RECOMBINANT HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR ASAN ADJUNCT TO CONVENTIONAL-DOSE IFOSFAMIDE-BASED CHEMOTHERAPY FOR PATIENTS WITH ADVANCED OR RELAPSED GERM-CELL TUMORS - A RANDOMIZED TRIAL

Purpose: Ifosfamide-containing therapy with cisplatin plus either etop oside (VIP) or vinblastine (VeIP) can cure of patients with relapsed g erm cell tumors (GCTs), but results in substantial myelotoxicity. This study sought to assess the impact of recombinant human granulocyte ma crophage colony-stimulating factor (rhGM-CSF) on the severity of neutr openia and incidence of infectious complications in patients who recei ve ifosfamide-based chemotherapy for GCT. Patients and Methods: One hu ndred and four assessable GCT patients from 20 centers were randomized to receive rhGM-CSF with either cycles 1 and 2 or cycles 3 and 4 of c hemotherapy. Standard doses of VIP or VeIP were used. Efficacy data we re analyzed using a parallel design for cycles 1 and 2 before the cros sover. Results: Fewer clinically relevant infections occurred in rhGM- CSF patients (13 of 55, 24%) versus observation patients (22 of 49, 45 %) in cycle 1 (P = .01). Decreases were observed in infections during neutropenia (22% v 43%, P = .03), infections requiring intravenous ant ibiotics (20% v 43%, P = .01), and any infection irrespective of sever ity (29% v 55%, P = .01) in cycle 1. However, there were no significan t differences among the treatment arms in cycle 2 in the proportion of clinically relevant infections (P = .23), infections associated with neutropenia (P = .11), infections requiring antibiotics (P = .22), or any infection (P = .65). rhGM-CSF was discontinued in 14% of cycles be cause of toxicity related to the growth factor. Conclusion: rhGM-CSF r educed the incidence of infections in the first cycle of chemotherapy, but no benefit beyond the initial chemotherapy cycle was evident. Bas ed on the limited clinical impact and the high incidence of rhGM-CSF-r elated toxicity that required growth factor discontinuation, the routi ne administration of rhGM-CSF to prevent neutropenia and infection aft er ifosfamide-based chemotherapy for GCT patients is not recommended.