Amphotericin B colloidal dispersion (ABCD; Amphocil) was evaluated in a phase I dose-escalation study in 75 marrow transplant patients with invasive fungal infections (primarily Aspergillus or Candida species) to determine the toxicity profile, maximum tolerated dose, and clinical response. Escalating doses of 0.5-8.0 mg/kg in 0.5-mg/kg/patient increments were given up to 6 weeks. No infusion-related toxicities were observed in 32% of the patients; 52% had grade 2 and 5% had grade 3 toxicity. No appreciable renal toxicity was observed at any dose level. The estimated maximum tolerated dose was 7.5 mg/kg, defined by rigors and chills and hypotension in 3 of 5 patients at 8.0 mg/kg. The complete or partial response rate across dose levels and infection types was 52%. For specific types of infections, 53% of patients with fungemia had complete responses, and 52% of patients with pneumonia had complete or partial responses. ABCD was safe at doses to 7.5 mg/kg and had tolerable infusion-related toxicity and demonstrate antifungal activity.
Bibliographical noteFunding Information:
Received 19 April 1995; revised 13 December 1995. All patients gave informed consent according to the guidelines of the Fred Hutchinson Cancer Research Center Institutional Review Board. Grant support: National Institutes of Health (CA-18029, CA-15704, and HL-3644); Sequus Pharmaceuticals, Reprints or correspondence: Dr. Raleigh A. Bowden, Infectious Diseases, Box 358080, Fred Hutchinson Cancer Research Center, 1124 Columbia St., Seattle, WA 98104-2092.