title: Phase I trial of etoposide, carboplatin, and GM-CSF in extensive small-cell lung cancer: a Cancer and Leukemia Group B study (CALGB 8832).
abstract: The maximum tolerated dose (MTD) of etoposide and carboplatin without growth factor support was previously defined by Cancer and Leukemia Group B (CALGB) as 200 and 125 mg/m2/day x 3, respectively, given every 28 days to previously untreated patients who have extensive, small-cell lung cancer (SCLC). Myelosuppression was dose-limiting. The purpose of this phase I trial was to determine if granulocyte macrophage colony-stimulating factor (GM-CSF) support allows the dosage of the combination of etoposide and carboplatin to be increased above the previously determined MTD. In this CALGB study of 44 evaluable patients with performance status 0-2, cohorts were treated with etoposide and carboplatin given intravenously on days 1-3 followed by GM-CSF (molgramostim) given subcutaneously on days 4-18. Four dose levels of bacteria-derived recombinant GM-CSF (5, 10, 20 microg/kg/day and 5 microg/kg every 12 h), three dose levels of etoposide (200, 250, and 300 mg/m2/day x 3), and two dose levels of carboplatin (125 and 150 mg/m2/day x 3) were evaluated. There was no chemotherapy dose escalation in individual patients. With 5 microg/kg/d GM-CSF, the first etoposide and carboplatin cycle of 300 and 150 mg/m2/day x 3, respectively, could be administered with acceptable toxicity. However, GM-CSF did not allow repeated administration of this dose-escalated regimen every 21 days, since delayed platelet and/or neutrophil recovery was dose limiting in later cycles. These results demonstrate that GM-CSF alone has limited capability to support the repeated administration of high doses of etoposide and carboplatin. CALGB currently is testing the ability of interleukin (IL)-6 given with GM-CSF to ameliorate the cumulative myelosuppression of this intense regimen.
authors.affiliation: Veterans Administration Medical Center and the University of Minnesota Medical Center, Minneapolis 55417, USA.
authors.forename: S D
authors.initials: SD
authors.lastname: Luikart
authors.forename: J E
authors.initials: JE
authors.lastname: Herndon
authors.forename: D R
authors.initials: DR
authors.lastname: Hollis
authors.forename: M
authors.initials: M
authors.lastname: MacDonald
authors.forename: L H
authors.initials: LH
authors.lastname: Maurer
authors.forename: J
authors.initials: J
authors.lastname: Crawford
authors.forename: G H
authors.initials: GH
authors.lastname: Clamon
authors.forename: J
authors.initials: J
authors.lastname: Wright
authors.forename: M C
authors.initials: MC
authors.lastname: Perry
authors.forename: H
authors.initials: H
authors.lastname: Ozer
authors.forename: M R
authors.initials: MR
authors.lastname: Green
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000556:secondary; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D016019:Survival Analysis
chemical_list: D005047:Etoposide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016190:Carboplatin