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)

• Published in: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association Vol. 19; no. 2; pp. 350 - 360
• Main Authors: Tanigawa, Nobuhiko, Yamaue, Hiroki, Ohyama, Shigekazu, Sakuramoto, Shinichi, Inada, Takao, Kodera, Yasuhiro, Kitagawa, Yuko, Omura, Kenji, Terashima, Masanori, Sakata, Yuh, Nashimoto, Atsushi, Yamaguchi, Toshiharu, Chin, Keisho, Nomura, Eiji, Lee, San-Woong, Takeuchi, Masahiro, Fujii, Masashi, Nakajima, Toshifusa
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.04.2016; Springer Nature B.V
• Subjects: Abdominal Surgery; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer Research; Disease-Free Survival; Drug Combinations; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor - methods; Female; Fluorouracil - administration & dosage; Fluorouracil - pharmacology; Gastrectomy; Gastric cancer; Gastroenterology; Gene Expression Regulation, Neoplastic; Humans; Male; Medicine; Medicine & Public Health; Middle Aged; Oncology; Original; Original Article; Oxonic Acid - administration & dosage; Oxonic Acid - therapeutic use; Stomach Neoplasms - drug therapy; Stomach Neoplasms - genetics; Stomach Neoplasms - mortality; Stomach Neoplasms - surgery; Surgical Oncology; Tegafur - administration & dosage; Tegafur - therapeutic use; Treatment Outcome; Chemosensitivity test; Appropriate cutoff values; Nonresponder; Relapse-free survival; Responder
• ISSN: 1436-3291; 1436-3305
• DOI: 10.1007/s10120-015-0506-z

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