A phase II study of preoperative chemotherapy with docetaxel, cisplatin, and S-1 followed by gastrectomy with D2 plus para-aortic lymph node dissection for gastric cancer with extensive lymph node metastasis: JCOG1002.
BACKGROUND
Gastric cancer with extensive lymph node metastasis is commonly considered unresectable, with a poor prognosis. We previously reported the results of the use of cisplatin and S-1 as preoperative chemotherapy for gastric cancer with extensive lymph node metastasis; docetaxel, cisplatin, and S-1 (DCS) have now been investigated for the same purpose.


METHODS
Patients received two or three 28-day cycles of DCS therapy (docetaxel at 40 mg/m2and cisplatin at 60 mg/m2on day 1, S-1 at 40 mg/m2twice daily for 2 weeks) followed by gastrectomy with D2 plus para-aortic nodal dissection. After R0 resection, S-1 chemotherapy was given for 1 year. The primary end point was the response rate (RR) to preoperative chemotherapy determined by central peer review according to the Response Evaluation Criteria in Solid Tumors version 1.0. The planned sample size was 50, with one-sided alpha of 10 %, power of 80 %, expected RR of 80 %, and threshold of 65 %.


RESULTS
Between July 2011 and May 2013, 53 patients were enrolled, of whom 52 were eligible. The clinical RR was 57.7 % [30/52, 80 % confidence interval 47.9-67.1 %, p = 0.89], and R0 resection was achieved in 84.6 % of patients (44/52). Common grade 3 or grade 4 adverse events during DCS therapy were leukocytopenia (18.9 %), neutropenia (39.6 %), and hyponatremia (15.1 %). The common grade 3 or grade 4 surgical morbidity was abdominal infection (10.2 %). The pathological RR was 50.0 % (26/52).


CONCLUSIONS
Preoperative DCS therapy was feasible but did not show a sufficient RR. Preoperative cisplatin and S-1 therapy is still considered the tentative standard treatment for this population until survival results are known.
Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan. seito@aichi-cc.jp.
Seiji
S
Ito
Department of Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
Takeshi
T
Sano
JCOG Data Center, National Cancer Center, Tokyo, Japan.
Junki
J
Mizusawa
Department of Gastroenterology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
Daisuke
D
Takahari
JCOG Operations Office, National Cancer Center, Tokyo, Japan.
Hiroshi
H
Katayama
Gastric Surgery Division, National Cancer Center Hospital, Tokyo, Japan.
Hitoshi
H
Katai
Division of Gastroenterological Surgery, Saitama Cancer Center, Saitama, Japan.
Yoshiyuki
Y
Kawashima
Gastric Surgery Division, National Cancer Center Hospital East, Kashiwa, Japan.
Takahiro
T
Kinoshita
Division of Gastric Surgery, Shizuoka Cancer Center, Nagaizumi, Japan.
Masanori
M
Terashima
Department of Surgery, Niigata Cancer Center Hospital, Niigata, Japan.
Atsushi
A
Nashimoto
Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan.
Mikihito
M
Nakamori
Department of Diagnostic Radiology, Gunma Prefectural Cancer Center, Ota, Japan.
Hiroaki
H
Onaya
Division of Upper Gastrointestinal Surgery, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan.
Mitsuru
M
Sasako
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D000077143:Docetaxel; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D005743:Gastrectomy; D006801:Humans; D007414:Intestinal Neoplasms / Q000556:secondary / Q000628:therapy*; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000473:pathology / Q000601:surgery*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010094:Oxonic Acid / Q000008:administration & dosage; D011300:Preoperative Care; D011379:Prognosis; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000473:pathology / Q000628:therapy*; D043823:Taxoids / Q000008:administration & dosage; D005641:Tegafur / Q000008:administration & dosage
D004338:Drug Combinations; D043823:Taxoids; C079198:S 1 (combination); D005641:Tegafur; D000077143:Docetaxel; D010094:Oxonic Acid; D002945:Cisplatin
Adjuvant chemotherapy; Gastrectomy; Lymphatic metastasis; Stomach neoplasms