Journal of the National Cancer Institute Advance Access published online on April 8, 2008
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djn088
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© The Author 2008. Published by Oxford University Press.
ARTICLES |
A Threefold Dose Intensity Treatment With Ifosfamide, Carboplatin, and Etoposide for Patients With Small Cell Lung Cancer: A Randomized Trial
On behalf of the Solid Tumors Working Party of the European Group for Blood and Marrow Transplantation
Affiliations of authors: Centre Pluridisciplinaire d'Oncologie, University Hospital, Lausanne, Switzerland (SL, LP, S. Peters); ForMed, Evolène, Switzerland (S. Pampallona); Insituto Europeo di Oncologia, Milano, Italy (GM); Medical University, Graz, Austria (FP); Azienda Ospedaliera di Padova, Padova, Italy (SA); The Norwegian Radium Hospital, Oslo, Norway (PB); Institute Catalan of Oncology, Barcelona, Spain, (AM); L. Hirszfeld Institute of Immunology and Experimental Hematology, Wroclaw, Poland (AL); Dokuz Eylül Universitesi, Izmir, Turkey (UY); Ospedale Ca' Foncello, Treviso, Italy (GR)
Correspondence to: Serge Leyvraz, MD, Centre Pluridisciplinaire d'Oncologie, University Hospital, Rue du Bugnon 46, 1011 Lausanne, Switzerland (e-mail: serge.leyvraz{at}chuv.ch).
Background: The dose intensity of chemotherapy can be increased to the highest possible level by early administration of multiple and sequential high-dose cycles supported by transfusion with peripheral blood progenitor cells (PBPCs). A randomized trial was performed to test the impact of such dose intensification on the long-term survival of patients with small cell lung cancer (SCLC).
Methods: Patients who had limited or extensive SCLC with no more than two metastatic sites were randomly assigned to high-dose (High, n = 69) or standard-dose (Std, n = 71) chemotherapy with ifosfamide, carboplatin, and etoposide (ICE). High-ICE cycles were supported by transfusion with PBPCs that were collected after two cycles of treatment with epidoxorubicin at 150 mg/m2, paclitaxel at 175 mg/m2, and filgrastim. The primary outcome was 3-year survival. Comparisons between response rates and toxic effects within subgroups (limited or extensive disease, liver metastases or no liver metastases, Eastern Cooperative Oncology Group performance status of 0 or 1, normal or abnormal lactate dehydrogenase levels) were also performed.
Results: Median relative dose intensity in the High-ICE arm was 293% (range = 174%–392%) of that in the Std-ICE arm. The 3-year survival rates were 18% (95% confidence interval [CI] = 10% to 29%) and 19% (95% CI = 11% to 30%) in the High-ICE and Std-ICE arms, respectively. No differences were observed between the High-ICE and Std-ICE arms in overall response (n = 54 [78%, 95% CI = 67% to 87%] and n = 48 [68%, 95% CI = 55% to 78%], respectively) or complete response (n = 27 [39%, 95% CI = 28% to 52%] and n = 24 [34%, 95% CI = 23% to 46%], respectively). Subgroup analyses showed no benefit for any outcome from High-ICE treatment. Hematologic toxicity was substantial in the Std-ICE arm (grade 
3 neutropenia, n = 49 [70%]; anemia, n = 17 [25%]; thrombopenia, n = 17 [25%]), and three patients (4%) died from toxicity. High-ICE treatment was predictably associated with severe myelosuppression, and five patients (8%) died from toxicity.
Conclusions: The long-term outcome of SCLC was not improved by raising the dose intensity of ICE chemotherapy by threefold.
| CONTEXT AND CAVEATS Prior knowledge Most small cell lung cancers (SCLCs) recur and become resistant to chemotherapy. Study design Randomized trial to compare high-dose (High) with standard-dose (Std) ifosfamide, carboplatin, and etoposide (ICE) in SCLC patients with limited or extensive disease. Contributions The treatment intensity in the High-ICE arm was almost three times that in the Std-ICE arm. No differences between the two groups in 3-year survival or in overall or complete response were observed. Both treatments induced severe toxicities. Implications Long-term outcome of SCLC was not improved by increasing ICE treatment intensity nearly threefold, and toxicities were severe. Thus, intense ICE therapy for SCLC should not be used in the future. Limitations The study had low accrual, and the initial trial design had to be altered to include interim analyses.
|
Manuscript received October 2, 2007; revised January 25, 2008; accepted February 27, 2008.
Editorial about this Article
Related Article in JNCI
CiteULike 
Connotea 
Del.icio.us What's this?
J Natl Cancer Inst 2008 100: 520-521.
J Natl Cancer Inst 2008 100: 519.
This article has been cited by other articles:
|
|
 |
|
  M. Bregni and P. Pedrazzoli Re: 'A Threefold Dose Intensity Treatment With Ifosfamide, Carboplatin, and Etoposide for Patients With Small-Cell Lung Cancer: A Randomized Trial' J Natl Cancer Inst, January 7, 2009; 101(1): 67 - 67. [Full Text] [PDF]
|
|
|
|
|
|
P. A. Bunn Jr Diseases Desperate Grown J Natl Cancer Inst, April 16, 2008; 100(8): 520 - 521. [Full Text] [PDF]
|
|