title: Adjuvant cisplatin-based chemotherapy in nonsmall-cell lung cancer: new insights into the effect on failure type via a multistate approach.
abstract: BACKGROUND
  Adjuvant cisplatin-based chemotherapy has become the standard therapy against resected nonsmall-cell lung cancer (NSCLC). Because of variable results on its late effect, we reanalyze the long-term data of the International Adjuvant Lung Cancer Trial (IALT) to describe in details the role of adjuvant chemotherapy.
  
  
  METHODS
  In the IALT, 1867 patients were randomized between adjuvant cisplatin-based chemotherapy and control, who were followed up for a median of 7.5 years. Of these, 1687 patients were enrolled from 132 centers accepting to report the times to cancer events. We used event history methodology to estimate the effects of adjuvant chemotherapy on the risks of local relapse, distant metastasis, and death.
  
  
  RESULTS
  Adjuvant chemotherapy was highly effective against local relapses [HR = 0.73; 95% confidence interval (CI) 0.60-0.90; P = 0.003] and nonbrain metastases (HR = 0.79; 95% CI 0.66-0.94; P = 0.008) but not against brain metastases (HR = 1.1; 95% CI 0.82-1.4; P = 0.61). The effect on noncancer mortality was nonsignificant during the first 5 years (HR = 1.1; 95% CI 0.81-1.5; P = 0.29), whereas the risk of noncancer mortality was subsequently higher with treatment (HR = 3.6; 95% CI 2.2-5.9; P < 0.001). This harmful effect, however, potentially concerned only about 2% of the patients at 8 years.
  
  
  CONCLUSIONS
  Adjuvant cisplatin-based chemotherapy reduced the risk of local relapse and of nonbrain metastasis, thereby improving survival. This treatment exerted no residual effect on mortality during the first 5 years, but a higher risk of noncancer mortality was found thereafter. Detailed long-term follow-up is strongly recommended for all patients in randomized trials evaluating adjuvant treatments in NSCLC.
authors.affiliation: Department of Biostatistics and Epidemiology. Electronic address: federico.rotolo@gustaveroussy.fr.
authors.forename: F
authors.initials: F
authors.lastname: Rotolo
authors.affiliation: Department of Biostatistics and Epidemiology.
authors.forename: A
authors.initials: A
authors.lastname: Dunant
authors.affiliation: Department of Medical Oncology.
authors.forename: T
authors.initials: T
authors.lastname: Le Chevalier
authors.affiliation: Department of Biostatistics and Epidemiology.
authors.forename: J-P
authors.initials: JP
authors.lastname: Pignon
authors.affiliation: Department of Radiation Oncology, Gustave Roussy, Villejuif, France.
authors.forename: R
authors.initials: R
authors.lastname: Arriagada
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D064420:Drug-Related Side Effects and Adverse Reactions / Q000473:pathology; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D016032:Randomized Controlled Trials as Topic
chemical_list: D002945:Cisplatin
keywords: adjuvant chemotherapy; cisplatin; failure pattern; multistate model; nonsmall-cell lung cancer; randomized trial