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.
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.
Department of Medicine, Los Angeles County-University of Southern California Medical Center 90033.
F R
FR
Sattler
P
P
Frame
R
R
Davis
L
L
Nichols
B
B
Shelton
B
B
Akil
R
R
Baughman
C
C
Hughlett
W
W
Weiss
C T
CT
Boylen
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000401:mortality; D000293:Adolescent; D000328:Adult; D002648:Child; D002985:Clinical Protocols; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D011020:Pneumonia, Pneumocystis / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D011446:Prospective Studies; D013420:Sulfamethoxazole / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014295:Trimethoprim / Q000009:adverse effects / Q000627:therapeutic use*; D016597:Trimetrexate / Q000009:adverse effects / Q000627:therapeutic use*
D014295:Trimethoprim; D013420:Sulfamethoxazole; D002955:Leucovorin; D016597:Trimetrexate