title: Drug-related pneumonitis in patients with advanced renal cell carcinoma treated with temsirolimus.
abstract: OBJECTIVE
  Pneumonitis has occurred in patients treated with inhibitors of the mammalian target of rapamycin (mTOR). In a phase III study of patients with previously untreated, poor-prognosis, advanced renal cell carcinoma (ARCC), the mTOR inhibitor temsirolimus improved survival compared with interferon. We performed a retrospective, independent, blinded radiographic review of chest computed tomography (CT) images of patients in this study to characterize temsirolimus-related pneumonitis.
  
  
  METHODS
  Patients were treated with intravenous temsirolimus 25 mg once weekly or subcutaneous interferon alfa 3 million units, with an increase to 18 million units, thrice weekly. Drug-related pneumonitis was identified based on sequential chest CT images, required every 8 weeks, showing changes consistent with pneumonitis and not pneumonia (infection) or disease progression as correlated with clinical data. Cumulative probability of drug-related pneumonitis was estimated using the Kaplan-Meier method.
  
  
  RESULTS
  Eight (6%) of 138 and 52 (29%) of 178 evaluable patients on interferon and temsirolimus treatment, respectively, developed radiographically identified drug-related pneumonitis. Time to onset of pneumonitis was significantly shorter on the temsirolimus arm than on the interferon arm (log-rank P < .001). Estimated cumulative probability of pneumonitis at 8 and 16 weeks from first dose was 21% and 31%, respectively, on the temsirolimus arm and 6% and 8%, respectively, on the interferon arm. Respiratory symptoms were observed around time of onset of radiographically diagnosed temsirolimus-related pneumonitis in 16 (31%) of 52 patients.
  
  
  CONCLUSIONS
  Patients with ARCC receiving temsirolimus should be monitored closely for development of pneumonitis, and their management should be altered if clinical symptoms appear.
authors: Sant Pau Hospital, Padre Claret 167, Barcelona, 08025 Spain. JMaroto@santpau.cat
authors: Jose Pablo
authors: JP
authors: Maroto
authors: Gary
authors: G
authors: Hudes
authors: Janice P
authors: JP
authors: Dutcher
authors: Theodore F
authors: TF
authors: Logan
authors: Charles S
authors: CS
authors: White
authors: Mizue
authors: M
authors: Krygowski
authors: Maria
authors: M
authors: Cincotta
authors: Mark
authors: M
authors: Shapiro
authors: Ignacio
authors: I
authors: Duran
authors: Anna
authors: A
authors: Berkenblit
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D002292:Carcinoma, Renal Cell / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D015994:Incidence; D016898:Interferon-alpha / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D011014:Pneumonia / Q000000981:diagnostic imaging / Q000453:epidemiology*; D016032:Randomized Controlled Trials as Topic; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D014057:Tomography, X-Ray Computed
chemical_list: D000970:Antineoplastic Agents; D016898:Interferon-alpha; C401859:temsirolimus; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus