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Trimetrexate-Leucovorin Dosage Evaluation Study for Treatment of Pneumocystis carinii Pneumonia

Fred R. Sattler, Carmen J. Allegra, Thomas D. Verdegem, Bisher Akil, Carmelita U. Tuazon, Claire Hughlett, Debra Ogata-Arakaki, Judith Feinberg, James Shelhamer, H. Clifford Lane, Roger Davis, C. Thomas Boylen, John M. Leedom and Henry Masur
The Journal of Infectious Diseases
Vol. 161, No. 1 (Jan., 1990), pp. 91-96
Published by: Oxford University Press
Stable URL: http://www.jstor.org/stable/30119629
Page Count: 6
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Trimetrexate-Leucovorin Dosage Evaluation Study for Treatment of Pneumocystis carinii Pneumonia
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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 5096 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 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/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.

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