title: Identification of adverse events that have a negative impact on quality of life in a clinical trial comparing docetaxel versus S-1 with cisplatin in lung cancer.
abstract: OBJECTIVE
  In the CATS (Cisplatin And TS-1) randomized trial comparing cisplatin plus either docetaxel (DP arm) or TS-1 (SP arm) in lung cancer, efficacy was found to be equivalent but the global quality of life (QOL) score was higher in the SP arm. The purpose of the current study was to identify which of the adverse events (AEs) contributed to the deterioration of QOL.
  
  
  METHODS
  QOL and AE data from the CATS trial were used to quantitatively analyze the relationship between deterioration of QOL score and occurrence of AEs. Subtracted values of the QOL score from post-chemotherapy to pre-chemotherapy were fully compared between patients with or without each AE (Student's t test, significance level = 0.001). Multivariate linear regression analysis was also performed. Analysis of variance was performed to identify whether grade of AE(s) might be significantly correlated with the deterioration of the QOL score (significance level of 0.05).
  
  
  RESULTS
  As expected, gastrointestinal (GI) toxicities were associated with worsening of a variety of QOL items in both trial arms, detected by both univariate and multivariate analysis (p < 0.001 and p < 0.0001, respectively). Multivariate analysis unpredictably indicated that an increase in serum bilirubin level was the only AE that was uniquely associated with worsening of physical functioning (p = 0.0002), cognitive functioning (p < 0.0001), and financial problems (p = 0.0005) in the DP arm, although not in the SP arm. GI toxicities tended to be prolonged in the SP arm.
  
  
  CONCLUSIONS
  An increase in serum bilirubin level may contribute to the worse global QOL of subjects in the DP arm in the CATS trial. The method we used here may be a unique approach to identify unpredictable AE(s) that worsen the QOL of patients treated by chemotherapy.
authors.affiliation: Global Health Research Coordinating Center, Kanagawa Academy of Science and Technology, KSP East 3F 309, 3-2-1, Sakado, Takatsu-ku, Kawasaki, Kanagawa, 213-0012, Japan. gh-aotani@newkast.or.jp.
authors.forename: Eriko
authors.identifier: http://orcid.org/0000-0001-9843-949X
authors.initials: E
authors.lastname: Aotani
authors.affiliation: Clinical Trial Coordinating Center, Kitasato Academic Research Organization, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8642, Japan.
authors.forename: Tetsutaro
authors.initials: T
authors.lastname: Hamano
authors.affiliation: Department of Pulmonary Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Gemma
authors.affiliation: Biostatistics and Pharmaceutical Medicine, Department of Clinical Medicine, School of Pharmacy, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takeuchi
authors.affiliation: Department of Preventive Medicine and Public Health, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Takebayashi
authors.affiliation: Department of Pulmonary Medicine, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, 350-1298, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Kobayashi
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001663:Bilirubin / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003072:Cognition Disorders / Q000139:chemically induced; D000077143:Docetaxel; D004338:Drug Combinations; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D011788:Quality of Life; D043823:Taxoids / Q000009:adverse effects*; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D004338:Drug Combinations; D043823:Taxoids; C079198:S 1 (combination); D005641:Tegafur; D000077143:Docetaxel; D010094:Oxonic Acid; D002945:Cisplatin; D001663:Bilirubin
keywords: Adverse events; Cancer chemotherapy; Lung cancer; Quality of life