title: Trimetrexate-leucovorin dosage evaluation study for treatment of Pneumocystis carinii pneumonia.
abstract: To determine the maximal tolerable dosage of trimetrexate for treatment of pneumocystis pneumonia, 25 patients were treated each day with 45 mg/m2 of trimetrexate and 80 mg/m2 of leucovorin; 10 received 60 mg/m2 and 80 mg/m2; 12 received 60 mg/m2 and 160 mg/m2; and 6 received 90 mg/m2 and 160 mg/m2, respectively. Leucovorin was increased twofold and trimetrexate reduced by 50% or suspended briefly for various levels of neutropenia and thrombocytopenia until blood counts increased. Dosage-modifying hematologic toxicity occurred in 12 (46%), 8 (80%), 9 (75%), and 4 (67%) patients with the respective groups. Cytopenias were in each case reversible and other toxicities were well tolerated. All survivors but one were able to receive a full 21 doses of trimetrexate. Twenty-four (92%), 10 (100%), 7 (58%), and 4 (80%) of patients in the respective groups survived. Thus, the 45 mg/m2/day dosage of trimetrexate with 80 mg/m2/day of leucovorin resulted in the least dosage-modifying toxicity and excellent efficacy. This combination should be selected for studies to compare trimetrexate with other therapies for pneumocystis pneumonia.
authors: Los Angeles County-University of Southern California Medical Center 90033.
authors: F R
authors: FR
authors: Sattler
authors: C J
authors: CJ
authors: Allegra
authors: T D
authors: TD
authors: Verdegem
authors: B
authors: B
authors: Akil
authors: C U
authors: CU
authors: Tuazon
authors: C
authors: C
authors: Hughlett
authors: D
authors: D
authors: Ogata-Arakaki
authors: J
authors: J
authors: Feinberg
authors: J
authors: J
authors: Shelhamer
authors: H C
authors: HC
authors: Lane
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy* / Q000209:etiology; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016597:Trimetrexate
chemical_list: D011799:Quinazolines; D002955:Leucovorin; D016597:Trimetrexate