TY - JOUR
T1 - Trimetrexate with leucovorin versus trimethoprim-sulfamethoxazole for moderate to severe episodes of pneumocystis carinii pneumonia in patients with aids
T2 - A prospective, controlled multicenter investigation of the aids clinical trials group protocol 029/031
AU - Sattler, Fred R.
AU - Frame, Peter
AU - Davis, Roger
AU - Nichols, Larry
AU - Shelton, Brent
AU - Akil, Bisher
AU - Baughman, Robert
AU - Hughlett, Claire
AU - Weiss, Walter
AU - Van der Horst, Charles
AU - Black, John
AU - Powderly, William
AU - Steigbigel, Roy T.
AU - Leedom, John M.
AU - Masur, Henry
AU - Feinberg, Judith
AU - Elaine, Eyster
AU - Milton, S.
AU - David, Gocke
AU - Keith, Beck
AU - Michael, Lederman
AU - John, Phair
AU - Richard, Reichman
AU - Henry, S. Sacks
N1 - 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.
PY - 1994/7
Y1 - 1994/7
N2 - 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.
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 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.
UR - http://www.scopus.com/inward/record.url?scp=0028364088&partnerID=8YFLogxK
U2 - 10.1093/infdis/170.1.165
DO - 10.1093/infdis/170.1.165
M3 - Article
C2 - 8014493
AN - SCOPUS:0028364088
SN - 0022-1899
VL - 170
SP - 165
EP - 172
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 1
ER -