title: Phase I/II trial of chemoradiotherapy with concurrent S-1 and cisplatin for clinical stage II/III esophageal carcinoma (JCOG 0604).
abstract: We carried out a phase I/II trial of chemoradiotherapy concurrent with S-1 and cisplatin to determine the maximum tolerated dose and recommended dose and to evaluate the efficacy and safety of this treatment in patients with esophageal carcinoma. Thoracic esophageal cancer patients with clinical stage II/III disease, excluding T4, were eligible. Chemotherapy consisted of S-1 at a dose of 60-80 mg/m(2) /day on days 1-14, and cisplatin at 75 mg/m(2) on day 1, repeated twice every 4 weeks. Single daily radiation of 50.4 Gy was given in 28 fractions concurrently starting on day 1. Patients achieving an objective response after chemoradiotherapy underwent two additional cycles of chemotherapy. Patient accrual was terminated early due to slow enrolment after 44 patients were accrued. In the phase I part, two of six patients experienced dose-limiting toxicities at each level of S-1 (S-1 60 or 80 mg/m(2) /day). Considering treatment compliance, the recommended dose was determined to be S-1 60 mg/m(2) /day. The complete response rate, the primary endpoint of phase II, was 59.5% (22/37; 90% confidence interval, 44.6-73.1%; weighted threshold, 57.2%; P = 0.46 by the exact binomial test) on central review. In the phase II part, 3-year progression-free survival was 48.4%, with a 3-year overall survival of 61.9%. Grade 3 or 4 toxicity in phase II included leukopenia (57.9%), neutropenia (50%), hyponatremia (28.9%), anorexia (21.1%), anemia (18.4%), thrombocytopenia (18.4%), and febrile neutropenia (2.6%). No treatment-related deaths were observed. Although this combination showed acceptable toxicity and favorable 3-year survival, the study did not meet its primary endpoint. This trial was registered at the UMIN Clinical Trials Registry as UMIN000000710.
authors.affiliation: Department of Head and Neck Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan.|Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tahara
authors.affiliation: Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Fuse
authors.affiliation: Japan Clinical Oncology Group Data Center, National Cancer Center, Tokyo, Japan.
authors.forename: Junki
authors.initials: J
authors.lastname: Mizusawa
authors.affiliation: Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Sato
authors.affiliation: Department of Radiology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Nihei
authors.affiliation: Japan Clinical Oncology Group Operations Office, National Cancer Center, Tokyo, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kanato
authors.affiliation: Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Kato
authors.affiliation: Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamazaki
authors.affiliation: Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Muro
authors.affiliation: Keio Cancer Center, Keio University Hospital, Tokyo, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Takaishi
authors.affiliation: Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Narikazu
authors.initials: N
authors.lastname: Boku
authors.affiliation: Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.|Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ohtsu
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004338:Drug Combinations; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D010094:Oxonic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D005641:Tegafur / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D011725:Pyridines; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D002945:Cisplatin; C104201:gimeracil
keywords: Chemoradiotherapy; S-1; cisplatin; esophageal carcinoma; stage II/III