IMPROVING TREATMENT OF CHEMOTHERAPY-INDUCED NEUTROPENIC FEVER BY ADMINISTRATION OF COLONY-STIMULATING FACTORS

Background: Several randomized trials have tested the use of granulocy te colony-stimulating factor (G-CSF) and granulocyte-macrophage colony -stimulating factor (GMCSF) in relieving chemotherapy-induced bone mar row suppression. However, the use of CSFs in the treatment of neutrope nic fever remains virtually unexplored. Purpose: This study evaluated the benefits of adding CSF therapy to the standard antibiotic treatmen ts given to cancer patients for chemotherapy-induced neutropenic fever . The usefulness of CSFs was quantified in terms of reducing the follo wing: (a) the duration of neutropenia, (b) the length of hospitalizati on, and (c) the overall cost of the treatment. Methods: A randomized t rial was conducted to test whether the administration of either G-CSF or GM-CSF improved the outcome of standard antibiotic therapy (ceftazi dime plus amikacin) in nonleukemic cancer patients with fever (>38 deg rees C) and grade IV neutropenia (absolute neutrophil count [ANC] <500 /mm(3)) induced by standard-dose chemotherapy. Of 121 patients who ent ered the trial, 39 received G-CSF (5 mu g/kg body weight per day), 39 received GM-CSF (5 mu g/kg body weight per day), and 43 received a pla cebo beginning just after the first dose of antibiotics. Treatments we re continued for at least 5 days (7 days with clinically or microbiolo gically documented infections) or until 2 days after fever subsided an d ANCs rose above 1000/mm(3). Results: The median duration of grade IV neutropenia (ANC of <500/mm(3)) was 2 days in both CSF arms and 3 day s in the placebo arm (P<.001). The median duration of neutropenia with an ANC of less than 1000/mm(3) was also significantly shorter in pati ents receiving G-CSF or GM-CSF (P<.001). The median duration of fever was similar in the three arms. The median hospital stay was 5 days (ra nge, 5-14 days) in the G-CSF arm, 5 days (range, 5-10 days) in the GM- CSF arm, and 7 days (range, 5-34 days) in the placebo arm (P<.001). Th e median time on CSF was 4 days in both treatment arms. The mean cost of overall treatment was reduced by $1300-$1400 in the CSF arms compar ed with the placebo arm (P =.11 for G-CSF versus placebo; P =.06 for G M-CSF versus placebo; P =.7 for G-CSF versus GM-CSF). Conclusions: Add ing G-CSF or GMCSF therapy to antibiotic treatment shortens the durati on of neutropenia and the duration of hospitalization in patients with neutropenic fever. A statistically nonsignificant trend toward lower cost was observed in the CSF arms as compared with the placebo arm. Im plications: The benefits of CSFs to cancer patients with chemotherapy- induced neutropenic fever merit further evaluation in large randomized trials.