title: Dose-intensive therapy for limited-stage small-cell lung cancer: long-term outcome.
abstract: OBJECTIVE
  To determine progression-free survival (PFS) and overall long-term survival for limited-stage small-cell lung cancer (SCLC) patients aged 60 years or younger who respond to first-line chemotherapy followed by high-dose combination alkylating agents (cyclophosphamide 5,625 mg/m(2), cisplatin 165 mg/m(2), and carmustine 480 mg/m(2)) with hematologic stem-cell support and chest and prophylactic cranial radiotherapy.
  
  
  METHODS
  Patients were selected on the basis of their continued response to first-line therapy, their relative lack of significant comorbidity, and their ability to obtain financial clearance.
  
  
  RESULTS
  Of 36 patients with stage III SCLC, nine patients (25%) had achieved a complete response (CR), 20 had achieved a near-CR, and seven had achieved a partial response before undergoing high-dose therapy. Toxicity included three deaths (8%). For all patients, the median PFS was 21 months. The 2- and 5-year survival rates after dose intensification were 53% (95% confidence interval [CI], 39% to 72%), and 41% (95% CI, 28% to 61%). Of the 29 patients who were in or near CR before undergoing high-dose therapy, 14 remain continuously progression-free a median of 61 months (range, 40 to 139 months) after high-dose therapy. Actuarial 2- and 5-year PFS rates were 57% (95% CI, 41% to 79%) and 53% (95% CI, 38% to 76%). By multivariate analysis, short intensive induction chemotherapy was associated with favorable outcome (P <.05).
  
  
  CONCLUSIONS
  Use of high-dose systemic therapy with intensive local-regional radiotherapy was associated with manageable treatment-related morbidity and mortality. Patients who were in or near CR before intensification are enjoying an unmaintained 5-year PFS rate of 53%. Late complications were infrequent, and most patients returned to full-time work and activity. A randomized comparison of this approach and conventional-dose therapy should define the use of dose intensification with hematopoietic support in patients with responding limited-stage SCLC.
authors.affiliation: Department of Medicine, Division of Biostatistics, Dana-Farber Cancer Institute, Boston, MA 02115, USA. anthony_elias@macmailgw.dfci.harvard.edu
authors.forename: A
authors.initials: A
authors.lastname: Elias
authors.forename: J
authors.initials: J
authors.lastname: Ibrahim
authors.forename: A T
authors.initials: AT
authors.lastname: Skarin
authors.forename: C
authors.initials: C
authors.lastname: Wheeler
authors.forename: M
authors.initials: M
authors.lastname: McCauley
authors.forename: L
authors.initials: L
authors.lastname: Ayash
authors.forename: P
authors.initials: P
authors.lastname: Richardson
authors.forename: L
authors.initials: L
authors.lastname: Schnipper
authors.forename: K H
authors.initials: KH
authors.lastname: Antman
authors.forename: E
authors.initials: E
authors.lastname: Frei
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage; D018288:Carcinoma, Small Cell / Q000628:therapy*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008175:Lung Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011879:Radiotherapy Dosage; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents