Trimetrexate with leucovorin versus trimethoprim-sulfamethoxazole for moderate to severe episodes of pneumocystis carinii pneumonia in patients with aids: A prospective, controlled multicenter investigation of the aids clinical trials group protocol 029/031

Fred R. Sattler, Peter Frame, Roger Davis, Larry Nichols, Brent Shelton, Bisher Akil, Robert Baughman, Claire Hughlett, Walter Weiss, Charles Van der Horst, John Black, William Powderly, Roy T. Steigbigel, John M. Leedom, Henry Masur, Judith Feinberg, Eyster Elaine, S. Milton, Gocke David, Beck KeithLederman Michael, Phair John, Reichman Richard, S. Sacks Henry

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    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)165-172
    Number of pages8
    JournalJournal of Infectious Diseases
    Volume170
    Issue number1
    DOIs
    StatePublished - Jul 1994

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Infectious Diseases

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