Randomized phase III trial of dose-dense chemotherapy supported by whole-blood hematopoietic progenitors in better-prognosis small-cell lung cancer.

2.50
Hdl Handle:
http://hdl.handle.net/10541/76492
Title:
Randomized phase III trial of dose-dense chemotherapy supported by whole-blood hematopoietic progenitors in better-prognosis small-cell lung cancer.
Authors:
Lorigan, Paul C ( 0000-0002-8875-2164 ) ; Woll, Penella J; O'Brien, M; Ashcroft, Linda; Sampson, Mark R; Thatcher, Nick
Abstract:
BACKGROUND: Recent dose-intensity studies of small-cell lung cancer (SCLC) have yielded conflicting results. We carried out a phase III randomized trial in patients with better-prognosis SCLC (i.e., prognostic score of 0-1) to investigate whether doubling the dose density of ifosfamide, carboplatin, and etoposide (ICE) chemotherapy with filgrastim and blood-progenitor-cell support improves survival, compared with standard ICE chemotherapy. METHODS: We studied 318 patients with pathologically proven SCLC who were randomly assigned to receive six cycles of ICE chemotherapy with a 4-week (standard arm) or 2-week (dose-dense arm) interval between cycles. Patients in the dose-dense arm received filgrastim subcutaneously daily on days 4 through 14 and had autologous blood collected before cycles 2 through 6, which was returned 24 hours after treatment. Toxicities, including hematologic toxicity and incidence of neutropenic sepsis, were monitored. Survival was calculated by the Kaplan-Meier method. All statistical tests were two-sided. RESULTS: The delivered median dose intensity was 99% (interquartile range = 96%-100%) for the standard arm and 182% (interquartile range = 163%-196%) for the dose-dense arm. After a median follow-up of 14 months, overall response to treatment was observed in 118 (80%) of the 148 evaluable patients in the standard arm and in 129 (88%) of the 147 evaluable patients in the dose-dense arm, a statistically non-significant difference. Median overall survival was 13.9 months (95% confidence interval [CI] = 12.9 to 15.8 months) in the standard arm and 14.4 months (95% CI = 12.7 to 16.0) in the dose-dense arm, and the 2-year survival was 22% (95% CI = 16% to 29%) and 19% (95% CI = 14% to 27%), respectively--neither difference being statistically significant. The median treatment free time was 286 days (95% CI = 229 to 343 days) for the standard arm and 367 days (95% CI = 321 to 413 days) for the dose-dense arm (difference = 81 days; P = .109). Statistically significantly more hematologic toxicity was reported in the dose-dense arm than in the standard arm, but the number of cycles complicated by neutropenic sepsis was statistically significantly higher in the standard arm than in the dose-dense arm (15.3% versus 11.6%, respectively; difference = 3.7%, 95% CI = -4.1% to 11.5%; P = .03). CONCLUSIONS: Dose-dense ICE chemotherapy for SCLC led to shorter treatment duration and less neutropenic sepsis than did standard ICE but did not improve overall survival.
Affiliation:
Weston Park Hospital, Sheffield, UK. paul.lorigan@manchester.ac.uk
Citation:
Randomized phase III trial of dose-dense chemotherapy supported by whole-blood hematopoietic progenitors in better-prognosis small-cell lung cancer. 2005, 97 (9):666-74 J. Natl. Cancer Inst.
Journal:
Journal of the National Cancer Institute
Issue Date:
4-May-2005
URI:
http://hdl.handle.net/10541/76492
DOI:
10.1093/jnci/dji114
PubMed ID:
15870437
Type:
Article
Language:
en
ISSN:
1460-2105
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorLorigan, Paul C-
dc.contributor.authorWoll, Penella J-
dc.contributor.authorO'Brien, M-
dc.contributor.authorAshcroft, Linda-
dc.contributor.authorSampson, Mark R-
dc.contributor.authorThatcher, Nick-
dc.date.accessioned2009-08-06T12:08:20Z-
dc.date.available2009-08-06T12:08:20Z-
dc.date.issued2005-05-04-
dc.identifier.citationRandomized phase III trial of dose-dense chemotherapy supported by whole-blood hematopoietic progenitors in better-prognosis small-cell lung cancer. 2005, 97 (9):666-74 J. Natl. Cancer Inst.en
dc.identifier.issn1460-2105-
dc.identifier.pmid15870437-
dc.identifier.doi10.1093/jnci/dji114-
dc.identifier.urihttp://hdl.handle.net/10541/76492-
dc.description.abstractBACKGROUND: Recent dose-intensity studies of small-cell lung cancer (SCLC) have yielded conflicting results. We carried out a phase III randomized trial in patients with better-prognosis SCLC (i.e., prognostic score of 0-1) to investigate whether doubling the dose density of ifosfamide, carboplatin, and etoposide (ICE) chemotherapy with filgrastim and blood-progenitor-cell support improves survival, compared with standard ICE chemotherapy. METHODS: We studied 318 patients with pathologically proven SCLC who were randomly assigned to receive six cycles of ICE chemotherapy with a 4-week (standard arm) or 2-week (dose-dense arm) interval between cycles. Patients in the dose-dense arm received filgrastim subcutaneously daily on days 4 through 14 and had autologous blood collected before cycles 2 through 6, which was returned 24 hours after treatment. Toxicities, including hematologic toxicity and incidence of neutropenic sepsis, were monitored. Survival was calculated by the Kaplan-Meier method. All statistical tests were two-sided. RESULTS: The delivered median dose intensity was 99% (interquartile range = 96%-100%) for the standard arm and 182% (interquartile range = 163%-196%) for the dose-dense arm. After a median follow-up of 14 months, overall response to treatment was observed in 118 (80%) of the 148 evaluable patients in the standard arm and in 129 (88%) of the 147 evaluable patients in the dose-dense arm, a statistically non-significant difference. Median overall survival was 13.9 months (95% confidence interval [CI] = 12.9 to 15.8 months) in the standard arm and 14.4 months (95% CI = 12.7 to 16.0) in the dose-dense arm, and the 2-year survival was 22% (95% CI = 16% to 29%) and 19% (95% CI = 14% to 27%), respectively--neither difference being statistically significant. The median treatment free time was 286 days (95% CI = 229 to 343 days) for the standard arm and 367 days (95% CI = 321 to 413 days) for the dose-dense arm (difference = 81 days; P = .109). Statistically significantly more hematologic toxicity was reported in the dose-dense arm than in the standard arm, but the number of cycles complicated by neutropenic sepsis was statistically significantly higher in the standard arm than in the dose-dense arm (15.3% versus 11.6%, respectively; difference = 3.7%, 95% CI = -4.1% to 11.5%; P = .03). CONCLUSIONS: Dose-dense ICE chemotherapy for SCLC led to shorter treatment duration and less neutropenic sepsis than did standard ICE but did not improve overall survival.en
dc.language.isoenen
dc.subjectHaematopoietic Stem Cellsen
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.meshDose-Response Relationship, Drug-
dc.subject.meshDrug Administration Schedule-
dc.subject.meshEtoposide-
dc.subject.meshFemale-
dc.subject.meshFilgrastim-
dc.subject.meshHematopoietic Stem Cells-
dc.subject.meshHumans-
dc.subject.meshIfosfamide-
dc.subject.meshIncidence-
dc.subject.meshLung Neoplasms-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshNeutropenia-
dc.subject.meshPrognosis-
dc.subject.meshSeverity of Illness Index-
dc.subject.meshSurvival Analysis-
dc.subject.meshTransplantation, Autologous-
dc.subject.meshTreatment Outcome-
dc.titleRandomized phase III trial of dose-dense chemotherapy supported by whole-blood hematopoietic progenitors in better-prognosis small-cell lung cancer.en
dc.typeArticleen
dc.contributor.departmentWeston Park Hospital, Sheffield, UK. paul.lorigan@manchester.ac.uken
dc.identifier.journalJournal of the National Cancer Instituteen

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