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

Bibliographical note

Funding Information:
Received 28 September \993; revised 3\ January 1994. Presented in part: First International Congress of Drug Therapy in HIV Infection, November 1992. Glasgow. Scotland. Sattler F, Davis R. Frame P. Nichols L, Feinberg J. Trimetrexate versus trimethoprim-sulfamethoxazole for severe episodes of Pneumocvstis carinii pneumonia (PCP). AIDS 1992;6(suppl I):S8, 0-8A5. Institutional review board approval was obtained at each ofthe participating centers. and written informed consent was obtained from all study participants or their designated conservators. All investigators are members of the AIDS Clinical Trials Group and receive grant support through a cooperative agreement with the Division of AIDS, National Institutes of Health and University of Southern California (AI-6540). Reprints or correspondence: Dr. Fred R. Sattler. LAC-USC Medical Center. Rand Schrader Clinic, Rm. 349. 1175 N. Cummings St., Los Angeles, CA 90033. * Present affiliation: Division of General Medicine and Primary Care, Beth Israel Hospital, Boston. t Members are listed after text.

ASJC Scopus subject areas

  • General Medicine

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