Safety and toxicity of amphotericin B in glucose 5% or intralipid 20% in neutropenic patients with pneumonia or fever of unknown origin: randomised study.
OBJECTIVE
To compare the feasibility of treatment, safety, and toxicity of intravenous amphotericin B deoxycholate prepared in either glucose or intralipid for empirical antimycotic treatment of neutropenic cancer patients.


METHODS
Single centre stratified, randomised non-blinded phase II study.


METHODS
University hospital providing tertiary clinical care.


METHODS
51 neutropenic patients (leukaemia (35), lymphoma (11), solid tumours (5)) with refractory fever of unknown origin (24) or pneumonia (27).


METHODS
Amphotericin B 0.75 mg/kg/day in 250 ml glucose 5% solution or mixed with 250 ml intralipid 20%, given on eight consecutive days then alternate days, as a 1-4 hour infusion.


METHODS
Feasibility of treatment, subjective tolerance (questionnaire), and objective toxicity (common toxicity criteria of the National Cancer Institute).


RESULTS
Study arms were balanced for age, sex, underlying malignancy, renal and liver function, and pre- and concomitant treatment with antibiotics and nephrotoxic agents. No statistically significant or clinically relevant differences were found between the treatment groups for: daily or cumulative dose and duration of treatment with amphotericin B; incidence and time of dose modifications or infusion duration changes related to toxicity; dose or duration of symptomatic support with opiates, antipyretics, or antihistamines; renal function; subjective tolerance; most common toxicity scores; course of infection; and incidence of treatment failures. Patients treated with amphotericin B in intralipid were given fewer diuretics (P<0.05) and therefore had more peripheral oedema (P<0.01) and needed less potassium supplementation (P<0.05) than patients given amphotericin in glucose. Acute respiratory events were more common in the intralipid arm (P<0.05).


CONCLUSIONS
Amphotericin B 0.75 mg/kg/day in intralipid given on eight consecutive days then alternate days provides no benefit and is associated with potential pulmonary side effects possibly because of fat overload or an incompatibility of the two drugs.
Department of Haematology/Oncology, Hanover University Medical School, D-30625 Hanover, Germany. Patrick_Schoffski@compuserve.com
P
P
Schöffski
M
M
Freund
R
R
Wunder
D
D
Petersen
C H
CH
Köhne
H
H
Hecker
U
U
Schubert
A
A
Ganser
D000293:Adolescent; D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry; D004337:Drug Carriers; D004339:Drug Compounding; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage; D005240:Feasibility Studies; D005260:Female; D005335:Fever of Unknown Origin / Q000150:complications / Q000188:drug therapy*; D005947:Glucose / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000150:complications*; D011014:Pneumonia / Q000150:complications / Q000188:drug therapy*; D011446:Prospective Studies
D000935:Antifungal Agents; D004337:Drug Carriers; D005217:Fat Emulsions, Intravenous; D000666:Amphotericin B; D005947:Glucose