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.

2.50
Hdl Handle:
http://hdl.handle.net/10541/91693
Title:
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.
Authors:
Steward, William P; Von Pawel, J; Gatzemeier, U; Woll, Penella J; Thatcher, Nick; Koschel, G; Clancy, L; Verweij, Jaap; De Wit, Ronald; Pfeifer, W; Fennelly, J; Von Eiff, M; Frisch, J
Abstract:
PURPOSE: 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.
Affiliation:
Department of Oncology, Leicester Royal Infirmary, United Kingdom. william.steward@uni.romp.msmail.lri-tr.trent.nhs.uk
Citation:
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. 1998, 16 (2):642-50 J. Clin. Oncol.
Journal:
Journal of Clinical Oncology
Issue Date:
Feb-1998
URI:
http://hdl.handle.net/10541/91693
PubMed ID:
9469353
Type:
Article
Language:
en
ISSN:
0732-183X
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorSteward, William Pen
dc.contributor.authorVon Pawel, Jen
dc.contributor.authorGatzemeier, Uen
dc.contributor.authorWoll, Penella Jen
dc.contributor.authorThatcher, Nicken
dc.contributor.authorKoschel, Gen
dc.contributor.authorClancy, Len
dc.contributor.authorVerweij, Jaapen
dc.contributor.authorDe Wit, Ronalden
dc.contributor.authorPfeifer, Wen
dc.contributor.authorFennelly, Jen
dc.contributor.authorVon Eiff, Men
dc.contributor.authorFrisch, Jen
dc.date.accessioned2010-02-09T17:11:33Z-
dc.date.available2010-02-09T17:11:33Z-
dc.date.issued1998-02-
dc.identifier.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.en
dc.identifier.issn0732-183X-
dc.identifier.pmid9469353-
dc.identifier.urihttp://hdl.handle.net/10541/91693-
dc.description.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.en
dc.language.isoenen
dc.subjectLung Canceren
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols-
dc.subject.meshCarboplatin-
dc.subject.meshCarcinoma, Small Cell-
dc.subject.meshDouble-Blind Method-
dc.subject.meshEtoposide-
dc.subject.meshFemale-
dc.subject.meshGranulocyte-Macrophage Colony-Stimulating Factor-
dc.subject.meshHumans-
dc.subject.meshIfosfamide-
dc.subject.meshLung Neoplasms-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshProspective Studies-
dc.subject.meshSurvival Rate-
dc.subject.meshVincristine-
dc.titleEffects 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.en
dc.typeArticleen
dc.contributor.departmentDepartment of Oncology, Leicester Royal Infirmary, United Kingdom. william.steward@uni.romp.msmail.lri-tr.trent.nhs.uken
dc.identifier.journalJournal of Clinical Oncologyen

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