title: Phase I clinical trial of the anti-EGFR monoclonal antibody nimotuzumab with concurrent external thoracic radiotherapy in Canadian patients diagnosed with stage IIb, III or IV non-small cell lung cancer unsuitable for radical therapy.
abstract: OBJECTIVE
  Many patients with non-small cell lung cancer (NSCLC) are eligible only for palliative radiation (RT) at presentation. This study was designed to assess the feasibility of adding the anti-EGFR monoclonal antibody nimotuzumab to palliative thoracic RT.
  
  
  METHODS
  Patients with stage IIB, III or IV NSCLC considered unsuitable for radical radiation or chemo-radiation received nimotuzumab weekly 8× (100, 200 or 400 mg) with radiation (30 or 36 Gy in 3 Gy fractions). If response or disease stability was observed, nimotuzumab was continued every other week starting from week 10 until progression or toxicity.
  
  
  RESULTS
  Eighteen patients were enrolled: 6 at 100 mg, 7 at 200 mg, 5 at 400 mg nimotuzumab. Patient characteristics included median age 69 years, 11 males, 17 smokers, 17 Caucasians, stage IIIA/IIIB/IV 2/7/9, 5 Eastern Cooperative Oncology Group performance status (PS) 2; 9 adenocarcinoma. The most commonly reported adverse events were fatigue, anorexia, chills, pain and hypophosphatemia (grades 1 to 2 in most patients). No severe skin or allergic toxicity was noted. No dose-limiting toxicity was encountered. Objective response rate and disease control rate inside the radiation field were 66 and 94.0%, respectively.
  
  
  CONCLUSIONS
  Nimotuzumab administered concurrently with palliative thoracic radiation is well tolerated at each of the three doses investigated in NSCLC patients unsuitable for radical treatment. The low toxicity and absence of rash make this combination therapeutically attractive for frail patients with other co-morbidities and poor performance status. These results support further testing of this regimen in the phase II setting.
authors.affiliation: Translational Research Laboratory, Tom Baker Cancer Centre, University of Calgary, 1331, 29th St NW, Calgary, Alberta T2N 4N2, Canada. gwyn.bebb@albertahealthservices.ca
authors.forename: Gwyn
authors.initials: G
authors.lastname: Bebb
authors.forename: Colum
authors.initials: C
authors.lastname: Smith
authors.forename: Stewart
authors.initials: S
authors.lastname: Rorke
authors.forename: William
authors.initials: W
authors.lastname: Boland
authors.forename: Leonardo
authors.initials: L
authors.lastname: Nicacio
authors.forename: Ryan
authors.initials: R
authors.lastname: Sukhoo
authors.forename: Anthony
authors.initials: A
authors.lastname: Brade
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002170:Canada; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D009367:Neoplasm Staging; D010166:Palliative Care / Q000379:methods; D011829:Radiation Dosage
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C501466:nimotuzumab; D066246:ErbB Receptors