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Lancet Gastroenterol Hepatol. 2019 Jul;4(7):501-510. doi: 10.1016/S2468-1253(19)30083-4. Epub 2019 May 14.

Docetaxel plus cisplatin and S-1 versus cisplatin and S-1 in patients with advanced gastric cancer (JCOG1013): an open-label, phase 3, randomised controlled trial.

Author information

1
Comprehensive Cancer Center, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo, Japan; Department of Medical Oncology, Hamamatsu University School of Medicine, Shizuoka, Japan; Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan. Electronic address: yayamada@hosp.ncgm.go.jp.
2
Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan.
3
Japan Clinical Oncology Group Data Center and Operations Office, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan.
4
Department of Clinical Oncology, Aichi Cancer Center Hospital, Chikusa-ku, Nagoya, Aichi, Japan.
5
Department of Gastroenterology, Kanagawa Cancer Center Hospital, Asahi-ku, Yokohama, Kanagawa, Japan.
6
Department of Gastroenterology, Kitasato University School of Medicine, Minami, Sagamihara, Kanagawa, Japan.
7
Department of Gastroenterology, Hyogo Cancer Center, Akashi, Hyogo, Japan.
8
Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa-shi, Chiba, Japan.
9
Department of Medical Oncology, Kindai University, Faculty of Medicine, Osaka, Japan.
10
Department of Gastroenterology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan.
11
Department of Surgery, National Hospital Organization Kyoto Medical Center, Fushimi-ku, Kyoto, Japan.
12
Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan.
13
Department of Gastroenterology, Saitama Cancer Center, Inamachi, Kitaadachi-gun, Saitama, Japan.
14
Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan.
15
Department of Gastrointestinal Surgery, Kanagawa Cancer Center Hospital, Asahi-ku, Yokohama, Kanagawa, Japan.
16
Department of Surgery, Hyogo College of Medicine, Fushimi-ku Mukogawa-cho, Nishinomiya-shi, Hyogo, Japan.
17
Division of Gastric Surgery, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan.

Abstract

BACKGROUND:

We investigated the superiority of docetaxel plus cisplatin and S-1 compared with cisplatin and S-1 in chemotherapy-naive patients with advanced gastric cancer.

METHODS:

In this open-label, phase 3, randomised controlled trial, patients were recruited from 56 hospitals in Japan. We enrolled individuals aged 20-75 years who had unresectable or recurrent gastric cancer, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, had received no previous chemotherapy (except adjuvant chemotherapy completed 24 weeks before reccurence), radiotherapy, or hormonal therapy, could take drugs orally, and had adequate organ function. Patients were randomly assigned (1:1) to receive docetaxel plus cisplatin and S-1 (docetaxel 40 mg/m2 and cisplatin 60 mg/m2 on day 1 intravenously, and S-1 40-60 mg twice a day orally for 2 weeks, every 4 weeks) or cisplatin and S-1 (cisplatin 60 mg/m2 intravenously on day 8, and S-1 40-60 mg orally twice a day for 3 weeks, every 5 weeks). Randomisation was done centrally with the minimisation method, with a random component balancing for institution, ECOG performance status (0 vs 1), disease status at enrolment (unresectable vs recurrent), measurable lesion (yes vs no), number of metastatic sites (0-1 vs ≥2), and histological type (differentiated vs undifferentiated). Neither investigators or patients were masked to the study treatment. The primary endpoint was overall survival in the intention-to-treat population. The study is registered with UMIN-CTR, number UMIN000007652.

FINDINGS:

Between April 3, 2012, and March 18, 2016, 741 patients were randomly assigned to receive docetaxel plus cisplatin and S-1 (n=370) or cisplatin and S-1 (n=371). Median overall survival was 14·2 months (95% CI 12·9-15·9) in the docetaxel plus cisplatin and S-1 group and 15·3 months (14·2-16·2) in the cisplatin and S-1 group (hazard ratio [HR] 0·99 [95% CI 0·85-1·16]; one-sided stratified log-rank p=0·47). The most common grade 3 or worse adverse events were neutropenia (209 [59%] of 357 patients in the docetaxel plus cisplatin and S-1 group vs 117 [32%] of 365 patients in the cisplatin and S-1 group), leukopenia (120 [34%] vs 60 [16%]), and anorexia (94 [26%] vs 81 [22%]). The deaths of one patient in the cisplatin and S-1 group and in three patients in the docetaxel plus cisplatin and S-1 group were deemed treatment-related.

INTERPRETATION:

The addition of docetaxel to cisplatin and S-1 did not improve overall survival in chemotherapy-naive Japanese patients with advanced gastric cancer. Therefore, cisplatin and S-1 remains the standard first-line chemotherapy.

FUNDING:

Ministry of Health, Labour and Welfare and Japan Agency for Medical Research and Development.

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