Open AccessNimotuzumab combined with concurrent chemoradiotherapy in Japanese patients with esophageal cancer: A phase I study
Author(s) -
Kato Ken,
Ura Takashi,
Koizumi Wasaburo,
Iwasa Satoru,
Katada Chikatoshi,
Azuma Mizutomo,
Ishikura Satoshi,
Nakao Yoshinori,
Onuma Hiroshi,
Muro Kei
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13481
Subject(s) - medicine , nimotuzumab , esophageal cancer , gastroenterology , neutropenia , tolerability , mucositis , leukopenia , chemotherapy , chemoradiotherapy , febrile neutropenia , phases of clinical research , fluorouracil , cancer , surgery , oncology , adverse effect , epidermal growth factor receptor
Nimotuzumab is a humanized anti‐epidermal growth factor receptor IgG1 monoclonal antibody. This phase I study assessed the tolerability, safety, efficacy, and pharmacokinetics of nimotuzumab in combination with chemoradiotherapy in Japanese patients with esophageal cancer. Patients with stage II , III , and IV esophageal cancer were enrolled. Patients were planned to receive nimotuzumab (level 1: 200 mg/wk for 25 weeks; or level 2: 400 mg/wk in the chemoradiation period, 400 mg biweekly in an additional chemotherapy period [8 weeks after the chemoradiation period] and a maintenance therapy period [after chemotherapy to 25 weeks]) combined with cisplatin (75 mg/m 2 on day 1) and fluorouracil (1000 mg/m 2 on days 1‐4) in the chemoradiation and additional chemotherapy periods. Radiotherapy was given concurrently at 50.4 Gy. A total of 10 patients were enrolled in level 1. Dose‐limiting toxicities were observed in 2 patients (grade 3 infection and renal disorder). Maximum‐tolerated dose was estimated to be at least 200 mg/wk and the dose was not escalated to level 2. The most common grade ≥3 toxicities were lymphopenia (90%), leukopenia (60%), neutropenia (50%), and febrile neutropenia, decreased appetite, hyponatremia, and radiation esophagitis (30% each). Neither treatment‐related death nor grade ≥3 skin toxicity was observed in any patient. Complete response rate was 50%. Progression‐free survival was 13.9 months. One‐ and 3‐year survival rates were 75% and 37.5%, respectively. Immunogenicity was not reported in any patient. Nimotuzumab in combination with concurrent chemoradiotherapy was tolerable and effective for Japanese patients with esophageal cancer.