title: Chemoradiotherapy with or without granulocyte-macrophage colony-stimulating factor in the treatment of limited-stage small-cell lung cancer: a prospective phase III randomized study of the Southwest Oncology Group.
abstract: OBJECTIVE
  This phase III randomized trial was designed to determine if granulocyte-macrophage colony-stimulating factor (GM-CSF) reduces the hematologic toxicity and morbidity induced by chemoradiotherapy in limited-stage small-cell lung cancer (SCLC).
  
  
  METHODS
  This multicenter prospective trial randomized 230 patients to receive chemotherapy and radiotherapy (RT) with or without GM-CSF given on days 4 to 18 of each of six cycles. The primary end point was hematologic toxicity. Secondary end points included the following: nonhematologic toxicities; days of (1) fever, (2) antibiotics, (3) hospitalization, and (4) infection; number of transfusions; drug doses delivered; and response rates and survival.
  
  
  RESULTS
  There was a statistically significant increase in the frequency and duration of life-threatening thrombocytopenia (P < .001) in patients randomized to GM-CSF. GM-CSF patients had significantly more toxic deaths (P < .01), more nonhematologic toxicities, more days in hospital, a higher incidence of intravenous (IV) antibiotic usage, and more transfusions. Patients randomized to GM-CSF had higher WBC and neutrophil nadirs (P < .01), but no significant difference in the frequency of grade 4 leukopenia or neutropenia. Patients randomized to GM-CSF had a lower complete response rate (36% v 44%), but the differences were not significant (P = .29). There were no significant differences in survival (median, 14 months on GM-CSF and 17 months on no GM-CSF; P = .15).
  
  
  CONCLUSIONS
  GM-CSF, as delivered in this study, should not be included with concurrent chemoradiotherapy treatment programs for limited-stage SCLC. The simultaneous use of hematopoietic colony-stimulating factors (CSFs) and chemoradiotherapy should be performed only in experimental settings. Chemoradiotherapy programs with cisplatin and etoposide ([VP-16] PE) and simultaneous chest RT produce grade 4 neutropenia and thrombocytopenia in a small-enough proportion of patients that prophylactic hematopoietic growth factors are clinically unnecessary.
authors.affiliation: Division of Medical Oncology, University of Colorado, Denver, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Bunn
authors.forename: J
authors.initials: J
authors.lastname: Crowley
authors.forename: K
authors.initials: K
authors.lastname: Kelly
authors.forename: M B
authors.initials: MB
authors.lastname: Hazuka
authors.forename: K
authors.initials: K
authors.lastname: Beasley
authors.forename: C
authors.initials: C
authors.lastname: Upchurch
authors.forename: R
authors.initials: R
authors.lastname: Livingston
authors.forename: G R
authors.initials: GR
authors.lastname: Weiss
authors.forename: W J
authors.initials: WJ
authors.lastname: Hicks
authors.forename: D R
authors.initials: DR
authors.lastname: Gandara
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007970:Leukopenia / Q000209:etiology / Q000517:prevention & control; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000209:etiology / Q000517:prevention & control*; D011446:Prospective Studies; D013921:Thrombocytopenia / Q000209:etiology / Q000517:prevention & control*
chemical_list: D000900:Anti-Bacterial Agents; D005047:Etoposide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002945:Cisplatin