title: Early pneumothorax as a feature of response to crizotinib therapy in a patient with ALK rearranged lung adenocarcinoma.
abstract: BACKGROUND
  Single arm phase 1 and 2 studies on Crizotinib in ALK-positive patients so far have shown rapid and durable responses. Spontaneous pneumothoraces as a result of response to anti-cancer therapy are rare in oncology but have been documented in a number of tumour types including lung cancer. This includes cytotoxic chemotherapy as well as molecular targeted agents such as gefitinib and Bevacizumab. These often require chest drain insertion or surgical intervention with associated morbidity and mortality. They have also been associated with response to treatment. This is the first report we are aware of documenting pneumothorax as response to crizotinib therapy.
  
  
  METHODS
  A 48-year-old Caucasian male presented with a Stage IV, TTF1 positive, EGFR wild-type adenocarcinoma of the lung. He received first line chemotherapy with three cycles of cisplatin-pemetrexed chemotherapy with a differential response, and then second-line erlotinib for two months before further radiological evidence of disease progression. Further analysis of his diagnostic specimen identified an ALK rearrangement by fluorescence in situ hybridization (FISH). He was commenced on crizotinib therapy 250 mg orally twice daily. At his 4-week assessment he had a chest radiograph that identified a large left-sided pneumothorax with disease response evident on the right. Chest CT confirmed a 50% left-sided pneumothorax on a background of overall disease response. A chest tube was inserted with complete resolution of the pneumothorax that did not recur following its removal.
  
  
  CONCLUSIONS
  Our case demonstrates this potential complication of crizotinib therapy and we therefore recommend that pneumothorax be considered in patients on crizotinib presenting with high lung metastatic burden and with worsening dyspnoea.
authors.forename: Spyridon
authors.initials: S
authors.lastname: Gennatas
authors.forename: Susana J
authors.initials: SJ
authors.lastname: Stanway
authors.forename: Robert
authors.initials: R
authors.lastname: Thomas
authors.forename: Toon
authors.initials: T
authors.lastname: Min
authors.forename: Riyaz
authors.initials: R
authors.lastname: Shah
authors.forename: Mary E R
authors.initials: ME
authors.lastname: O'Brien
authors.forename: Sanjay
authors.initials: S
authors.lastname: Popat
mesh_terms: D000230:Adenocarcinoma / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000077547:Crizotinib; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011030:Pneumothorax / Q000139:chemically induced* / Q000175:diagnosis; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011720:Pyrazoles / Q000009:adverse effects*; D011725:Pyridines / Q000009:adverse effects*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*
chemical_list: D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases