title: Patterns of interstitial lung disease during everolimus treatment in patients with metastatic renal cell carcinoma.
abstract: OBJECTIVE
  To elucidate the patterns of interstitial lung disease during everolimus treatment in patients with metastatic renal cell carcinoma, we reviewed seven cases of everolimus-induced interstitial lung disease.
  
  
  METHODS
  Seven patients with metastatic renal cell carcinoma, which continued to progress despite treatment with sunitinib or sorafenib, developed interstitial lung disease after treatment with everolimus.
  
  
  RESULTS
  Chest X-ray demonstrated diffuse infiltrates in lung fields, and chest computed tomography showed bilateral reticular and ground-glass opacities. Serum levels of lactate dehydrogenase (7/7), C-reactive protein (6/7), pulmonary surfactant associated protein D (1/7) and Krebs von den Lungen 6 (5/7) were elevated. The bronchoalveolar lavage fluid obtained from four patients with Grade 3 interstitial lung disease showed lymphocytosis. The transbronchial lung biopsy specimens showed interstitial lymphocytic infiltration and septal thickening of alveolar walls. In two cases with mild interstitial lung disease, the everolimus therapy was successfully continued. In four cases with Grade 3 interstitial lung disease, the drug was discontinued and steroid therapy was initiated. Pulmonary symptoms and radiological abnormalities resolved within 2 months.
  
  
  CONCLUSIONS
  Serum Krebs von den Lungen 6 was elevated compared with baseline in all cases with interstitial lung disease. Some patients who developed mild interstitial lung disease during everolimus treatment could continue to receive the treatment. Even when severe interstitial lung disease developed, withdrawal of the drug and short-term use of high-dose steroids resulted in rapid recovery. Prompt recognition of interstitial lung disease exacerbation as well as exclusion of progressive disease or infection is of primary importance.
authors.affiliation: Department of Urology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan. mizunor@z7.keio.jp
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Mizuno
authors.forename: Koichiro
authors.initials: K
authors.lastname: Asano
authors.forename: Shuji
authors.initials: S
authors.lastname: Mikami
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Nagata
authors.forename: Gou
authors.initials: G
authors.lastname: Kaneko
authors.forename: Mototsugu
authors.initials: M
authors.lastname: Oya
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001706:Biopsy; D001992:Bronchoalveolar Lavage Fluid; D002097:C-Reactive Protein / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D003937:Diagnosis, Differential; D018450:Disease Progression; D004334:Drug Administration Schedule; D000068338:Everolimus; D005260:Female; D006801:Humans; D007564:Japan; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008168:Lung / Q000000981:diagnostic imaging / Q000473:pathology*; D017563:Lung Diseases, Interstitial / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000097:blood; D012720:Severity of Illness Index; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D014057:Tomography, X-Ray Computed
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; C060192:MUC1 protein, human; D018396:Mucin-1; D011663:Pulmonary Surfactants; D002097:C-Reactive Protein; D000068338:Everolimus; D007770:L-Lactate Dehydrogenase; D020123:Sirolimus