A phase I dose escalation study of Nimotuzumab in combination with concurrent chemoradiation for patients with locally advanced squamous cell carcinoma of esophagus

Invest New Drugs. 2012 Aug;30(4):1585-90. doi: 10.1007/s10637-011-9735-0. Epub 2011 Sep 8.

Abstract

Nimotuzumab (h-R3) is a humanized anti-epidermal growth factor receptor monoclonal antibody. We conducted a phase I study to assess the safety, tolerance, maximal tolerance dose (MTD) and efficacy of h-R3 in combination with concurrent chemoradiation in patient with locally advanced esophageal carcinoma. Patients with locally advanced squamous cell carcinoma of esophagus were eligible. A total dose of 61.2 Gy was delivered by conventional fractionation. Chemotherapy was concurrently administered with irradiation every 4 weeks with PF regimen (cis-platinum of 25 mg/m(2)/d, d1-3; 5-Fu of 1,800 mg/m(2), intravenously infusion in 72 h) for 4 cycles. h-R3 was administrated weekly during irradiation for 6 weeks. h-R3 dose escalation started with 100 mg/week, and followed by 200 mg/week and 400 mg/week. Three patients were enrolled in of each dose cohort. 11 patients were enrolled in the trial with 3, 4 and 4 in 100 mg/week, 200 mg/week and 400 mg/week cohort, respectively. 2 patients in 200 mg/week and 400 mg/week cohort were withdrawn due to patients' own decisions. No dose limiting toxicity was observed. Grade 3-4 of esophagitis, Grade 3 of leucocytopenia and neutrocytopenia occurred in 18% (2/11), 18% (2/11) and 9% (1/11) of patients, respectively. For nimotuzumab-related toxicity only one patient experienced Grade 1 skin rash, and no Grade ≥ 3 of toxicity was noticed. In 9 patients, who completed planned treatments, 6-month and 1-year overall survival were 78% and 67%, respectively, and 1 year local progression-free survival, 100%. h-R3 of 400 mg/week administered concurrently with chemoradiation was well-tolerant. MTD has not been reached yet.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / radiotherapy*
  • Combined Modality Therapy
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / radiotherapy*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Radiotherapy Dosage
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • nimotuzumab