Trimetrexate is a powerful inhibitor of the dihydrofolate reductase of Pneumocystis carinii. AIDS patients (n = 215) with moderate to severe P. carinii pneumonia were enrolled in a doubleblind study of trimetrexate plus leucovorin versus trimethoprim-sulfamethoxazole (TMP-SMZ) for 21 days. By study day 10, study therapy failed because of lack of efficacy in 16% of patients assigned to TMP-SMZ and 27% assigned to trimetrexate (P =.064), and the Pao2 Pao2 improved significantly faster with TMP-SMZ. By study day 21, failure rates were 20% with TMP-SMZ and 38% with trimetrexate (P =.008), with respective mortality rates of 12% and 20% (P =.088). By study day 49, the difference in mortality (16% vs. 31%) was significant (P =.028). The cumulative incidence of serious and treatment-terminating adverse events including hematologic toxicities was less with trimetrexate (P <.001). Thus, trimetrexate plus leucovorin was effective, albeit inferior to TMP-SMZ, Jor moderately severe P. carinii pneumonia but was better tolerated than TMP-SMZ.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Infectious Diseases