1234PD - Randomized phase III trial of S-1 plus cisplatin versus docetaxel plus cisplatin for advanced non-small-cell lung cancer (TCOG0701)

Date 30 September 2012
Event ESMO Congress 2012
Session NSCLC, metastatic
Topics Anticancer agents
Non-small-cell lung cancer
Biological therapy
Presenter Hiroshi Sakai
Authors H. Sakai1, A. Gemma2, K. Kubota3, M. Nishio4, H. Okamoto5, A. Inoue6, H. Isobe7, K. Kobayashi8, M. Takeuchi9, S. Kudoh10
  • 1Thoracic Oncology, Saitama Cancer Center, 362-0806 - Saitama/JP
  • 2Nippon Medical School, Tokyo/JP
  • 3Internal Medicine, Nippon Medical School, Tokyo/JP
  • 4Thoracic Oncology Center, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 135-8550 - Tokyo/JP
  • 5Department Of Respiratory Medicine, Yokohama Municipal Citizen's Hospital, JP-240-8555 - Yokohama/JP
  • 6Department Of Respiratory Medicine, Tohoku University, JP-980-8575 - Sendai/JP
  • 7Clinical Oncology, KKR Sapporo Medical Center, 062-0931 - Sapporo/JP
  • 8Respiratory Medicine, Saitama International Medical Center, 350-1298 - Saitama/JP
  • 9Biostatistics And Pharmaceutical Medicine, Kitasato University School of Pharmacy, Tokyo/JP
  • 10Respiratory Medicine, Fukujuji Hospital, Tokyo/JP




Quality of life (QOL) should be an explicit priority throughout the course of care for patients with advanced non-small-cell lung cancer (NSCLC). Docetaxel plus cisplatin (DP) is the only third-generation regimen that has demonstrated statistically significant improvements in overall survival and QOL by a head-to-head comparison with a second-generation regimen (vindesine plus cisplatin) in patients with advanced NSCLC. S-1 plus cisplatin (SP) has shown activity and good tolerability in phase II settings.


Patients with previously untreated stage IIIB or IV NSCLC, an ECOG PS of 0-1 and adequate organ functions were randomly assigned to receive either oral S-1 80 mg/m2/day (40 mg/m2 b.i.d.) on days 1 to 21 plus cisplatin 60 mg/m2 on day 8 every 5 weeks or docetaxel 60 mg/m2 on day 1 plus cisplatin 80 mg/m2 on day 1 every 3 weeks, both up to 6 cycles. The primary endpoint was overall survival (OS). A non-inferiority study design was employed; the upper confidence interval (CI) limit of the hazard ratio (HR) was <1.322. Secondary endpoints included progression-free survival (PFS), response, safety, and QOL.


From April 2007 through December 2008, 608 patients were randomly assigned to SP (n = 303) or DP (n = 305) at 66 sites in Japan. Patient demographics were well balanced between the two groups. Two interim analyses were preplanned. At the final analysis, a total of 480 deaths had occurred. The primary endpoint was met. OS in the SP arm was non-inferior to that in the DP arm (median survival, 16.1 vs. 17.1 months, respectively; HR = 1.013; 96.4% confidence interval, 0.837-1.227). PFS was 4.9 months in the SP arm and 5.2 months in the DP arm. The rates of febrile neutropenia (7.4% vs. 1.0%), grade 3/4 neutropenia (73.4% vs. 22.9%), grade 3/4 infection (14.5% vs. 5.3%), and grade 1/2 alopecia (59.3% vs. 12.3%) were significantly lower in the SP arm than in the DP arm. In terms of physical functioning and global functioning on the EORTC QLQ-C30 and lung cancer module (LC-13), QOL was worse in the DP arm (repeated measures ANOVA: p < 0.01).


S-1 plus cisplatin is a standard first-line chemotherapeutic regimen for advanced NSCLC.


M. Nishio: HONORARIA: Chugai Pharma.

K. Kobayashi: HONORARIA: a reasonal payment for lectuture speech from Taiho Pharmaceutical Company.


All other authors have declared no conflicts of interest.