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

Research output: Contribution to journalArticle

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

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Ifosfamide
Carboplatin
Small Cell Lung Carcinoma
Etoposide
Confidence Intervals
Therapeutics
Drug Therapy
Blood Cells
Stem Cells
Neoplasm Metastasis
Survival
Poisons
Paclitaxel
Neutropenia
L-Lactate Dehydrogenase
Thrombocytopenia
Liver Diseases
Anemia
Survival Rate

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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A threefold dose intensity treatment with ifosfamide, carboplatin, and etoposide for patients with small cell lung cancer : A randomized trial. / Leyvraz, Serge; Pampallona, Sandro; Martinelli, Giovanni; Ploner, Ferdinand; Perey, Lucien; Aversa, Savina; Peters, Solange; Brunsvig, Paal; Montes, Ana; Lange, Andrzej; Yilmaz, Ugur; Rosti, Giovanni.

In: Journal of the National Cancer Institute, Vol. 100, No. 8, 2008, p. 533-541.

Research output: Contribution to journalArticle

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, vol. 100, no. 8, pp. 533-541. https://doi.org/10.1093/jnci/djn088
Leyvraz, Serge ; Pampallona, Sandro ; Martinelli, Giovanni ; Ploner, Ferdinand ; Perey, Lucien ; Aversa, Savina ; Peters, Solange ; Brunsvig, Paal ; Montes, Ana ; Lange, Andrzej ; Yilmaz, Ugur ; Rosti, Giovanni. / A threefold dose intensity treatment with ifosfamide, carboplatin, and etoposide for patients with small cell lung cancer : A randomized trial. In: Journal of the National Cancer Institute. 2008 ; Vol. 100, No. 8. pp. 533-541.
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title = "A threefold dose intensity treatment with ifosfamide, carboplatin, and etoposide for patients with small cell lung cancer: A randomized trial",
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.",
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TY - JOUR

T1 - A threefold dose intensity treatment with ifosfamide, carboplatin, and etoposide for patients with small cell lung cancer

T2 - A randomized trial

AU - Leyvraz, Serge

AU - Pampallona, Sandro

AU - Martinelli, Giovanni

AU - Ploner, Ferdinand

AU - Perey, Lucien

AU - Aversa, Savina

AU - Peters, Solange

AU - Brunsvig, Paal

AU - Montes, Ana

AU - Lange, Andrzej

AU - Yilmaz, Ugur

AU - Rosti, Giovanni

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

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