Levofloxacin Compared With Cefepime in Treating Cancer Patients With Fever and Neutropenia
Levofloxacin Compared With Cefepime in Treating Cancer Patients With Fever and Neutropenia
RATIONALE: Levofloxacin may be effective in reducing fever and controlling other symptoms of
 neutropenia in patients who are being treated for cancer. It is not yet known whether
 levofloxacin is more effective than cefepime in reducing fever and controlling symptoms of
 neutropenia.

 PURPOSE: Randomized phase III trial to compare the effectiveness of levofloxacin with that of
 cefepime in reducing fever and controlling symptoms of neutropenia in patients who are being
 treated for cancer.
OBJECTIVES: I. Compare the safety and efficacy of levofloxacin versus cefepime in cancer
 patients with fever and neutropenia. II. Compare the percentage of patients whose fever
 defervesces and who have no signs or symptoms of infection with and without therapeutic
 modification. III. Compare the percentage of survival of patients treated with these 2
 regimens with no therapeutic modifications. IV. Compare the overall survival of patients
 treated with these 2 regimens regardless of therapeutic modifications. V. Compare the time to
 resolution of fever in patients treated with these regimens. VI. Compare the microbiologic
 response by pathogen and site of infection in patients treated with these regimens. VII.
 Compare the percentage of patients whose fever defervesces only after resolution of
 neutropenia (absolute neutrophil count at least 500/mm3) with no therapeutic modification.

 OUTLINE: This is a randomized, double-blind, multicenter study. Patients are stratified
 according to type of malignancy (solid tumor, including lymphoma vs leukemia), prior
 prophylactic antibiotics (yes vs no), and participating center. Patients are randomized to
 one of two treatment arms. Arm I: Patients receive levofloxacin IV over 90 minutes once daily
 for 14-28 days. Arm II: Patients receive cefepime IV over 30 minutes every 8 hours for 14-28
 days. Patients may receive additional antifungal, antibacterial, or antiviral therapy if
 condition has deteriorated, no response is seen in 72 hours, or and infection is suspected or
 documented. Patients are followed at 1-3 and 7-12 days and then at 3-4 weeks.

 PROJECTED ACCRUAL: Approximately 260-400 patients (130-200 per treatment arm) will be accrued
 for this study.
DISEASE CHARACTERISTICS: Diagnosis of malignancy Solid tumor (including lymphoma) or
 leukemia Hospitalized and anticipated to remain hospitalized during study Febrile defined
 as oral temperature of at least 100.4 degrees F (38 degrees C) on 2 occasions within 24
 hours OR at least 100.8 degrees F (38.2 degrees C) on a single reading No obvious
 noninfectious cause of fever (e.g., platelet transfusion) Neutropenic, defined as absolute
 neutrophil count (ANC) currently less than 500/mm3 OR anticipated to be less than 500/mm3
 within 24 hours of study entry Anticipated ANC to be less than 500/mm3 for at least 72
 hours No neutropenia unassociated with malignancy No chronic neutropenia No neutropenia
 anticipated to last more than 14 days No acute myelogenous leukemia unless receiving
 consolidation chemotherapy or induction dose that does not prolong neutropenia for more
 than 3 weeks No infection due to an identified organism No high likelihood of infection due
 to anaerobic organisms, including intra-abdominal infections or perirectal abscess at
 admission No known osteomyelitis No requirement for new antifungal agent

 PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Not specified Life
 expectancy: At least 14 days Hematopoietic: See Disease Characteristics Hepatic: Not
 specified Renal: Creatinine clearance at least 20 mL/min No oliguria (urine output less
 than 20 mL/hour) unresponsive to fluid challenge Cardiovascular: No shock or hypotension
 (supine systolic blood pressure less than 80 mmHg) unresponsive to fluid challenge Other:
 Not pregnant or nursing Negative pregnancy test Fertile patients must use effective
 contraception No HIV infection with CD4 counts less than 200/mm3 No significant risk for
 seizures No unstable psychiatric disorder Weight greater than 40 kg No prior allergic or
 severe adverse reaction to study drugs or to any member of the quinolone or beta-lactam
 class of antibacterials No disorder or disease that would preclude study

 PRIOR CONCURRENT THERAPY: Biologic therapy: No prior sargramostim (GM-CSF) or filgrastim
 (G-CSF) for current course of chemotherapy Concurrent GM-CSF or G-CSF allowed if
 neutropenia lasts at least 3 days Chemotherapy: See Disease Characteristics Endocrine
 therapy: Not specified Radiotherapy: Not specified Surgery: Not specified Other: No prior
 treatment under this protocol No prior prophylactic anti-infectives other than acyclovir or
 sulfamethoxazole with trimethoprim At least 72 hours since prior systemic antibiotics
 (except prophylactic sulfamethoxazole with trimethoprim) At least 30 days since prior
 experimental drug or medical device (except drugs currently marketed in the United States
 for the treatment of the malignancy) No other concurrent systemic antibacterial agents No
 concurrent topical antimicrobial agents