Journal Article
. 2002 Sep; 20(19):3947-55.
doi: 10.1200/JCO.2002.02.069.

Standard versus intensified chemotherapy with granulocyte colony-stimulating factor support in small-cell lung cancer: a prospective European Organization for Research and Treatment of Cancer-Lung Cancer Group Phase III Trial-08923

Andrea Ardizzoni 1 Vivianne C G Tjan-Heijnen  Pieter E Postmus  Erica Buchholz  Bonne Biesma  Hanna Karnicka-Mlodkowska  Rafal Dziadziuszko  Jos Burghouts  Jan P Van Meerbeeck  Steven Gans  Catherine Legrand  Channa Debruyne  Giuseppe Giaccone  Christian Manegold  European Organization for Research and Treatment of Cancer-Lung Cancer Group  
Affiliations
  • PMID: 12351591
  •     14 citations

Abstract

Purpose: To assess the impact on survival of increasing dose-intensity (DI) of cyclophosphamide, doxorubicin, and etoposide (CDE) in small-cell lung cancer (SCLC).

Patients And Methods: Previously untreated SCLC patients were randomized to standard CDE (cyclophosphamide 1,000 mg/m(2) and doxorubicin 45 mg/m(2) on day 1, and etoposide 100 mg/m(2) on days 1 to 3 every 3 weeks, for five cycles) or intensified CDE (cyclophosphamide 1,250 mg/m(2) and doxorubicin 55 mg/m(2) on day 1, and etoposide 125 mg/m(2) on days 1 to 3 with granulocyte colony-stimulating factor [G-CSF] 5 micro g/kg/d on days 4 to 13 every 2 weeks, for four cycles). Projected cumulative dose was almost identical on the two arms, whereas projected DI was nearly 90% higher on the intensified arm. Two hundred forty-four patients were enrolled. The first 163 patients were also randomized (2 x 2 factorial design) to prophylactic antibiotics or placebo to assess their impact on preventing febrile leukopenia (FL). This report focuses on chemotherapy DI results.

Results: With a median follow-up of 54 months, 216 deaths have occurred. Actually delivered DI on the intensified arm was 70% higher than on the standard arm. Intensified CDE was associated with more grade 4 leukopenia (79% v 50%), grade 4 thrombocytopenia (44% v 11%), anorexia, nausea, and mucositis. FL and number of toxic deaths were similar on the two arms. The objective response rate was 79% for the standard arm and 84% for the intensified arm (P =.315). Median survival was 54 weeks and 52 weeks, and the 2-year survival rates were 15% and 18%, respectively (P =.885).

Conclusion: A 70% increase of CDE actual DI does not translate into an improved outcome in SCLC patients.

Treatment options for small cell lung cancer.
Todd Wolf, Heidi H Gillenwater.
Curr Oncol Rep, 2004 May 27; 6(4). PMID: 15161577
Review.
Management of small cell lung cancer.
Kristen Keon Ciombor, Caio Max S Rocha Lima.
Curr Treat Options Oncol, 2005 Dec 14; 7(1). PMID: 16343369
Review.
Epirubicin/paclitaxel/etoposide in extensive-stage small-cell lung cancer: a phase I-II study.
C Tibaldi, T Prochilo, +7 authors, E Baldini.
Br J Cancer, 2006 Apr 20; 94(9). PMID: 16622468    Free PMC article.
Achieving full-dose, on-schedule administration of ACE chemotherapy every 14 days for the treatment of patients with extensive small-cell lung cancer.
R Pirker, E Ulsperger, +5 authors, T Skacel.
Lung, 2007 Jan 20; 184(5). PMID: 17235728
Modern management of small-cell lung cancer.
Roberta Ferraldeschi, Sofia Baka, +3 authors, Paul Lorigan.
Drugs, 2007 Oct 12; 67(15). PMID: 17927281
Review.
Progress and problems in the application of focused ultrasound for blood-brain barrier disruption.
Natalia Vykhodtseva, Nathan McDannold, Kullervo Hynynen.
Ultrasonics, 2008 May 31; 48(4). PMID: 18511095    Free PMC article.
Review.
Phase III randomised trial of doxorubicin-based chemotherapy compared with platinum-based chemotherapy in small-cell lung cancer.
S Baka, R Califano, +6 authors, P Lorigan.
Br J Cancer, 2008 Jul 31; 99(3). PMID: 18665190    Free PMC article.
Extensive disease small cell lung cancer dose-response relationships: implications for resistance mechanisms.
David J Stewart, Constance Johnson, +3 authors, B Nebiyou Bekele.
J Thorac Oncol, 2010 Oct 01; 5(11). PMID: 20881640    Free PMC article.
Accelerated BEP: a phase I trial of dose-dense BEP for intermediate and poor prognosis metastatic germ cell tumour.
Y Rimmer, J Chester, +9 authors, M V Williams.
Br J Cancer, 2011 Aug 19; 105(6). PMID: 21847130    Free PMC article.
A way forward on the medically appropriate use of white cell growth factors.
Thomas J Smith, Bruce E Hillner.
J Clin Oncol, 2012 Mar 01; 30(14). PMID: 22370327    Free PMC article.
Review.
SEOM clinical guidelines for the treatment of small-cell lung cancer 2013.
M Dómine Gómez, T Morán Bueno, +3 authors, SEOM.
Clin Transl Oncol, 2013 Sep 06; 15(12). PMID: 24005836
Review.
Chemotherapy for small cell lung cancer: a comprehensive review.
Syed Mustafa Karim, Jamal Zekri.
Oncol Rev, 2012 Mar 05; 6(1). PMID: 25992206    Free PMC article.
Review.
Targeting angiogenesis in small cell lung cancer.
Michalis Stratigos, Alexios Matikas, +2 authors, Vassilis Georgoulias.
Transl Lung Cancer Res, 2016 Sep 22; 5(4). PMID: 27652203    Free PMC article.
Review.
Interventions for preventing oral mucositis for patients with cancer receiving treatment.
Helen V Worthington, Jan E Clarkson, +6 authors, Tasneem Khalid.
Cochrane Database Syst Rev, 2011 Apr 15; (4). PMID: 21491378    Free PMC article.
Systematic Review.