Background: Invasive fungal infection (IFI) is an increasing source of morbidity and mortality in cancer patients, particularly those with severe neutropenia or undergoing transplantation. Despite a scarcity of powerful clinical trials, use of antifungal prophylaxis is widespread. A systematic review of the available data is needed for evidence based clinical decision making. Methods: Data bases (Medline, Cancerlit) and conferences (ICAAC, IDSA, ASH, ASCO, ECCMID) were searched for clinical trials on primary antifungal prophylaxis. Criteria proposed by the Infectious Diseases Society of America (Kish 2002) were used to establish recommendations. Additionally, relative risks (RR) were calculated. Results: We identified 39 clinical trials reporting 8434 patients published 1987-2002. Underlying diseases were: 5288 (62.7%) leukemia, 842 (10%) lymphoma, 2304 (27.3%) other. Allogeneic or autologous stem cell transplantation were performed in 1664 (19.7%) and 1272 (15.1%) pts. Proven IFI according to EORTC/MSG criteria occurred in 425 (5%) pts. These were due to Aspergillus spp (n=170, 40%), Candida spp (n=205, 48.2%), or other species (n=50, 11.8%). There were 4395 (52.1%) pts on active oral systemic treatment and 1372 (16.3%) on placebo. Overall mortality was 11.6% (979 pts); 246 (25.1%) pts deaths were attributable to IFI and 733 (74.9%) to other reasons. For placebo vs active absorbable treatment RR of IFI was 2.1 and RR of death was 2.15. For fluconazole 400mg qd vs placebo RR of IFI and death were 2.4 and 2.6. For itraconazole oral suspension the RR for IFI and death were 2.4 and 5.3. Conclusions: In our analysis, fluconazole 400mg qd and itraconazole oral suspension reduced incidences of IFI and mortality in cancer patients as compared to placebo (Level A1). Based on the assessment of the literature, we found no evidence against the use of antifungal prophylaxis (Level D & E).
Full conference title:
- ICAAC 42nd