title: Mortality in the randomized, controlled lung intergroup trial of isotretinoin.
abstract: In 2001, we reported that mortality may have been higher with isotretinoin (30 mg/d for 3 years) than with placebo in the subgroup of current smokers among the 1,166 patients with definitively resected early-stage non-small cell lung cancer who participated in the randomized, controlled Lung Intergroup Trial. We report the overall and cause (cancer, cardiovascular disease, or other)-specific mortality associated with long-term isotretinoin after an extended median follow-up of 6.2 years that included the capture of cause-of-death data from 428 deceased patients. Overall mortality was 36.7% in each of the two trial arms, about two thirds related to cancer and one third to other or unknown causes. Overall and cancer deaths increased in current smokers in the isotretinoin arm during the treatment and the extended follow-up period. No mortality end point increased among never smokers and former smokers taking isotretinoin, and cancer deaths decreased marginally in this combined subgroup. Isotretinoin also increased deaths from cardiovascular disease in current smokers. The present analysis supports the safety of protracted isotretinoin use in the combined group of never smokers and former smokers, which has important public health implications, for example, for treating acne in young people. The increased mortality in current smokers in this study is further evidence of the multifaceted danger of active smoking. The overall indications of this study have public health implications for treating acne in young people and other uses of retinoids in smokers.
authors.affiliation: Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston, 77030-4009, USA. jjlee@mdanderson.org
authors.forename: J Jack
authors.initials: JJ
authors.lastname: Lee
authors.forename: Lei
authors.initials: L
authors.lastname: Feng
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Reshef
authors.forename: Anita L
authors.initials: AL
authors.lastname: Sabichi
authors.forename: Brendell
authors.initials: B
authors.lastname: Williams
authors.forename: Waree
authors.initials: W
authors.lastname: Rinsurongkawong
authors.forename: Ignacio I
authors.initials: II
authors.lastname: Wistuba
authors.forename: Reuben
authors.initials: R
authors.lastname: Lotan
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
mesh_terms: D000152:Acne Vulgaris / Q000188:drug therapy; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000401:mortality* / Q000601:surgery; D002318:Cardiovascular Diseases / Q000401:mortality*; D002423:Cause of Death; D003043:Cocarcinogenesis; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007239:Infections / Q000401:mortality; D015474:Isotretinoin / Q000009:adverse effects* / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000401:mortality*; D011013:Pneumonectomy; D016016:Proportional Hazards Models; D012907:Smoking / Q000009:adverse effects*
chemical_list: D000970:Antineoplastic Agents; D015474:Isotretinoin