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


CONCLUSIONS
The combination of piritrexim and gemcitabine was determined to be tolerable in heavily pretreated patients for use in solid tumors.
Huie
Michael
M
University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin, USA. michael.huie@uwmf.wisc.edu
Carducci
Michael
M
Liu
Glenn
G
Wilding
George
G
Marnocha
Rebecca
R
Izquierda
Miguel
M
Thomas
James
J
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D005493:Folic Acid Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D016879:Salvage Therapy; D016896:Treatment Outcome; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D005493:Folic Acid Antagonists; D011743:Pyrimidines; D003841:Deoxycytidine; C024530:piritrexim; D000093542:Gemcitabine