Abstract
Background: In a double-blind randomized trial of empirical antifungal Rx for persistently febrile neutropenic pts, CAS was as effective as and better tolerated than L-AmB. We now examine the results of this study in the subgroup of pts with AML.
Methods: Randomization to CAS (70 mg x 1, then 50 mg/d) or L-AmB (3 mg/kg/d) was stratified by risk category [high risk = allogeneic hematopoietic stem cell transplant or relapsed acute leukemia] and use of antifungal prophylaxis. The primary efficacy endpoint was % of treated pts with documented fever and neutropenia who had a successful outcome defined by all the following: successful Rx of baseline (BL) invasive fungal infection (IFI) (if any), no breakthrough (BT) IFI to 7 d post-Rx, survival @7d post-Rx, no premature discontinuation (DC) due to lack of efficacy or study drug toxicity, and fever resolution x 48 hr during neutropenia.
Results: 703/1095 (64%) of the treated pts had AML, including 364/556 (65%) and 339/539 (63%) in the CAS and L-AmB groups, respectively. Demographic characteristics were similar in AML pts in both Rx groups. 27% of CAS and 22% of L-AmB pts with AML were high risk. Median days of Rx were: CAS, 12; L-AmB, 11. The table shows % AML pts with a successful outcome by Rx group.
% AML pts with a successful outcome by Rx group
| . | CAS (N=364) . | L-AmB (N=339) . | Difference (CAS - L-AmB) . | 95% CI for difference between treatment groups . |
|---|---|---|---|---|
| † 7/14 CAS and 5/16 L-AmB pts had successful Rx of BL IFI. | ||||
| Success Rx of BL IFI † | 50 | 31 | 19 | (−16, 53) |
| No BT IFI | 93 | 95 | −2 | (−5, 2) |
| Suvival @ 7d post-Rx | 92 | 88 | 4 | (0, 8) |
| No premature DC | 87 | 86 | 2 | (−3, 7) |
| Fever resolution | 48 | 46 | 2 | (−5, 9) |
| All of the above | 40 | 38 | 2 | (−5, 10) |
| . | CAS (N=364) . | L-AmB (N=339) . | Difference (CAS - L-AmB) . | 95% CI for difference between treatment groups . |
|---|---|---|---|---|
| † 7/14 CAS and 5/16 L-AmB pts had successful Rx of BL IFI. | ||||
| Success Rx of BL IFI † | 50 | 31 | 19 | (−16, 53) |
| No BT IFI | 93 | 95 | −2 | (−5, 2) |
| Suvival @ 7d post-Rx | 92 | 88 | 4 | (0, 8) |
| No premature DC | 87 | 86 | 2 | (−3, 7) |
| Fever resolution | 48 | 46 | 2 | (−5, 9) |
| All of the above | 40 | 38 | 2 | (−5, 10) |
The composite success rates for the high risk AML pts were 46/99 (46%) for CAS and 31/76 (41%) for L-AmB.
Conclusions: In this post hoc subgroup analysis, CAS provided an effective and generally well-tolerated option for the empirical Rx of persistently febrile neutropenic pts with AML.
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