Trimetrexate-Leucovorin Dosage Evaluation Study for Treatmentof Pneumocystis carinii Pneumonia

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Abstract
Todetermine 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 received90 mg/m2 and 160 mg/m2, respectively. Leucovorin was increased twofold and trimetrexate reduced by 50% or suspended briefly for various levelsof neutropenia and thrombocytopenia until blood counts increased. Dosage-modifying hematologic toxicity occurred in 12 (46%), 8 (80%),9 (75%), and 4 (67%) patients in 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/m-zday 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.