Phase I/II trial of chemoradiotherapy with concurrent S-1 and cisplatin for clinical stage II/III esophageal carcinoma (JCOG 0604)

Makoto Tahara, Nozomu Fuse, Junki Mizusawa, Akihiro Sato, Keiji Nihei, Keisuke Kanato, Ken Kato, Kentaro Yamazaki, Kei Muro, Hiromasa Takaishi, Narikazu Boku, Atsushi Ohtsu

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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/m2/day on days 1-14, and cisplatin at 75 mg/m2 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/m2/day). Considering treatment compliance, the recommended dose was determined to be S-1 60 mg/m2/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.

Original languageEnglish
JournalCancer Science
DOIs
Publication statusAccepted/In press - 2015

Fingerprint

Chemoradiotherapy
Cisplatin
Carcinoma
Radiation Dosage
Drug Therapy
Febrile Neutropenia
Survival
Maximum Tolerated Dose
Hyponatremia
Leukopenia
Anorexia
Esophageal Neoplasms
Neutropenia
Thrombocytopenia
Disease-Free Survival
Registries
Anemia
Thorax
Clinical Trials
Confidence Intervals

Keywords

  • Chemoradiotherapy
  • Cisplatin
  • Esophageal carcinoma
  • S-1
  • Stage II/III

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase I/II trial of chemoradiotherapy with concurrent S-1 and cisplatin for clinical stage II/III esophageal carcinoma (JCOG 0604). / Tahara, Makoto; Fuse, Nozomu; Mizusawa, Junki; Sato, Akihiro; Nihei, Keiji; Kanato, Keisuke; Kato, Ken; Yamazaki, Kentaro; Muro, Kei; Takaishi, Hiromasa; Boku, Narikazu; Ohtsu, Atsushi.

In: Cancer Science, 2015.

Research output: Contribution to journalArticle

Tahara, Makoto ; Fuse, Nozomu ; Mizusawa, Junki ; Sato, Akihiro ; Nihei, Keiji ; Kanato, Keisuke ; Kato, Ken ; Yamazaki, Kentaro ; Muro, Kei ; Takaishi, Hiromasa ; Boku, Narikazu ; Ohtsu, Atsushi. / Phase I/II trial of chemoradiotherapy with concurrent S-1 and cisplatin for clinical stage II/III esophageal carcinoma (JCOG 0604). In: Cancer Science. 2015.
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T1 - Phase I/II trial of chemoradiotherapy with concurrent S-1 and cisplatin for clinical stage II/III esophageal carcinoma (JCOG 0604)

AU - Tahara, Makoto

AU - Fuse, Nozomu

AU - Mizusawa, Junki

AU - Sato, Akihiro

AU - Nihei, Keiji

AU - Kanato, Keisuke

AU - Kato, Ken

AU - Yamazaki, Kentaro

AU - Muro, Kei

AU - Takaishi, Hiromasa

AU - Boku, Narikazu

AU - Ohtsu, Atsushi

PY - 2015

Y1 - 2015

N2 - 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/m2/day on days 1-14, and cisplatin at 75 mg/m2 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/m2/day). Considering treatment compliance, the recommended dose was determined to be S-1 60 mg/m2/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.

AB - 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/m2/day on days 1-14, and cisplatin at 75 mg/m2 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/m2/day). Considering treatment compliance, the recommended dose was determined to be S-1 60 mg/m2/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.

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KW - Cisplatin

KW - Esophageal carcinoma

KW - S-1

KW - Stage II/III

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