Salvage trial of trimetrexate-leucovorin for the treatment of cerebral toxoplasmosis in patients with AIDS.
The clinical efficacy of trimetrexate, a dihydrofolate reductase inhibitor with potent in vitro antitoxoplasma activity, was assessed in 9 sulfonamide-intolerant patients with AIDS and biopsy-proven cerebral toxoplasmosis. The 9 patients were treated for 28-149 days with trimetrexate (30-280 mg/m2/day) plus leucovorin (20-90 mg/m2 every 6 h). Radiographic responses were documented in 8 patients, and clinical responses in 5 patients. Despite continued therapy, all patients deteriorated clinically and radiographically within 13-109 days of their initial improvement. Trimetrexate at very high doses for extended periods was not associated with serious toxicity. Trimetrexate alone had dramatic but transient activity in sulfonamide-intolerant patients and thus is not adequate as single-agent therapy for AIDS-associated toxoplasmosis.
Masur
H
H
National Institutes of Health, Bethesda, MD 20892.
Polis
M A
MA
Tuazon
C U
CU
Ogata-Arakaki
D
D
Kovacs
J A
JA
Katz
D
D
Hilt
D
D
Simmons
T
T
Feuerstein
I
I
Lundgren
B
B
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D000293:Adolescent; D000328:Adult; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use*; D008297:Male; D014057:Tomography, X-Ray Computed; D016781:Toxoplasmosis, Cerebral / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D016597:Trimetrexate / Q000627:therapeutic use*
D002955:Leucovorin; D016597:Trimetrexate