Effects of granulocyte-macrophage colony-stimulating factor and dose intensification of V-ICE chemotherapy in small-cell lung cancer: a prospective randomized study of 300 patients.
AuthorsSteward, William P
Von Pawel, J
Woll, Penella J
De Wit, Ronald
Von Eiff, M
AffiliationDepartment of Oncology, Leicester Royal Infirmary, United Kingdom. email@example.com
MetadataShow full item record
AbstractPURPOSE: To assess whether granulocyte-macrophage colony-stimulating factor (GM-CSF) reduces the toxicity of chemotherapy and alters delivered dose-intensity. To assess the feasibility of dose-intensification of chemotherapy in small-cell lung cancer (SCLC) and determine whether it has an impact on outcome. MATERIALS AND METHODS: Patients with good- or intermediate-prognosis SCLC entered a prospective multicenter study that involved a 2 x 2 factorial design with randomization to six cycles of chemotherapy with ifosfamide 5 g/m2, carboplatin 300 mg/m2, etoposide 120 mg/m2 intravenously (I.V.) on days 1 and 2 and 240 mg/m2 orally on day 3, and vincristine 0.5 mg/m2 I.V. on day 15 (V-ICE) every 3 weeks (intensified arm) or every 4 weeks (standard arm). A second double-blind randomization to subcutaneous GM-CSF (250 microg/m2/d) or placebo for 14 days between chemotherapy cycles was made. RESULTS: Three hundred patients were entered. Myelosuppression was the main toxicity, with no significant difference in the incidence or grade between treatment groups. The incidence of febrile neutropenia and bacteriologically confirmed sepsis was unaffected by chemotherapy schedule or use of GM-CSF. Twenty-six percent greater dose-intensity was delivered in the intensified arm, with a trend for greater dose-intensity for those who received GM-CSF. Eighty-three percent of patients achieved a response (51% complete response [CR] rate), with no significant difference in response rates between treatment groups. Survival was significantly increased in the intensified compared with the standard arm (P = .0014); median survival rates were 443 versus 351 days and 2-year survival rates were 33% versus 18%, respectively. CONCLUSION: GM-CSF does not reduce the incidence of complications from myelosuppression of aggressive chemotherapy. Dose intensification of V-ICE to a 3-week schedule in SCLC is not associated with increased toxicity, but appears to improve survival significantly. Future studies should aim to deliver chemotherapy in maximal-tolerated dose-intensities.
CitationEffects of granulocyte-macrophage colony-stimulating factor and dose intensification of V-ICE chemotherapy in small-cell lung cancer: a prospective randomized study of 300 patients. 1998, 16 (2):642-50 J. Clin. Oncol.
JournalJournal of Clinical Oncology
- Can cytotoxic dose-intensity be increased by using granulocyte colony-stimulating factor? A randomized controlled trial of lenograstim in small-cell lung cancer.
- Authors: Woll PJ, Hodgetts J, Lomax L, Bildet F, Cour-Chabernaud V, Thatcher N
- Issue date: 1995 Mar
- Ifosfamide, carboplatin, and etoposide plus granulocyte-macrophage colony-stimulating factor: a phase I study with apparent activity in non-small-cell lung cancer.
- Authors: Krigel RL, Palackdharry CS, Padavic K, Haas N, Kilpatrick D, Langer C, Comis R
- Issue date: 1994 Jun
- Phase II study of ifosfamide, carboplatin, etoposide and GM-CSF in small cell lung cancer.
- Authors: Thongprasert S
- Issue date: 2000 May
- A threefold dose intensity treatment with ifosfamide, carboplatin, and etoposide for patients with small cell lung cancer: a randomized trial.
- Authors: Leyvraz S, Pampallona S, Martinelli G, Ploner F, Perey L, Aversa S, Peters S, Brunsvig P, Montes A, Lange A, Yilmaz U, Rosti G, Solid Tumors Working Party of the European Group for Blood and Marrow Transplantation.
- Issue date: 2008 Apr 16
- Dose-intense therapy with etoposide, ifosfamide, cisplatin, and epirubicin (VIP-E) in 100 consecutive patients with limited- and extensive-disease small-cell lung cancer.
- Authors: Fetscher S, Brugger W, Engelhardt R, Kanz L, Hasse J, Frommhold H, Wenger M, Lange W, Mertelsmann R
- Issue date: 1997 Jan