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.
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Authors | F R Sattler, C J Allegra, T D Verdegem, B Akil, C U Tuazon, C Hughlett, D Ogata-Arakaki, J Feinberg, J Shelhamer, H C Lane |
Journal | The Journal of infectious diseases
(J Infect Dis)
Vol. 161
Issue 1
Pg. 91-6
(Jan 1990)
ISSN: 0022-1899 [Print] United States |
PMID | 2136905
(Publication Type: Journal Article)
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Chemical References |
- Quinazolines
- Leucovorin
- Trimetrexate
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Topics |
- Acquired Immunodeficiency Syndrome
(complications)
- Adult
- Dose-Response Relationship, Drug
- Drug Evaluation
- Drug Therapy, Combination
- Humans
- Leucovorin
(administration & dosage, adverse effects, therapeutic use)
- Male
- Pneumonia, Pneumocystis
(drug therapy, etiology)
- Quinazolines
(administration & dosage, adverse effects, therapeutic use)
- Trimetrexate
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