title: Incorporating bevacizumab and erlotinib in the combined-modality treatment of stage III non-small-cell lung cancer: results of a phase I/II trial.
abstract: OBJECTIVE
  Bevacizumab and erlotinib have been shown to improve survival in stage IV non-small-cell lung cancer (NSCLC). This phase I/II trial was designed to incorporate these agents with induction and concurrent chemoradiotherapy in stage III NSCLC.
  
  
  METHODS
  Patients received induction chemotherapy (carboplatin area under the curve [AUC] 6, paclitaxel 225 mg/m(2), and bevacizumab 15 mg/kg on days 1 and 22) followed by concurrent chemotherapy (carboplatin AUC 2 and paclitaxel 45 mg/m(2) weekly with bevacizumab 10 mg/kg every other week for four doses) and thoracic conformal radiation therapy (TCRT) to 74 Gy. In the phase I portion, cohort 1 received no erlotinib, whereas cohorts 2 and 3 received erlotinib at 100 and 150 mg, respectively, Tuesday through Friday, during TCRT. Consolidation therapy with erlotinib (150 mg daily) and bevacizumab (15 mg/kg every 3 weeks) was planned 3 to 6 weeks later for six cycles.
  
  
  RESULTS
  Forty-five eligible patients were enrolled. The objective response rates to induction and overall treatment were 39% (95% CI, 24% to 55%) and 60% (95% CI, 44% to 75%), respectively. The median progression-free and overall survival times were 10.2 months (95% CI, 8.4 to 18.3 months) and 18.4 months (95% CI, 13.4 to 31.7 months), respectively. The principal toxicity was esophagitis (29% grade 3 or 4 esophagitis, with one patient with grade 3 tracheoesophageal fistula), which was often prolonged. Consolidation therapy with bevacizumab and erlotinib was not feasible.
  
  
  CONCLUSIONS
  The use of bevacizumab and erlotinib as administered in this trial is not recommended given the lack of an efficacy signal and the substantial risk of esophageal toxicity.
authors.affiliation: UPMC Cancer Pavilion, 5150 Centre Avenue, 5th Floor, Pittsburgh, PA 15232, USA. socinskima@upmc.edu
authors.forename: Mark A
authors.initials: MA
authors.lastname: Socinski
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Stinchcombe
authors.forename: Dominic T
authors.initials: DT
authors.lastname: Moore
authors.forename: Scott N
authors.initials: SN
authors.lastname: Gettinger
authors.forename: Roy H
authors.initials: RH
authors.lastname: Decker
authors.forename: W Jeffrey
authors.initials: WJ
authors.lastname: Petty
authors.forename: A William
authors.initials: AW
authors.lastname: Blackstock
authors.forename: Garry
authors.initials: G
authors.lastname: Schwartz
authors.forename: Scott
authors.initials: S
authors.lastname: Lankford
authors.forename: Amir
authors.initials: A
authors.lastname: Khandani
authors.forename: David E
authors.initials: DE
authors.lastname: Morris
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D000069347:Erlotinib Hydrochloride; D004941:Esophagitis / Q000139:chemically induced*; D004947:Esophagus / Q000187:drug effects*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D020266:Radiotherapy, Conformal; D012074:Remission Induction; D014138:Tracheoesophageal Fistula / Q000139:chemically induced; D017211:Treatment Failure
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D011799:Quinazolines; D000068258:Bevacizumab; D000069347:Erlotinib Hydrochloride