Table 2.
Summary of clinical trials comparing efficacy and safety of liposomal amphotericin B with other antifungal agents for empirical antifungal therapy in patients with neutropenia
| Reference/type of study | Treatment regimen (dose) | Number of patients | Mean age (range) | Patient population (% of patients) | Mean duration of treatment | Renal toxicity‡ (% of patients) | Infusion related reactions† (% of patients) | Treatment success rate* (% of patients) | Comments |
|---|---|---|---|---|---|---|---|---|---|
| Walsh47 Randomized, double blind, multicenter clinical trial |
L-AmB (3 mg/k/d) | 343 | 41 (2–79) | HSCT: 45% Non-HSCT: 55% |
10.8 days | 19% | 17%§ | 50.1% [95% CI: 45–56] | L-AMB was associated with significant reduction of breakthrough infections (mostly non-albicans Candida infections) |
| Amb-D (0.6 mg/kg/d) | 344 | 42 (2–80) | HSCT: 47% Non-HSCT: 53% |
10.3 days | 34% (P < 0.001) | 44%§ (P < 0.001) | 49.4% [95% CI: 44–55] | ||
| Wingard45 Randomized, double blind, multicenter clinical trial |
L-AmB (3 mg/kg/d) | 85 | 41.4 (3–74) | HSCT: 46% Non-HSCT: 54% |
8 days | 14.1% | 51.8%1 | 40% | Study designed to detect differences in toxicity, not efficacy. Breakthrough infection rates were similar in three groups. |
| L-AmB (5 mg/kg/d) | 81 | 42 (2–84) | HSCT: 49% Non-HSCT: 51% |
8 days | 14.8% | 48.1%1 | 42% | ||
| ABLC (5 mg/kg/d) | 78 | 42.8 (2–76) | BMT: 51% Non-BMT: 49% |
8 days | 42.3% (P ≤ 0.01) | 88.5%1 (P ≤ 0.001) | 33.3% | ||
| Walsh51 Randomized, open labeled, multicenter clinical trial |
Voriconazole 6 mg/kg IV Q12 h on day 1, then 3 mg/kg IV Q12 h or 200 mg PO after at least 3 days of IV therapy | 415 | 46.3 (12–82) | HSCT: 47.7% | 7 days | With concomitant Nephrotoxic drugs¶: 0–1 drugs: 11.3% ≥2 drugs: 14.3% ≥3 drugs: 50% |
Abnormal vision 22% Flushing 3.4% Chills 13.7% |
26% | Breakthrough IFI occurred in 8 patients on voriconazole and 21 patients on L-AmB (P = 0.02). Hepatotoxicity was similar in both groups. |
| L-AmB (3 mg/kg/d) | 422 | 45 (12–80) | HSCT: 51.4% | 7 days | With concomitant Nephrotoxic drugs¶: 0–1 drugs: 9.7% ≥2 drugs: 39% ≥3 drugs: 60% (P < 0.001) |
Abnormal vision 0.7% Flushing 10.9% Chills 29.9% (P < 0.001) |
30.6% | ||
| Walsh48 Randomized, double blind, multicenter clinical trial |
Caspofungin (70 mg in day 1 and then 50 mg/d) | 556 | 51 (17–83) | Acute leukemia: 75.8% (Allo-HSCT: 6.5%) | 13 days | 2.6% | 47% | 33.9% | Most patients included in the study had acute leukemia. |
| L-AmB (3 mg/kg/d) | 539 | 49 (16–83) | Acute leukemia: 72.2% (Allo-HSCT: 7.2%) | 12.5 days | 11.5% (P < 0.001) | 59% (P < 0.001) | 33.7% | Breakthrough infections were similar in both groups. | |
| Maertens49 Randomized, double blind, multicenter clinical trial |
Caspofungin (70 mg/m2 on day 1, then 50 mg/m2 daily) | 56 | 6 (2–16) | Acute leukemia: 60.7% (Allo-HSCT: 10.7%) | 11.6 days | 5.5% | 48.2% [95% CI: 34.7–62.0] | 46.6% [95% CI: 33.5–59.6] | Study conducted exclusively in pediatric population. |
| L-AmB (3 mg/kg/d) | 26 | 5.5 (2–16) | Acute leukemia: 65.4% (Allo-HSCT: 65.4%) | 11.4 days | 8% | 46.2% [95% CI: 26.6–66.6] | 32.2% [95% CI: 13.9–50.5] | Limitation: small sample. Only 1 patient in L-AmB group had breakthrough infection. |
Notes: Infusion related reactions include fevers, chills, hypotension, chest pain, tachycardia, etc;
nephrotoxic effect was defined by an elevation in the serum creatinine level to more than 1.5 times the base-line value;
treatment success rate was determined by a composite outcome score consisting of five criteria: (1) successful treatment of any baseline fungal infection, (2) absence of any breakthrough fungal infection during therapy or within seven days after the completion of therapy, (3) survival for 7 days after the completion of therapy, (4) no premature discontinuation of study therapy because of drug related toxicity or lack of efficacy, and (5) resolution of fever during neutropenia. Treatment was considered successful if all five criteria were met.
Infusion-related reactions on day 1 study drug infusion;
fevers within 1 hour of drug infusion (increase of ≥1.0°C); overall rate of infusion-related reactions was not provided;
nephrotoxic drugs were aminoglycosides, cyclosporine, and foscarnet.
Abbreviations: ABLC, amphotericin B lipid complex; AmB-D, amphotericin B deoxycolate; CI, confidence interval; L-AmB, liposomal amphotericin B; BMT, bone marrow transplant; Allo, allogeneic; HSCT, hematological stem cell transplant.