623P - Exploratory phase II trial assessing relevance of in vitro chemosensitivity test as a predictor of survival in gastric cancer undergoing adjuvant c...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Basic Science
Gastric Cancer
Translational Research
Presenter Hiroki Yamaue
Citation Annals of Oncology (2014) 25 (suppl_4): iv210-iv253. 10.1093/annonc/mdu334
Authors H. Yamaue1, T. Kubota2, N. Tanigawa3, S. Ohyama4, S. Sakuramoto5, T. Inada6, Y. Kitagawa2, T. Ochiai7, M. Terashima8, M. Gotoh9, Y. Yasuda10, A. Hara11, H. Kato12, J. Matsuyama13, Y. Kodera14, A. Nashimoto15, T. Yamaguchi16, M. Takeuchi17, M. Fujii18, T. Nakajima19
  • 1Second Department Of Surgery, Wakayama Medical University School of Medicine, 641-8510 - Wakayama/JP
  • 2Department Of Surgery, Keio University, Tokyo/JP
  • 3Department Of Surgery, Tanigawa Memorial Hospital, Ibaraki/JP
  • 4Dept. Of Surgery, National Hospital Organization, Kanazawa Medical Center, Kanazawa/JP
  • 5Department Of Gastroenterological Surgery, Saitama Medical University International Medical Center, Hidaka/JP
  • 6Department Of Surgery, Tochigi Cancer Center, Utsunomiya/JP
  • 7Surgery, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, 125-8512 - Tokyo/JP
  • 8Division Of Gastric Surgery, Shizuoka Cancer Center, Nagaizumi-cho/JP
  • 9Department Of Regenerative Surgery, Fukushima Medical University, Fukushima/JP
  • 10Department Of Surgery, Jichi Medical University Hospital, Shimotsuke/JP
  • 11Department Of Surgery, Saiseikai Suita Hospital, Suita/JP
  • 12Department Of Surgical Oncology, Dokkyo Medical University, Mibu-machi/JP
  • 13Department Of Surgery, Yao Municipal Hospital, Yao/JP
  • 14Department Of Surgery Ii, Nagoya University Graduate School of Medicine, 466-8550 - Nagoya/JP
  • 15Surgery, Niigata Cancer Center Hospital, Niigata/JP
  • 16Department Of Gastroenterological Surgery, Cancer Institute Hospital of JFCR, Tokyo/JP
  • 17Biostatistics And Pharmaceutical Medicine, Kitasato University School of Pharmacy, Tokyo/JP
  • 18Department Of Digestive Surgery, Nihon University School of Medicine, 101-8309 - Tokyo/JP
  • 19Department Of Surgical Oncology, Japan Clinical Cancer Research Organization, 104-0061 - Tokyo/JP

Abstract

Aim

Postoperative S-1 (a 5-FU derivative) monotherapy has become the standard for Stage II/III gastric cancer in Japan following a phase III trial designated ACTS-GC, which implies that S-1 is also given to the patients whose tumors may not be sensitive to 5-FU. A nationwide clinical trial, JACCRO-GC04, was conducted to explore whether individualization of the treatment is possible through chemosensitivity testing.

Methods

Using surgically resected specimens, the collagen gel droplet-embedded drug sensitivity test was performed at 5-FU concentrations (conc) of 0.2, 0.4, 1.0 and 2.0 µg/ml. Patients who underwent R0 resection for histologically proven stage II ∼ IV gastric cancer and for whom the chemosensitivity test was successful were eligible. All eligible patients were to receive adjuvant treatment with S-1 for 1 year at a dose of 80 mg/m2 bid for 4 weeks followed by 2 weeks rest. Optimal cut-off values at each 5-FU conc to decide on the chemosensitivity were to be sought within the study. Ultimate objective of the study was to prove the hypothesis that a significant difference in 3-year relapse-free survival (RFS), the primary endpoint, is observed between the responder (Res) and non-responder (Non).

Results

Between 2005 and 2013, 311 patients were enrolled, of which 206 were eligible. Hazard ratios (HR) for relapse in Res as compared with Non were calculated at various cut-off values of in vitro growth inhibition rates from 10% to 90% with an increment of 10%. The appropriate cut-off values could be defined based on HR <0.4 with narrow 95% confidence intervals and significant P value for each of the four different in vitro 5-FU conc, like 60% and 70% at 2.0 µg/ml, 50% and 60% at 1.0 µg/ml, 40% and 50% at 0.4 µg/ml, and 20% and 30% at 0.2 µg/ml. For instance, one of the appropriate cut-off values at 1.0 µg/ml was defined to be 50%, where HR for relapse in the 102 Res as compared with the 94 Non was 0.37. The 3-year RFS rate was 81.2% in Res and 60.0 % in Non.

Conclusions

The appropriate cut-off values classifying patients as Res or Non were found. The low HR for relapse indicates the in vitro drug sensitivity predicts efficacy of the postoperative S-1 treatment.

Disclosure

M. Fujii: Advisory board; Taiho Honarium; Taiho Travel Grant; JACCRO. All other authors have declared no conflicts of interest.