Document 0849
 DOCN  M9470849
 TI    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.
 DT    9409
 AU    Sattler FR; Frame P; Davis R; Nichols L; Shelton B; Akil B; Baughman R;
       Hughlett C; Weiss W; Boylen CT; et al; Department of Medicine, Los
       Angeles County-University of Southern; California Medical Center 90033.
 SO    J Infect Dis. 1994 Jul;170(1):165-72. Unique Identifier : AIDSLINE
       MED/94284632
 AB    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 double-blind 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, for moderately
       severe P. carinii pneumonia but was better tolerated than TMP-SMZ.
 DE    Adolescence  Adult  AIDS-Related Opportunistic Infections/*DRUG
       THERAPY/MORTALITY  Child  Clinical Protocols  Double-Blind Method  Drug
       Therapy, Combination  Female  Human  Leucovorin/ADVERSE
       EFFECTS/*THERAPEUTIC USE  Male  Middle Age  Multicenter Studies
       Pneumonia, Pneumocystis carinii/COMPLICATIONS/*DRUG THERAPY/  MORTALITY
       Prospective Studies  Sulfamethoxazole/ADVERSE EFFECTS/*THERAPEUTIC USE
       Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  Treatment Outcome
       Trimethoprim/ADVERSE EFFECTS/*THERAPEUTIC USE  Trimetrexate/ADVERSE
       EFFECTS/*THERAPEUTIC USE  CLINICAL TRIAL  JOURNAL ARTICLE  RANDOMIZED
       CONTROLLED TRIAL

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).