OBJECTIVES:

• Compare the number of successful treatment outcomes among patients treated with caspofungin acetate vs amphotericin B liposomal for persistent fever and neutropenia following cancer therapy, in terms of survival for 7 days after study drug, resolution of fever, treatment of any baseline fungal infection, absence of breakthrough fungal infection during and for 7 days after study drug, and absence of study drug discontinuation due to toxicity or lack of efficacy.
• Compare the incidence of nephrotoxicity in patients treated with these regimens.
• Compare the incidence of infusion-related adverse events within 1 hour of the infusion in patients treated with these regimens.
• Compare the incidence of treatment discontinuation due to drug-related adverse events, frequency of drug-related events, number of breakthrough fungal infections, and number of successfully treated baseline fungal infections in patients treated with these regimens.
• Compare incidence of required dose increase due to inadequate clinical response in patients treated with these regimens.
• Compare the time to resolution of fever in patients treated with these regimens.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to high-risk (prior allogeneic bone marrow transplantation or prior chemotherapy for relapse of acute leukemia) vs low-risk and prior prophylactic antifungal therapy during chemotherapy (yes vs no). Patients are randomized to one of two treatment arms.

• Arm I: Patients receive caspofungin acetate IV over 1 hour followed by placebo IV over 2 hours.
• Arm II: Patients receive placebo IV over 1 hour followed by amphotericin B liposomal IV over 2 hours.

Treatment repeats daily for up to 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed at 7 and 14 days after study drug discontinuation.

PROJECTED ACCRUAL: A total of 1060 patients (530 per arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Leukemia, lymphoma, or other cancer that has been previously treated with chemotherapy or bone marrow or peripheral blood stem cell transplantation
• Absolute neutrophil count less than 500/mm^3 for past 96 hours and not expected to recover in next 48 hours
• Received at least 96 hours of parenteral systemic antibacterial therapy
• Fever greater than 38.0 degrees Celsius

• Adequately managed bacterial infection allowed if all of the following are true:

  • Negative blood cultures
  • Received at least 5 days of antibiotics to which any bacterial isolates are sensitive
  • Surgical drainage of any abscess fluid or surgical debridement of infected tissues
  • Removal of infected catheters
• No invasive fungal infection
• Not previously enrolled on this study

PATIENT CHARACTERISTICS:

Age:

• 16 and over

Performance status:

• Karnofsky 30-100%

Life expectancy:

• At least 5 days

Hematopoietic:

• Platelet count at least 5,000/mm^3
• INR no greater than 1.6 (no greater than 4.0 if receiving anticoagulants)

Hepatic:

• Bilirubin no greater than 3 times upper limit of normal (ULN)
• AST or ALT no greater than 5 times ULN
• Alkaline phosphatase no greater than 3 times ULN
• No acute hepatitis or cirrhosis

Renal:

• Not specified

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception
• No allergy, hypersensitivity, or prior serious reaction to any echinocandin antifungal or amphotericin B formulation
• No other condition or illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics

Chemotherapy:

• See Disease Characteristics
• No concurrent investigational antineoplastic therapy

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• At least 10 days since prior parenteral amphotericin B
• At least 14 days since prior investigational antibiotic, antifungal, or immunosuppressive drug
• No concurrent rifampin or cyclosporine
• No other concurrent investigational antibiotic, antifungal, or immunosuppressive drug
• No concurrent alcohol