A threefold dose intensity treatment with ifosfamide, carboplatin, and etoposide for patients with small cell lung cancer: A randomized trial

Serge Leyvraz, Sandro Pampallona, Giovanni Martinelli, Ferdinand Ploner, Lucien Perey, Savina Aversa, Solange Peters, Paal Brunsvig, Ana Montes, Andrzej Lange, Ugur Yilmaz, Giovanni Rosti

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Abstract

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.

Original languageEnglish
Pages (from-to)533-541
Number of pages9
JournalJournal of the National Cancer Institute
Volume100
Issue number8
DOIs
Publication statusPublished - 2008

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Leyvraz, S., Pampallona, S., Martinelli, G., Ploner, F., Perey, L., Aversa, S., Peters, S., Brunsvig, P., Montes, A., Lange, A., Yilmaz, U., & Rosti, G. (2008). A threefold dose intensity treatment with ifosfamide, carboplatin, and etoposide for patients with small cell lung cancer: A randomized trial. Journal of the National Cancer Institute, 100(8), 533-541. https://doi.org/10.1093/jnci/djn088