A Phase I/II Study of Dose and Administration of Non-Glycosylated Bacterially Synthesized G-M CSF in Chemotherapy-Induced Neutropenia in Patients with Non-Hodgkin's Lymphomas

Recombinant human granulocyte-marcrophage colony-stimulating factor (rhGM-CSF) derived from E. coli was administered to 24 previously untreated patients with non-Hodgkin's lymphoma following the first cycle of CHOP chemotherapy. Four dose levels were examined, 1.5, 3.0, 5.5 and 11 μg/kg and patients were randomized to receive the drug either once or twice daily subcutaneously (s.c). During rhGM-CSF treatment, the leucocyte counts increased up to 3-4 fold in 20/24 patients, reaching a peak 24-48 (mean 35) hours after initiation of rhGM-CSF. The leucopenic period in cycle one of the CHOP chemotherapy with rhGM-CSF, was shorter than after the course of chemotherapy without rhGM-CSF and also shorter when compared to cycle one of CHOP in the 127 historical controls (p < 0.05 and p < 0.001 respectively). Similar results were observed for neutrophil counts.No effect was seen on platelet counts at nadir but a significant, although moderate increase occurred in the recovery period on days 15 and 22 when compared to control cycles and historical controls. When dose levels were compared, there was only a trend to higher WBC counts at the higher dose groups (5.5 and 11 μg/kg) when compared to the two lower dose groups (1.5 and 3.0 μg/kg).In the overall evaluation there was no statistical significant difference in results between patients treated s.c. once daily versus twice daily. However when only the two highest dose levels (5.5 + 11 μg/kg) were compared, s.c. administration of rhGM-CSF twice daily led to higher leucocyte counts than once daily in the recovery period on day 15 (p < 0.05).Side effects were mild and transient comprising lowgrade fever, flu-like symptoms, chest/bone pain and erythema at the site of injection. There was no evidence of stimulation of tumor growth. In conclusion E. coli derived human rhGM-CSF was well tolerated and able to alleviate the granulocytopenic period (and to some degree the thrombocytopenia) following standard chemotherapy in patients with non-Hodgkin's lymphoma.