title: Treatment-related death in patients with small-cell lung cancer in phase III trials over the last two decades.
abstract: BACKGROUND
  Treatment-related death (TRD) remains a serious problem in small-cell lung cancer (SCLC), despite recent improvements in supportive care. However, few studies have formally assessed time trends in the proportion of TRD over the past two decades. The aim of this study was to determine the frequency and pattern of TRD over time.
  
  
  METHODS
  We examined phase 3 trials conducted between 1990 and 2010 to address the role of systemic treatment for SCLC. The time trend was assessed using linear regression analysis.
  
  
  RESULTS
  In total, 97 trials including nearly 25,000 enrolled patients were analyzed. The overall TRD proportion was 2.95%. Regarding the time trend, while it was not statistically significant, it tended to decrease, with a 0.138% decrease per year and 2.76% decrease per two decades. The most common cause of death was febrile neutropenia without any significant time trend in its incidence over the years examined (p = 0.139). However, deaths due to febrile neutropenia as well as all causes in patients treated with non-platinum chemotherapy increased significantly (p = 0.033).
  
  
  CONCLUSIONS
  The overall TRD rate has been low, but not negligible, in phase III trials for SCLC over the past two decades.
authors.affiliation: Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Ochi
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Hotta
authors.forename: Nagio
authors.initials: N
authors.lastname: Takigawa
authors.forename: Isao
authors.initials: I
authors.lastname: Oze
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Eiki
authors.initials: E
authors.lastname: Ichihara
authors.forename: Akiko
authors.initials: A
authors.lastname: Hisamoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tabata
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D003710:Demography; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D016032:Randomized Controlled Trials as Topic; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000401:mortality*; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents