Phase I study of piritrexim and gemcitabine in patients with advanced solid tumors

Michael Huie, Michael Carducci, Glenn Liu, George Wilding, Rebecca Marnocha, Miguel Izquierda, James Thomas

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: In this phase I study, the combination of piritrexim and gemcitabine was given to establish the maximum tolerated dose and the recommended phase II dose, and to determine a toxicity and efficacy profile. Methods: Fifty-two patients with normal and impaired renal function were enrolled on this phase I study. The starting dose was piritrexim 10 mg 3 times daily (5 days of the week for 3 weeks and 1 week off each 28-day cycle) and gemcitabine 1000 mg/m2 on days 1, 8, and 15. The piritrexim was escalated in a stepwise fashion with this dose of gemcitabine and then with gemcitabine 1000 mg/m2 for days 1 and 15. Results: The recommended phase II dose of this combination was felt to be piritrexim 50 mg/day (10 mg every morning, 20 mg every noon, and 20 mg every evening) with gemcitabine 1000 mg/m2 on days 1, 8, and 15, and piritrexim 75 mg/day (25 mg thrice daily) with gemcitabine 1000 mg/m2 on days 1 and 15. Neutropenia and thrombocytopenia were the most often reported toxicity. Dose-limiting toxicity was thrombocytopenia in both groups. The number of renal-impaired patients enrolled was too small to establish a maximum tolerated dose for this group (piritrexim became unavailable), but the combination was tolerated in the patients with impaired renal dysfunction. There was 1 complete response, 1 partial response, and 1 minimal response. Conclusion: The combination of piritrexim and gemcitabine was determined to be tolerable in heavily pretreated patients for use in solid tumors.

Original languageEnglish (US)
Pages (from-to)613-617
Number of pages5
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume28
Issue number6
DOIs
StatePublished - Dec 1 2005

Keywords

  • Antifolate
  • Antimetabolite
  • Cancer
  • Chemotherapy
  • Phase I

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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