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/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.
authors.affiliation: Centre Pluridisciplinaire d'Oncologie, University Hospital, Rue du Bugnon 46, 1011 Lausanne, Switzerland. serge.leyvraz@chuv.ch
authors.forename: Serge
authors.initials: S
authors.lastname: Leyvraz
authors.forename: Sandro
authors.initials: S
authors.lastname: Pampallona
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Ploner
authors.forename: Lucien
authors.initials: L
authors.lastname: Perey
authors.forename: Savina
authors.initials: S
authors.lastname: Aversa
authors.forename: Solange
authors.initials: S
authors.lastname: Peters
authors.forename: Paal
authors.initials: P
authors.lastname: Brunsvig
authors.forename: Ana
authors.initials: A
authors.lastname: Montes
authors.forename: Andrzej
authors.initials: A
authors.lastname: Lange
authors.forename: Ugur
authors.initials: U
authors.lastname: Yilmaz
authors.forename: Giovanni
authors.initials: G
authors.lastname: Rosti
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000401:mortality; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D015994:Incidence; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011379:Prognosis; D012107:Research Design; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide; D016190:Carboplatin; D007069:Ifosfamide