title: Concurrent cetuximab and radiotherapy after docetaxel-cisplatin induction chemotherapy in stage III NSCLC: satellite--a phase II study from the Swedish Lung Cancer Study Group.
abstract: BACKGROUND
  Several attempts to increase the locoregional control in locally advanced lung cancer including concurrent chemotherapy, accelerated fractionation and dose escalation have been made during the last years. As the EGFR directed antibody cetuximab has shown activity concurrent with radiotherapy in squamous cell carcinoma of the head and neck, as well as in stage IV NSCLC combined with chemotherapy, we wanted to investigate radiotherapy with concurrent cetuximab in locally advanced NSCLC, a tumour type often over expressing the EGF-receptor.
  
  
  METHODS
  Between February 2006 and August 2007 75 patients in stage III NSCLC with good performance status (PS 0 or 1) and adequate lung function (FEV1>1.0) were enrolled in this phase II study at eight institutions. Treatment consisted of 2 cycles of induction chemotherapy, docetaxel 75 mg/m² and cisplatin 75 mg/m² with 3 weeks interval. An initial dose of cetuximab 400 mg/m² was given before start of 3D-CRT to 68 Gy with 2 Gy per fraction in 7 weeks concurrent with weekly cetuximab 250 mg/m². TOXICITY was scored weekly during radiotherapy (CTC 3.0), and after treatment the patients were followed every third month with CT-scans, toxicity scoring and QLQ.
  
  
  RESULTS
  Seventy-one patients were eligible for analysis as four were incorrectly enrolled.
  
  
  RESULTS
  adenocarcinoma 49%, squamous cell carcinoma 39% and other NSCLC 12%. The majority had PS 0 (62.5%), median age 62.2 (42-81), 50% were women and 37% had a pre-treatment weight loss>5%.
  
  
  RESULTS
  esophagitis grade 1-2: 72%; grade 3: 1.4%. Hypersensitivity reactions grade 3-4: 5.6%. Febrile neutropenia grade 3-4: 15.4%. Skin reactions grade 1-2: 74%; grade 3: 4.2%. Diarrhoea grade 1-2: 38%; grade 3: 11.3%. Pneumonitis grade 1-2: 26.8%; grade 3: 4.2%; grade 5: 1.4%. The median follow-up was 39 months for patients alive and the median survival was 17 months with a 1-, 2- and 3-year OS of 66%, 37% and 29% respectively. Until now local or regional failure has occurred in 20 patients and 22 patients have developed distant metastases. Weight loss, PS and stage were predictive for survival in univariate as well as in multivariate analysis.
  
  
  CONCLUSIONS
  Induction chemotherapy followed by concurrent cetuximab and RT to 68 Gy is clearly feasible with promising survival. TOXICITY, e.g. pneumonitis and esophagitis is low compared to most schedules with concurrent chemotherapy. This treatment strategy should be evaluated in a randomised manner vs. concurrent chemoradiotherapy to find out if it is a valid treatment option.
authors.affiliation: Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sweden. andreas.hallqvist@oncology.gu.se
authors.forename: A
authors.initials: A
authors.lastname: Hallqvist
authors.forename: G
authors.initials: G
authors.lastname: Wagenius
authors.forename: H
authors.initials: H
authors.lastname: Rylander
authors.forename: O
authors.initials: O
authors.lastname: Brodin
authors.forename: E
authors.initials: E
authors.lastname: Holmberg
authors.forename: B
authors.initials: B
authors.lastname: Lödén
authors.forename: S-B
authors.initials: SB
authors.lastname: Ewers
authors.forename: S
authors.initials: S
authors.lastname: Bergström
authors.forename: G
authors.initials: G
authors.lastname: Wichardt-Johansson
authors.forename: K
authors.initials: K
authors.lastname: Nilsson
authors.forename: L
authors.initials: L
authors.lastname: Ekberg
authors.forename: C
authors.initials: C
authors.lastname: Sederholm
authors.forename: J
authors.initials: J
authors.lastname: Nyman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use* / Q000633:toxicity; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D000068818:Cetuximab; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use; D003131:Combined Modality Therapy; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010349:Patient Compliance; D011788:Quality of Life; D012008:Recurrence; D016019:Survival Analysis; D013548:Sweden; D043823:Taxoids / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D000068818:Cetuximab; D002945:Cisplatin