title: 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.
abstract: Recombinant human granulocyte-macrophage 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 micrograms/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 leukopenic 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 micrograms/kg) when compared to the two lower dose groups (1.5 and 3.0 micrograms/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 micrograms/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).(ABSTRACT TRUNCATED AT 250 WORDS)
authors: Department of Hematology, University Hospital Rigshospitalet, Copenhagen, Denmark.
authors: D
authors: D
authors: Hovgaard
authors: N I
authors: NI
authors: Nissen
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use / Q000633:toxicity*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000628:therapy*; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011994:Recombinant Proteins / Q000627:therapeutic use / Q000633:toxicity; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D011994:Recombinant Proteins; D014750:Vincristine; D004317:Doxorubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide; D011241:Prednisone