Effectiveness of an oral triazole for opportunistic mold infections in patients with cancer: experience with SCH 39304.
Fungal infections are the most common infectious cause of death among patients with hematologic malignancies. Conventional antifungal agents have limited activity and a narrow therapeutic index. In an open-label study we assessed the activity of an oral triazole, SCH 39304, in the treatment of refractory life-threatening mold infections in 50 patients with cancer, most of whom had previously received amphotericin B and/or fluconazole. SCH 39304 was given at a daily dose of 200-400 mg for a median of 8 weeks. The overall rate of response was 79% among 34 evaluable patients, with a complete response in 22 instances and a partial response in 5. Some patients responded despite persistent, profound immunosuppression. Three patients developed relapses, and two developed fungal superinfections. SCH 39304 was well tolerated. We conclude that oral triazoles such as SCH 39304 may represent effective and safe treatment of mold infections in immunosuppressed patients, at least after standard antifungal chemotherapy. Unfortunately, the carcinogenic potential of SCH 39304 in animals has precluded its development. Our hope is that analogues with similar efficacy but without carcinogenic potential can be developed.
Anaissie
E J
EJ
Department of Medical Specialties, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Kontoyiannis
D P
DP
Vartivarian
S
S
Kantarjian
H M
HM
O'Brien
S
S
Giralt
S A
SA
Andersson
B S
BS
Karl
C
C
Champlin
R E
RE
Bodey
G P
GP
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007938:Leukemia / Q000150:complications; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000150:complications / Q000188:drug therapy*; D009369:Neoplasms / Q000150:complications; D009894:Opportunistic Infections / Q000150:complications / Q000188:drug therapy*; D011446:Prospective Studies; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000935:Antifungal Agents; D014230:Triazoles; C056513:Sch 39304