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Clinical Trial
. 2015 Oct;106(10):1414-20.
doi: 10.1111/cas.12764. Epub 2015 Sep 21.

Phase I/II Trial of Chemoradiotherapy With Concurrent S-1 and Cisplatin for Clinical Stage II/III Esophageal Carcinoma (JCOG 0604)

Free PMC article
Clinical Trial

Phase I/II Trial of Chemoradiotherapy With Concurrent S-1 and Cisplatin for Clinical Stage II/III Esophageal Carcinoma (JCOG 0604)

Makoto Tahara et al. Cancer Sci. .
Free PMC article


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.

Keywords: Chemoradiotherapy; S-1; cisplatin; esophageal carcinoma; stage II/III.


Figure 1
Figure 1
Patient flow diagram of phase I/II trial of chemoradiotherapy with concurrent S-1 and cisplatin (CDDP) for clinical stage II/III esophageal carcinoma. DLT, dose-limiting toxicity; PS, performance status; RD, recommended dose.
Figure 2
Figure 2
Clinical outcomes for patients with clinical stage II/III esophageal carcinoma who participated in phase I/II trial of chemoradiotherapy and concurrent S-1 and cisplatin. (a) Progression-free survival (PFS) in all eligible patients (n = 43). (b) PFS in patients in phase II of trial (n = 37). (c) Overall survival (OS) in all eligible patients (n = 43). (d) OS in patients in phase II of trial (n = 37).

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