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

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.

• Authors: Michael Huie, Michael Carducci, Glenn Liu, George Wilding, Rebecca Marnocha, Miguel Izquierda, James Thomas
• Journal: American journal of clinical oncology (Am J Clin Oncol) Vol. 28 Issue 6 Pg. 613-7 (Dec 2005) ISSN: 1537-453X [Electronic] United States
• PMID: 16317274 (Publication Type: Clinical Trial, Phase I, Comparative Study, Journal Article, Multicenter Study)

Chemical References

• Antimetabolites, Antineoplastic
• Folic Acid Antagonists
• Pyrimidines
• Deoxycytidine
• piritrexim
• Gemcitabine

Topics

• Administration, Oral
• Adult
• Aged
• Antimetabolites, Antineoplastic (administration & dosage, adverse effects, pharmacology)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, pharmacology, therapeutic use)
• Combined Modality Therapy
• Deoxycytidine (administration & dosage, adverse effects, analogs & derivatives, pharmacology)
• Drug Synergism
• Female
• Folic Acid Antagonists (administration & dosage, adverse effects, pharmacology)
• Gastrointestinal Diseases (chemically induced)
• Hematologic Diseases (chemically induced)
• Humans
• Kidney (physiopathology)
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasms (drug therapy)
• Pyrimidines (administration & dosage, adverse effects, pharmacology)
• Salvage Therapy
• Treatment Outcome
• Gemcitabine