title: Outcome in advanced non-small cell lung cancer patients with successful rechallenge after recovery from epidermal growth factor receptor tyrosine kinase inhibitor-induced interstitial lung disease.
abstract: Several non-small cell lung cancer (NSCLC) cases of successful rechallenge with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) after recovery from gefitinib or erlotinib-induced interstitial lung disease (ILD) have been reported, but it is not clear whether the rechallenge affects the outcome.
  
  
  
  We retrospectively evaluated the difference in the outcome between advanced NCLC patients with active EGFR mutations who received EGFR-TKI rechallenge after recovery from EGFR-TKI-induced ILD and those who did not.
  
  
  
  EGFR-TKI-induced ILD occurred in 11 (10%) of 110 patients receiving gefitinib, five (7%) of 73 patients receiving erlotinib and one (8%) of 13 patients receiving afatinib. Diffuse alveolar damage pattern ILD was observed in six cases, four of which had chemotherapy-related death. Five of 13 patients who had recovered from ILD received EGFR-TKI rechallenge with concurrent oral administration of prednisolone 0.5 mg/kg after the strict informed consent of the risk for the recurrence of severe ILD. All of the five patients achieved a partial response. The median overall survival from the occurrence of EGFR-TKI-induced ILD was longer in patients with EGFR-TKI rechallenge than that in patients without (15.5 vs. 3.5 months, p = 0.029). The adverse events of EGFR-TKI rechallenge were tolerable, but one case receiving EGFR-TKI rechallenge with the suspected drug exhibited the recurrence of grade 3 ILD after the discontinuation of prednisolone.
  
  
  
  EGFR-TKI rechallenge with concurrent prednisolone therapy might be salvage therapy in advanced NSCLC patients with active EGFR mutations after recovery from EGFR-TKI-induced ILD.
authors.affiliation: Department of Respiratory Medicine, Kumamoto Regional Medical Center, 5-16-10 hon-jo, Kumamoto, 860-0811, Japan. kskkswbr@krmc.or.jp.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kashiwabara
authors.affiliation: Department of Respiratory Medicine, Kumamoto Regional Medical Center, 5-16-10 hon-jo, Kumamoto, 860-0811, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Semba
authors.affiliation: Department of Respiratory Medicine, Kumamoto Regional Medical Center, 5-16-10 hon-jo, Kumamoto, 860-0811, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Fujii
authors.affiliation: Department of Respiratory Medicine, Kumamoto Regional Medical Center, 5-16-10 hon-jo, Kumamoto, 860-0811, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Tsumura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D000069347:Erlotinib Hydrochloride / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D000077156:Gefitinib; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000139:chemically induced* / Q000188:drug therapy / Q000235:genetics; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011239:Prednisolone / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods; D016019:Survival Analysis; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D011239:Prednisolone; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: Corticosteroid; Drug-induced interstitial lung disease; Erlotinib; Gefitinib; Rechallenge