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

J Infect Dis. 1994 Jul;170(1):165-72. doi: 10.1093/infdis/170.1.165.

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 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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS-Related Opportunistic Infections / drug therapy*
  • AIDS-Related Opportunistic Infections / mortality
  • Adolescent
  • Adult
  • Child
  • Clinical Protocols
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Leucovorin / adverse effects
  • Leucovorin / therapeutic use*
  • Male
  • Middle Aged
  • Multicenter Studies as Topic
  • Pneumonia, Pneumocystis / complications
  • Pneumonia, Pneumocystis / drug therapy*
  • Pneumonia, Pneumocystis / mortality
  • Prospective Studies
  • Sulfamethoxazole / adverse effects
  • Sulfamethoxazole / therapeutic use*
  • Treatment Outcome
  • Trimethoprim / adverse effects
  • Trimethoprim / therapeutic use*
  • Trimetrexate / adverse effects
  • Trimetrexate / therapeutic use*

Substances

  • Trimethoprim
  • Sulfamethoxazole
  • Leucovorin
  • Trimetrexate