carbone Comprehensive Cancer Center (UWCCC) Analytical Instrumentation Laboratory for Pharmacokinetics, Pharmacodynamics, & Pharmacogenetics (3P Lab) for support in the acquisition of the pharmacokinetic data. The authors would like to thank the nurses and research specialist of the UWCCC Phase I Program for their efforts in conducting and managing this trial.

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Authors and Affiliations

  1. University of Wisconsin Paul P Carbone Comprehensive Cancer Center, Madison, WI, USA

    D. Mulkerin, N. K. LoConte, K. D. Holen, D. Alberti, R. Marnocha, J. Kolesar, J. Eickhoff, K. Oliver, C. Feierabend & G. Wilding

  2. The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA

    J. P. Thomas

  3. CHS, UWCCC, 600 Highland Ave, K4/548 Clinical Sciences Center, Madison, WI, 53792, USA

    N. K. LoConte

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  1. D. Mulkerin
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  2. N. K. LoConte
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  3. K. D. Holen
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  4. J. P. Thomas
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  5. D. Alberti
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  6. R. Marnocha
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  7. J. Kolesar
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  8. J. Eickhoff
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  9. K. Oliver
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  10. C. Feierabend
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  11. G. Wilding
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Correspondence to N. K. LoConte.

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Mulkerin, D., LoConte, N.K., Holen, K.D. et al. A phase I study of an oral simulated FOLFOX with high dose capecitabine. Invest New Drugs 27, 461–468 (2009). https://doi.org/10.1007/s10637-008-9210-8

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  • DOI: https://doi.org/10.1007/s10637-008-9210-8

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