title: High-dose chemotherapy for patients with high-risk breast cancer: a clinical and economic assessment using a quality-adjusted survival analysis.
abstract: OBJECTIVE
  The benefit of high-dose chemotherapy (HDC) has not been clearly demonstrated. It may offer disease-free survival improvement at the expense of major toxicity and increasing cost. We evaluated the trade-offs between toxicity, relapse, and costs using a quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis.
  
  
  METHODS
  The analysis was conducted in the context of a randomized trial (PEGASE 01) evaluating the benefit of HDC for 314 patients with high-risk breast cancer. A Q-TWiST analysis was first performed to compare HDC with standard chemotherapy. We then used the results of this Q-TWiST analysis to inform a cost per quality-adjusted life-year (QALY) comparison between treatments.
  
  
  RESULTS
  Q-TWiST durations were in favor of HDC, whatever the weighting coefficients used for the analysis. This benefit was significant when the weighting coefficient related to the time spent after relapse was low (<0.38). For quite high values of this coefficient (>0.78), HDC offered no benefit. For intermediate values, the results depended on the weighting coefficient attributed to the toxicity period. The incremental cost per QALY ranged from 12,691euro/QALY to 26,439euro/QALY, according to the coefficients used to weight toxicity and relapse.
  
  
  CONCLUSIONS
  The benefits of HDC outweigh the burdens of treatment for a wide range of utility coefficients. Economic impact is not a barrier to HDC diffusion in this situation. Nevertheless, no significant benefit was demonstrated for a certain range of utility values.
authors.affiliation: INSERM, Unit Research 379, Marseilles, France. marino@marseille.inserm.fr
authors.forename: Patricia
authors.initials: P
authors.lastname: Marino
authors.forename: Henri
authors.initials: H
authors.lastname: Roché
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Moatti
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000191:economics; D003362:Cost-Benefit Analysis; D004334:Drug Administration Schedule; D016527:Drug Costs; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D008875:Middle Aged; D019057:Quality-Adjusted Life Years; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis