A Threefold Dose Intensity Treatment With Ifosfamide, Carboplatin, and Etoposide for Patients With Small Cell Lung Cancer: A Randomized Trial

Autor: Leyvraz, S., Pampallona, S., Martinelli, G., Ploner, F., Perey, L., Aversa, S., Peters, S., Brunsvig, P., Montes, A., Lange, A., Yilmaz, U., Rosti, G., Marrow, Transplantation
Přispěvatelé: Solid Tumors Working Party of the European Group for Blood, Marrow, Transplantation, Aversa, S., Brunsvig, P., Buxhofer, V., Crown, J., De Bock, R., Demirer, T., Kühr, T., Lange, A., Leyvraz, S., Martinelli, G., Montes, A., Piazza, E., Ploner, F., Rosti, G., Rudolf, C., Schneider, CP., van Klaveren, R., Yilmaz, U., Parmar, M., Thatcher, N., Hansen, H.
Rok vydání: 2008
Předmět:
Adult
Male
Cancer Research
medicine.medical_specialty
Lung Neoplasms
medicine.medical_treatment
Filgrastim
Neutropenia
Gastroenterology
Drug Administration Schedule
Carboplatin
chemistry.chemical_compound
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
Odds Ratio
medicine
Humans
Ifosfamide
Carcinoma
Small Cell
Lung cancer
Antineoplastic Agents
Alkylating
Etoposide
Aged
Chemotherapy
Antineoplastic Agents
Alkylating/administration & dosage
Antineoplastic Agents
Alkylating/adverse effects
Antineoplastic Agents
Phytogenic/administration & dosage
Antineoplastic Agents
Phytogenic/adverse effects
Antineoplastic Combined Chemotherapy Protocols/adverse effects
Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Carboplatin/administration & dosage
Carboplatin/adverse effects
Carcinoma
Small Cell/drug therapy
Carcinoma
Small Cell/mortality
Dose-Response Relationship
Drug
Etoposide/administration & dosage
Etoposide/adverse effects
Female
Hematologic Diseases/chemically induced
Ifosfamide/administration & dosage
Ifosfamide/adverse effects
Incidence
Lung Neoplasms/drug therapy
Lung Neoplasms/mortality
Middle Aged
Prognosis
Research Design
Survival Analysis
Treatment Outcome
business.industry
medicine.disease
Antineoplastic Agents
Phytogenic
Hematologic Diseases
Surgery
Oncology
chemistry
Toxicity
business
medicine.drug
Zdroj: Journal of the National Cancer Institute, vol. 100, no. 8, pp. 533-541
ISSN: 1460-2105
0027-8874
DOI: 10.1093/jnci/djn088
Popis: 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/m(2), paclitaxel at 175 mg/m(2), 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 > or = 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.
Databáze: OpenAIRE
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