title: Received dose-intensity: a randomized trial of weekly chemotherapy with and without granulocyte colony-stimulating factor in small-cell lung cancer.
abstract: OBJECTIVE
  A prospective randomized trial to determine if granulocyte colony-stimulating factor (G-CSF) could increase the received dose-intensity (RDI) of weekly chemotherapy in patients with small-cell lung cancer (SCLC).
  
  
  METHODS
  Forty patients with SCLC with good prognostic features (all patients with limited disease [LD], and extensive-disease [ED] patients with Eastern Cooperative Oncology Group [ECOG] 0 or 1 and plasma alkaline phosphatase levels < 1.5 times the upper limit of normal) were randomized to receive weekly chemotherapy with or without G-CSF. G-CSF (5 micrograms/kg) was self-administered subcutaneously on days when chemotherapy was not given. Chemotherapy consisted of cisplatin 50 mg/m2 intravenously (IV) on day 1 and etoposide 75 mg/m2 IV on days 1 and 2 alternating weekly with ifosfamide 2 g/m2 IV (with mesna) and doxorubicin 25 mg/m2 on day 1, for a total of 12 courses. Dose modifications (dose reductions and treatment delays) were made according to defined hematologic criteria.
  
  
  RESULTS
  Dose reductions were made at some point during treatment in 12 of 17 patients in the control arm and in 11 of 23 patients in the G-CSF arm (P = .20). The proportion of patients experiencing dose reductions due to leukopenia was significantly higher in the control arm (nine of 17) compared with the G-CSF arm (four of 23, P < .04). Cycle delays due to leukopenia were similar in both arms of the study. The RDI was 82% of projected in the control arm (95% confidence interval [CI], 79% to 84%) and 84% in patients receiving G-CSF (95% CI, 82% to 87%) (P value not significant).
  
  
  CONCLUSIONS
  In this randomized trial, G-CSF significantly decreased dose reductions due to neutropenia. However, administration of G-CSF did not decrease dose reductions or treatment delays to a level that would allow an increase in received dose-intensity. Nonhematologic toxicities such as increased creatinine concentration also prevented an increase in the RDI in the G-CSF arm.
authors.affiliation: Guy's Hospital, Medical Oncology Clinic, London, England.
authors.forename: D W
authors.initials: DW
authors.lastname: Miles
authors.forename: O
authors.initials: O
authors.lastname: Fogarty
authors.forename: C M
authors.initials: CM
authors.lastname: Ash
authors.forename: R M
authors.initials: RM
authors.lastname: Rudd
authors.forename: C W
authors.initials: CW
authors.lastname: Trask
authors.forename: S G
authors.initials: SG
authors.lastname: Spiro
authors.forename: W M
authors.initials: WM
authors.lastname: Gregory
authors.forename: J A
authors.initials: JA
authors.lastname: Ledermann
authors.forename: R L
authors.initials: RL
authors.lastname: Souhami
authors.forename: P G
authors.initials: PG
authors.lastname: Harper
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000517:prevention & control*; D018288:Carcinoma, Small Cell / Q000188:drug therapy*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D016179:Granulocyte Colony-Stimulating Factor