title: Prospective randomized comparison of morning versus night daily single subcutaneous administration of granulocyte-macrophage-colony stimulating factor in patients with soft tissue or bone sarcoma.
abstract: BACKGROUND
  Hematopoietic growth factors (HGFs) have been used to reduce the neutropenic complications of cytotoxic chemotherapy so that higher doses may be given. The authors have previously shown that endogenous serum granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage-colony stimulating factor (GM-CSF) levels at night (p.m.) were significantly higher than those in the morning (a.m.).
  
  
  METHODS
  Twenty-four patients with soft tissue or bone sarcoma who were treated with high dose ifosfamide-based chemotherapy were enrolled in this study. Patients were randomized to either a.m. or p.m. treatment. GM-CSF was administered at a dose of 5 microg/kg/day at 10 a.m. or 10 p.m., beginning 36-48 hours after the last chemotherapy dose. GM-CSF therapy was continued until the neutrophil count exceeded 1,000/mm3 for 2 consecutive days. Leukocyte, neutrophil, monocyte, and platelet counts were measured immediately before GM-CSF administration and exactly 12 hours after the first dose of GM-CSF, and every 24 hours until 3 days after the cessation of GM-CSF.
  
  
  RESULTS
  The mean duration of Grade 3-4 neutropenia was 5.3 +/- 0.4 days for the a.m. treatment arm and 6.5 +/- 0.3 days for the p.m. treatment arm (P = 0.017). Although the duration of neutropenia in the a.m. arm was significantly shorter than in the p.m. arm, there were no differences related to the number of febrile neutropenic episodes or the duration of antibiotic administration. Also, there were no differences in the side effects observed in the a.m. and p.m. arms.
  
  
  CONCLUSIONS
  The finding of 1.2 days' difference in the duration of Grade 3-4 neutropenia warrants further study of chronotherapy with HGFs.
authors.affiliation: Department of Medical Oncology, Ankara University, Turkey.
authors.forename: D
authors.initials: D
authors.lastname: Dinçol
authors.forename: M
authors.initials: M
authors.lastname: Samur
authors.forename: A
authors.initials: A
authors.lastname: Pamir
authors.forename: O
authors.initials: O
authors.lastname: Sencan
authors.forename: H
authors.initials: H
authors.lastname: Akbulut
authors.forename: B
authors.initials: B
authors.lastname: Yalçin
authors.forename: H
authors.initials: H
authors.lastname: Onur
authors.forename: A
authors.initials: A
authors.lastname: Demirkazik
authors.forename: F C
authors.initials: FC
authors.lastname: Senler
authors.forename: F
authors.initials: F
authors.lastname: Içli
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy*; D016009:Chi-Square Distribution; D019454:Chronotherapy; D005260:Female; D005334:Fever / Q000517:prevention & control; D005500:Follow-Up Studies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D007069:Ifosfamide / Q000009:adverse effects / Q000627:therapeutic use; D007279:Injections, Subcutaneous; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D009000:Monocytes / Q000187:drug effects; D009503:Neutropenia / Q000517:prevention & control; D009504:Neutrophils / Q000187:drug effects; D010976:Platelet Count / Q000187:drug effects; D011446:Prospective Studies; D012509:Sarcoma / Q000188:drug therapy*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy*; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D018906:Antineoplastic Agents, Alkylating; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007069:Ifosfamide