Exploratory phase II trial in a multicenter setting to evaluate the clinical value of a chemosensitivity test in patients with gastric cancer (JACCRO-GC 04, Kubota memorial trial)

Nobuhiko Tanigawa, Hiroki Yamaue, Shigekazu Ohyama, Shinichi Sakuramoto, Takao Inada, Yasuhiro Kodera, Yuukou Kitagawa, Kenji Omura, Masanori Terashima, Yuh Sakata, Atsushi Nashimoto, Toshiharu Yamaguchi, Keisho Chin, Eiji Nomura, San Woong Lee, Masahiro Takeuchi, Masashi Fujii, Toshifusa Nakajima

Research output: Contribution to journalArticle

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Abstract

Background: Although postoperative adjuvant chemotherapy with S-1, an oral fluoropyrimidine, has become a standard of care for gastric cancer in Japan, nonresponders may suffer from the cost and adverse reactions without clinical benefit. This multicenter exploratory phase II trial was conducted to see whether a chemosensitivity test, the collagen gel droplet embedded culture drug sensitivity test (CD-DST), can adequately select patients for chemotherapy. Methods: The CD-DST using four different concentrations of 5-fluorouracil was conducted with resected specimens from preregistered patients who underwent gastrectomy with D2 or more extensive lymphadenectomy. Patients who were histopathologically confirmed to have stage II or greater disease without distant metastasis were eligible for final enrollment. All patients underwent protocol-specified adjuvant chemotherapy with S-1. Three-year relapse-free survival was compared between patients determined as sensitive by the CD-DST (responders) and those deemed insensitive (nonresponders). Appropriate cutoff values for in vitro growth inhibition were defined when the hazard ratio for relapse in responders and the log-rank P values were at their minimum. Results: Of the 311 patients enrolled, 14 were ineligible and 27 failed to start the protocol treatment. The CD-DST failed in 64 other patients, and survival analyses were conducted with the remaining 206 patients (39 stage II disease, 155 stage III disease, and 12 stage IV disease). The outcome of patients who were determined to be responders was significantly superior to that of nonresponders regardless of the 5-fluorouracil concentrations, although no differences in clinicopathologic characteristics were observed between the two groups, except for age. Conclusions: The CD-DST identified those who benefit from adjuvant chemotherapy. It deserves further evaluation in the setting of a prospective randomized trial. ClinicalTrials.gov identifier: NCT00287755

Original languageEnglish
JournalGastric Cancer
DOIs
Publication statusAccepted/In press - 2015 Sep 18

Fingerprint

Stomach Neoplasms
Adjuvant Chemotherapy
Fluorouracil
Recurrence
Gastrectomy
Standard of Care
Survival Analysis
Clinical Protocols
Lymph Node Excision
Japan
Collagen
Age Groups
Gels
Neoplasm Metastasis
Costs and Cost Analysis
Drug Therapy
Survival
Growth
Pharmaceutical Preparations

Keywords

  • Appropriate cutoff values
  • Chemosensitivity test
  • Nonresponder
  • Relapse-free survival
  • Responder

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology
  • Cancer Research

Cite this

Exploratory phase II trial in a multicenter setting to evaluate the clinical value of a chemosensitivity test in patients with gastric cancer (JACCRO-GC 04, Kubota memorial trial). / Tanigawa, Nobuhiko; Yamaue, Hiroki; Ohyama, Shigekazu; Sakuramoto, Shinichi; Inada, Takao; Kodera, Yasuhiro; Kitagawa, Yuukou; Omura, Kenji; Terashima, Masanori; Sakata, Yuh; Nashimoto, Atsushi; Yamaguchi, Toshiharu; Chin, Keisho; Nomura, Eiji; Lee, San Woong; Takeuchi, Masahiro; Fujii, Masashi; Nakajima, Toshifusa.

In: Gastric Cancer, 18.09.2015.

Research output: Contribution to journalArticle

Tanigawa, N, Yamaue, H, Ohyama, S, Sakuramoto, S, Inada, T, Kodera, Y, Kitagawa, Y, Omura, K, Terashima, M, Sakata, Y, Nashimoto, A, Yamaguchi, T, Chin, K, Nomura, E, Lee, SW, Takeuchi, M, Fujii, M & Nakajima, T 2015, 'Exploratory phase II trial in a multicenter setting to evaluate the clinical value of a chemosensitivity test in patients with gastric cancer (JACCRO-GC 04, Kubota memorial trial)', Gastric Cancer. https://doi.org/10.1007/s10120-015-0506-z
Tanigawa, Nobuhiko ; Yamaue, Hiroki ; Ohyama, Shigekazu ; Sakuramoto, Shinichi ; Inada, Takao ; Kodera, Yasuhiro ; Kitagawa, Yuukou ; Omura, Kenji ; Terashima, Masanori ; Sakata, Yuh ; Nashimoto, Atsushi ; Yamaguchi, Toshiharu ; Chin, Keisho ; Nomura, Eiji ; Lee, San Woong ; Takeuchi, Masahiro ; Fujii, Masashi ; Nakajima, Toshifusa. / Exploratory phase II trial in a multicenter setting to evaluate the clinical value of a chemosensitivity test in patients with gastric cancer (JACCRO-GC 04, Kubota memorial trial). In: Gastric Cancer. 2015.
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AU - Tanigawa, Nobuhiko

AU - Yamaue, Hiroki

AU - Ohyama, Shigekazu

AU - Sakuramoto, Shinichi

AU - Inada, Takao

AU - Kodera, Yasuhiro

AU - Kitagawa, Yuukou

AU - Omura, Kenji

AU - Terashima, Masanori

AU - Sakata, Yuh

AU - Nashimoto, Atsushi

AU - Yamaguchi, Toshiharu

AU - Chin, Keisho

AU - Nomura, Eiji

AU - Lee, San Woong

AU - Takeuchi, Masahiro

AU - Fujii, Masashi

AU - Nakajima, Toshifusa

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N2 - Background: Although postoperative adjuvant chemotherapy with S-1, an oral fluoropyrimidine, has become a standard of care for gastric cancer in Japan, nonresponders may suffer from the cost and adverse reactions without clinical benefit. This multicenter exploratory phase II trial was conducted to see whether a chemosensitivity test, the collagen gel droplet embedded culture drug sensitivity test (CD-DST), can adequately select patients for chemotherapy. Methods: The CD-DST using four different concentrations of 5-fluorouracil was conducted with resected specimens from preregistered patients who underwent gastrectomy with D2 or more extensive lymphadenectomy. Patients who were histopathologically confirmed to have stage II or greater disease without distant metastasis were eligible for final enrollment. All patients underwent protocol-specified adjuvant chemotherapy with S-1. Three-year relapse-free survival was compared between patients determined as sensitive by the CD-DST (responders) and those deemed insensitive (nonresponders). Appropriate cutoff values for in vitro growth inhibition were defined when the hazard ratio for relapse in responders and the log-rank P values were at their minimum. Results: Of the 311 patients enrolled, 14 were ineligible and 27 failed to start the protocol treatment. The CD-DST failed in 64 other patients, and survival analyses were conducted with the remaining 206 patients (39 stage II disease, 155 stage III disease, and 12 stage IV disease). The outcome of patients who were determined to be responders was significantly superior to that of nonresponders regardless of the 5-fluorouracil concentrations, although no differences in clinicopathologic characteristics were observed between the two groups, except for age. Conclusions: The CD-DST identified those who benefit from adjuvant chemotherapy. It deserves further evaluation in the setting of a prospective randomized trial. ClinicalTrials.gov identifier: NCT00287755

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KW - Appropriate cutoff values

KW - Chemosensitivity test

KW - Nonresponder

KW - Relapse-free survival

KW - Responder

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