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Five-day infusion of fluorodeoxyuridine with high-dose oral leucovorin: a phase I study

  • Original Articles
  • Oral Leucovorin, Fluorodeoxyrudine, Infusion
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Summary

Fluorodeoxyuridine (FUdR) interferes with cellular metabolism by inhibiting thymidylate synthase. Therefore, we sought to modulate its activity with leucovorin (LV) and to identify the maximally tolerated dose given as a 5-day continuous intravenous infusion in combination with oral administration of LV at a dose of 100 mg every hour for four doses immediately preceding the start of the FUdR infusion and then every 4 h for the entire duration of FUdR treatment. Patients were evaluated at six FUdR dose levels ranging from 0.1 to 0.375 mg/kg per day. Severe or life-threatening mucositis was first observed in two of six patients treated at 0.25 mg/kg daily. Further escalation of the dose to 0.3 mg/kg per day resulted in grade 2 mucositis in four of six patients and in grade 3 mucositis in two cases. A dose of 0.375 mg/kg daily resulted in grade 3 toxicity in all three patients treated. Other types of toxicities included skin rash and hand-foot syndrome, but no hematologic toxicities were observed. Stable disease was observed in 11 of 24 evaluable patients, including 3 subjects with renal cell carcinoma. Our recommended dose for phase II trials is 0.3 mg/kg FUdR per day.

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Authors and Affiliations

  1. Department of Radiation and Cellular Oncology, The University of Chicago Pritzker School of Medicine, 60637, Chicago, IL, USA

    Everett E. Vokes, Nicholas J. Vogelzang, Elizabeth E. Warfield, Mark J. Ratain & Richard L. Schilsky

  2. Committee on Clinical Pharmacology, The University of Chicago Pritzker School of Medicine, 60637, Chicago, IL, USA

    Everett E. Vokes, Nicholas J. Vogelzang, Elizabeth E. Warfield, Mark J. Ratain & Richard L. Schilsky

  3. Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, 91010, Duarte, CA, USA

    James W. Raschko & James H. Doroshow

  4. Section of Hematology/Oncology, The University of Chicago Medical Center, 5841 S. Maryland Avenue, Box 420, 60637, Chicago, IL, USA

    Everett E. Vokes, Nicholas J. Vogelzang, Elizabeth E. Warfield, Mark J. Ratain & Richard L. Schilsky

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  1. Everett E. Vokes
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  2. James W. Raschko
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  4. Elizabeth E. Warfield
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  6. James H. Doroshow
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Additional information

Supported in part by a Fletcher Scholar award (to R. L. S.) M. J. R. is the recipient of a Clinical Oncology Career Development award from the American Cancer Society

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Vokes, E.E., Raschko, J.W., Vogelzang, N.J. et al. Five-day infusion of fluorodeoxyuridine with high-dose oral leucovorin: a phase I study. Cancer Chemother. Pharmacol. 28, 69–73 (1991). https://doi.org/10.1007/BF00684960

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  • DOI: https://doi.org/10.1007/BF00684960

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