title: Tracheoesophageal fistula formation in patients with lung cancer treated with chemoradiation and bevacizumab.
abstract: PURPOSE Tracheoesophageal fistulae are rare complications of thoracic cancers and their treatments. Novel antiangiogenic agents in cancer treatment such as bevacizumab potentially impact wound healing and may contribute to tracheoesophageal fistula development. PATIENTS AND METHODS We conducted two independent phase II clinical trials in small-cell lung cancer and non-small-cell lung cancer using bevacizumab in combination with chemotherapy and radiation. Both trials were intended to assess preliminary efficacy and safety outcomes. Results For the limited-stage small-cell lung cancer trial, 29 patients were enrolled beginning April 2006, and closed early due to toxicity in March 2007 (14-month median follow-up). The locally advanced, non-small-cell lung cancer trial opened with enrollment limited to five patients in February 2007, and closed early due to safety in December 2007. In each trial, we observed tracheoesophageal fistulae development and related morbidity and mortality, prompting early trial closures, US Food and Drug Administration warnings, and a change in bevacizumab labeling. CONCLUSION The current data from the final reports from these two trials suggest bevacizumab and chemoradiotherapy are associated with a relatively high incidence of tracheoesophageal fistulae formation in both small-cell lung cancer and non-small-cell lung cancer settings. Strategies to safely incorporate novel antiangiogenic agents into combined-modality therapy in lung cancer are needed.
authors.affiliation: Sarah Cannon Research Institute, 250 25th Avenue North, Suite 110, Nashville, TN 37203, USA. dspigel@tnonc.com
authors.forename: David R
authors.initials: DR
authors.lastname: Spigel
authors.forename: John D
authors.initials: JD
authors.lastname: Hainsworth
authors.forename: Denise A
authors.initials: DA
authors.lastname: Yardley
authors.forename: Eric
authors.initials: E
authors.lastname: Raefsky
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Patton
authors.forename: Nancy
authors.initials: N
authors.lastname: Peacock
authors.forename: Cindy
authors.initials: C
authors.lastname: Farley
authors.forename: Howard A
authors.initials: HA
authors.lastname: Burris
authors.forename: F Anthony
authors.initials: FA
authors.lastname: Greco
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects*; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002289:Carcinoma, Non-Small-Cell Lung / Q000628:therapy*; D018288:Carcinoma, Small Cell / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D014138:Tracheoesophageal Fistula / Q000209:etiology*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab