GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN PATIENTS WITH NEUTROPENIC FEVER IS POTENT AFTER LOW-RISK BUT NOT AFTER HIGH-RISK NEUTROPENIC CHEMOTHERAPY REGIMENS - RESULTS OF A RANDOMIZED PHASE-III TRIAL

Purpose: A randomized unblinded phase III trial was designed to determ ine the ability of granulocyte-macrophage colony-stimulating factor (G M-CSF) to accelerate recovery from febrile neutropenia induced by chem otherapy. Patients and Methods: A fetal of 68 patients with febrile ne utropenia following chemotherapy defined as axillary temperature great er than 38 degrees C and absolute neutrophil count (ANC) less than 1 x 10(9)/L were included. After stratification for high- and low-risk ch emo therapy to induce febrile neutropenia, treatment was randomized be tween GM-CSF at 5 mu g/kg/d or control, both being associated with ant ibiotics. Results: GM-CSF significantly reduced the median duration of neutropenia from 6 to 3 days for ANC less than 1 x 10(9)/L (P < .001) and from 4 to 3 days for ANC less than 0.5 x 10(9)/L(P = .024), days of hospitalization required for febrile neutropenia, and duration of a ntibiotics during hospitalization. The greatest benefit with GM-CSF ap peared for patients who had received low-risk chemotherapy, for which the median duration of ANC less than 1 x 10(9)/L. was reduced from 7 t o 2.5 days (P < .001) and from 4 to 2 days for ANC less than 0.5 x 10( 9)/L (P = .0011), the duration of hospitalization during the study fro m 7 to 4 days (P = .003), and the duration on antibiotics during hospi talization from 7 to 3.5 days (P < .001). A multivariate analysis, usi ng Cox regression, showed that variables predictive for recovery from neutropenia were GM-CSF (P = .0010) and time interval between the firs t day of chemotherapy and randomization (P = .030). There was no benef it for GM CSF when high-risk chemotherapy was considered. Conclusion: GM-CSF significantly shortened duration of neutropenia, duration of ne utropenic fever-related hospitalization, and duration on antibiotics d uring hospitalization when febrile neutrapenia occurred after low-risk chemotherapy, but not high-risk chemotherapy. J Clin Oncol 16:2930-29 36, (C) 1998 by American Society of Clinical Oncology.