Amphotericin B Lipid Complex Effective, Less Toxic

SAN FRANCISCO-Amphotericin B lipid complex may be the treatmentof choice for patients with hematogenous or invasive candidiasis,Elias J. Anaissie, MD, said at the 35th Interscience Conferenceon Antimicrobial Agents and Chemotherapy (ICAAC).

In the first large randomized comparative trial of a lipid amphotericinB product vs standard amphotericin B for the treatment of candidiasis,amphotericin B lipid complex was as effective as standard ampho-tericinB, with the advantage of being less nephrotoxic, said Dr. Anaissie,associate professor of medicine, Infectious Diseases Section,University of Texas M.D. Anderson Cancer Center.

Invasive Candida infections have emerged as a major causeof morbidity and mortality in immunocompromised patients, Dr.Anaissie said. Amphotericin B has, until recently, been the mainstayof treatment for invasive fungal infections because of its broadspectrum of activity. Its therapeutic utility is limited, however,by dose-limiting toxicities, particularly nephrotoxicity.

Amphotericin B lipid complex, from The Liposome Company, Princeton,NJ, is a novel amphotericin B preparation complex with two lipidsin a 1:1 drug-to-lipid ratio.

A prospective, randomized, multicen-ter trial was set up to comparethe efficacy and safety of the two amphotericin B products astreatment for invasive candi-diasis, Dr. Anaissie said.

In a 27-center study, 231 patients with hematogenous or organinfection caused by Candida species, 50% of whom had cancer,were randomly assigned to receive amphotericin B lipid complex,5 mg/kg/day, or standard amphotericin B, 1 mg/kg/day, for a medianduration of 14 days.

A two-to-one randomization was used, with 153 persons receivingampho-tericin B lipid complex, and 78 patients receiving standardamphotericin B. The most common diagnosis was hematogenous candidiasis(84%); Calbicans accounted for 51% of the infections,and the remaining cases were caused by a wide variety of Candidaspecies.

Response Rates

The overall response rates were similar in both groups: 65% for124 evaluable patients treated with amphotericin B lipid complexand 61% for 70 evaluable individuals in the standard amphotericinB group, Dr. Anaissie said.

Lower response rates were observed in neutropenic vs non-neutropenicpatients, in individuals with hematologic malignancies vs solidtumors, and in patients in whom catheters remained in place vsthose in whom catheters were removed, but these differences werenot statistically significant.

Mycologic eradication rates were also similar: 88% for patientsreceiving amphotericin B lipid complex, and 87% for patients receivingstandard ampho-tericin B.

At 3-month follow-up, Dr Anaissie said, there were no significantdifferen-ces in relapse or survival, with 60% of those on amphotericinB lipid complex remaining alive, compared with 51% of patientsreceiving standard amphotericin B. Median survival was 134 daysfor amphotericin B lipid complex patients vs 61 days for patientswho received standard amphotericin B, a positive trend in favorof amphotericin B lipid complex therapy, but not statisticallysignificant.

Safety Profiles

The major differences in the two treatment approaches were seenin the safety profiles, Dr. Anaissie said. Based on assessmentof renal function, amphotericin B lipid complex was less nephrotoxicthan standard amphotericin B.

Baseline serum creatinine doubled in 47% of patients treated withthe standard agent vs 28% of patients receiving the lipid complex.

Using Kaplan-Meier analysis, Dr. Anaissie said, the median numberof days to doubling of the serum creatinine level was 19 daysfor patients in the standard amphotericin B group, and 82 daysfor patients receiving amphotericin B lipid complex.

The most common reason for withdrawal of patients from the studywas nephrotoxicity, Dr. Anaissie said. Overall, 15 (19%) of 78patients in the standard amphotericin B group discontinued therapyvs 12 (8%) of 153 patients who were receiving amphotericin B lipidcomplex.