Cancer Chemotherapy and Pharmacology

, Volume 28, Issue 1, pp 69–73 | Cite as

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

  • Everett E. Vokes
  • James W. Raschko
  • Nicholas J. Vogelzang
  • Elizabeth E. Warfield
  • Mark J. Ratain
  • James H. Doroshow
  • Richard L. Schilsky
Original Articles Oral Leucovorin, Fluorodeoxyrudine, Infusion

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.

Keywords

Renal Cell Carcinoma Intravenous Infusion Evaluable Patient Hematologic Toxicity Skin Rash 

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Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • Everett E. Vokes
    • 4
    • 1
    • 2
  • James W. Raschko
    • 3
  • Nicholas J. Vogelzang
    • 4
    • 1
    • 2
  • Elizabeth E. Warfield
    • 4
    • 1
    • 2
  • Mark J. Ratain
    • 4
    • 1
    • 2
  • James H. Doroshow
    • 3
  • Richard L. Schilsky
    • 4
    • 1
    • 2
  1. 1.Department of Radiation and Cellular OncologyThe University of Chicago Pritzker School of MedicineChicagoUSA
  2. 2.Committee on Clinical PharmacologyThe University of Chicago Pritzker School of MedicineChicagoUSA
  3. 3.Department of Medical Oncology and Therapeutics ResearchCity of Hope National Medical CenterDuarteUSA
  4. 4.Section of Hematology/OncologyThe University of Chicago Medical CenterChicagoUSA

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