Antifungal prophylaxis during remission induction therapy for acute leukemia fluconazole versus intravenous amphotericin B.
BACKGROUND
Fungal infection is a frequent and often fatal complication in patients undergoing remission induction therapy for acute leukemia. Although candidiasis is the most common infection, mold infections are increasing in frequency. Fluconazole (FLU) is a new antifungal agent that has been used successfully to treat Candida infections and has modest activity against aspergillosis in animal models. Subtherapeutic doses of amphotericin B (AMB) have been considered effective as prophylaxis in these patients. This study was designed to compare the efficacy and toxicity of these agents as antifungal prophylaxis.


METHODS
Adults with acute leukemia undergoing remission induction chemotherapy randomly were assigned to receive antifungal prophylaxis with AMB (0.5 mg/kg three times weekly) or FLU (400 mg daily). Trimethoprim-sulfamethoxazole was administered as an antibacterial prophylaxis. Prophylaxis was continued until the patient achieved complete remission or was treated for 8 weeks without antileukemic response. Prophylaxis was discontinued if the patient experienced a possible or proven fungal infection or a serious toxicity.


RESULTS
Overall, 58% of the 36 patients assigned to AMB successfully completed prophylaxis compared with 80% of the 41 patients assigned to FLU (< 0.05). Proven, probable, or possible fungal infections occurred in 31% and 17% of the patients, respectively. The risk of discontinuing prophylaxis due to fungal infection or toxicity increased with time in the study and was significantly greater for AMB (P = 0.02).


CONCLUSIONS
At the dose used in this study, AMB was no more effective and was more toxic than FLU for prophylaxis of fungal infections in patients undergoing remission induction chemotherapy for acute leukemia.
Bodey
G P
GP
Department of Medical Specialties, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Anaissie
E J
EJ
Elting
L S
LS
Estey
E
E
O'Brien
S
S
Kantarjian
H
H
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000666:Amphotericin B / Q000009:adverse effects / Q000627:therapeutic use*; D001752:Blast Crisis / Q000188:drug therapy / Q000382:microbiology; D005260:Female; D015725:Fluconazole / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced; D007938:Leukemia / Q000188:drug therapy* / Q000382:microbiology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000517:prevention & control*; D011292:Premedication; D011446:Prospective Studies; D012074:Remission Induction
D000666:Amphotericin B; D015725:Fluconazole