title: Nedaplatin plus docetaxel versus cisplatin plus docetaxel for advanced or relapsed squamous cell carcinoma of the lung (WJOG5208L): a randomised, open-label, phase 3 trial.
abstract: BACKGROUND
  The combination of nedaplatin, a cisplatin derivative, and docetaxel showed promising activity for advanced squamous cell lung carcinoma in a previous phase 1-2 study. We compared nedaplatin plus docetaxel with cisplatin plus docetaxel in patients with previously untreated advanced or relapsed squamous cell lung carcinoma to determine effects on overall survival.
  
  
  METHODS
  We did a randomised, open-label, phase 3 study at 53 institutions in Japan. Eligibility criteria included pathologically proven squamous cell lung cancer with stage IIIB/IV or postoperative recurrence, age 20-74 years, Eastern Cooperative Oncology Group performance status of 0-1, no previous chemotherapy or recurrence more than a year after previous adjuvant chemotherapy, and adequate organ function. Patients were randomly assigned (1:1) to 100 mg/m(2) nedaplatin and 60 mg/m(2) docetaxel intravenously, or 80 mg/m(2) cisplatin and 60 mg/m(2) docetaxel, every 3 weeks for four to six cycles (at the treating oncologist's discretion). Randomisation was done centrally at the West Japan Oncology Group data centre via a computer-generated allocation sequence with dynamic minimisation that balanced stage (IIIB/IV or postoperative recurrent), sex, and institution. The primary endpoint was overall survival in the modified intention-to-treat population (ie, all patients who were randomly assigned and met the inclusion criteria). Safety analyses were done in all randomly assigned patients who received at least one dose of the study regimen. This trial is registered with the UMIN Clinical Trials Registry, number UMIN000002015, and is closed to new participants.
  
  
  RESULTS
  Between July 6, 2009, and July 26, 2012, 355 patients were randomly assigned. 349 patients were included in the modified intention-to-treat analysis (177 in the nedaplatin group and 172 in the cisplatin group). Overall survival was significantly longer in the nedaplatin group (median 13·6 months, 95% CI 11·6-15·6) than in the cisplatin group (11·4 months,10·2-12·2; hazard ratio 0·81, 95% CI 0·65-1·02; p=0·037, one-sided stratified log-rank test). Grade 3 or worse nausea (seven of 177 patients in the nedaplatin group and 25 of 175 in the cisplatin group), fatigue (six vs 20), hyponatraemia (24 vs 53), and hypokalaemia (four vs 15) were more frequent in the cisplatin group than in the nedaplatin group, whereas grade 3 or worse leucopenia (98 vs 77), neutropenia (146 vs 123), and thrombocytopenia (16 vs none) were more frequent in the nedaplatin group than in the cisplatin group. Treatment-related deaths occurred in four and three patients in nedaplatin and cisplatin groups, respectively.
  
  
  CONCLUSIONS
  Overall survival was significantly longer with nedaplatin plus docetaxel than with cisplatin plus docetaxel, and the regimens had different safety profiles. Nedaplatin plus docetaxel could be a new treatment option for advanced or relapsed squamous cell lung cancer.
  
  
  BACKGROUND
  West Japan Oncology Group and Sanofi.
authors.affiliation: Department of Respiratory Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Takehito
authors.initials: T
authors.lastname: Shukuya
authors.affiliation: Department of Biostatistics, Yokohama City University, Kanagawa, Japan.
authors.forename: Takeharu
authors.initials: T
authors.lastname: Yamanaka
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Centre, Fukuoka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Seto
authors.affiliation: Department of Clinical Oncology, Osaka City General Hospital, Osaka, Japan.
authors.forename: Haruko
authors.initials: H
authors.lastname: Daga
authors.affiliation: Department of Thoracic Oncology, National Cancer Centre Hospital East, Chiba, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Goto
authors.affiliation: Department of Respiratory Medicine and Medical Oncology, National Hospital Organisation Nagoya Medical Centre, Aichi, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Saka
authors.affiliation: Department of Pulmonary Medicine, Sendai Kousei Hospital, Miyagi, Japan.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Sugawara
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Respiratory Medicine, National Hospital Organisation Toneyama National Hospital, Osaka, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Yokota
authors.affiliation: Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Kaneda
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Kawaguchi
authors.affiliation: Department of Thoracic Surgery, Tokyo Medical University, Tokyo, Japan.
authors.forename: Seisuke
authors.initials: S
authors.lastname: Nagase
authors.affiliation: Department of Respiratory Medicine, Allergy, and Clinical Immunology, Graduate School of Medical Sciences, Nagoya City University, Aichi, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Oguri
authors.affiliation: Department of Medical Oncology, Hiroshima City Hospital, Hiroshima, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Iwamoto
authors.affiliation: Department of Respiratory Medicine, Kyoto-Katsura Hospital, Kyoto, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishimura
authors.affiliation: Department of Thoracic Oncology, Hyogo Cancer Center, Hyogo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hattori
authors.affiliation: Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakanishi
authors.affiliation: Third Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan. Electronic address: nbyamamo@wakayama-med.ac.jp.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamamoto
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D007564:Japan; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D012307:Risk Factors; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D043823:Taxoids; D000077143:Docetaxel; C053989:nedaplatin; D002945:Cisplatin