PMID- 20194812 OWN - NLM STAT- MEDLINE DCOM- 20100914 LR - 20161125 IS - 1535-4970 (Electronic) IS - 1073-449X (Linking) VI - 182 IP - 3 DP - 2010 Aug 1 TI - Noninfectious pneumonitis after everolimus therapy for advanced renal cell carcinoma. PG - 396-403 LID - 10.1164/rccm.200911-1720OC [doi] AB - RATIONALE: Noninfectious pneumonitis is a known class effect of mammalian target of rapamycin (mTOR) inhibitors. OBJECTIVES: To assess the incidence, radiographic patterns, management, and outcome of pneumonitis in patients with advanced renal cell carcinoma receiving everolimus. METHODS: Clinical study data from 416 patients, randomized to receive everolimus versus placebo, were analyzed for adverse events of pneumonitis. Radiographic studies performed every 8 weeks were subject to a prospective, independent, blinded central review for the presence of findings indicative of pneumonitis. MEASUREMENTS AND MAIN RESULTS: Of 274 patients receiving everolimus, clinical pneumonitis was suspected for 37 patients (13.5%) (none with placebo). Nine cases (3.3%) were grade 1 (asymptomatic), 18 (6.6%) were grade 2 (not interfering with daily living), and 10 (3.6%) were grade 3 (interfering with daily living or oxygen indicated). No grade 4 (life-threatening) pneumonitis was observed. Of the 10 patients with grade 3 pneumonitis, 5 had baseline radiological evidence of pneumonitis before everolimus therapy. Twenty of the 37 cases (54.0%) were reversible within the follow-up period; resolution followed dose reduction for 20 patients and treatment discontinuation in 10 patients. Corticosteroid therapy was initiated in 16 cases. Dedicated radiological review of available serial radiographic studies (245 patients receiving everolimus and 132 receiving placebo) found a higher percentage of new radiographic findings even in patients without a diagnosis of clinical pneumonitis who were receiving everolimus versus placebo (38.9 vs. 15.2%). CONCLUSIONS: Early recognition, prompt intervention, and a conservative approach are important in managing the risk associated with noninfectious pneumonitis in association with everolimus. Clinical trial registered with www.clinicaltrials.gov (NCT 00410124). FAU - White, Dorothy A AU - White DA AD - Memorial Sloan-Kettering Cancer Center, Pulmonary Medicine, New York, NY 10021, USA. whited@mskcc.org FAU - Camus, Philippe AU - Camus P FAU - Endo, Masahiro AU - Endo M FAU - Escudier, Bernard AU - Escudier B FAU - Calvo, Emiliano AU - Calvo E FAU - Akaza, Hideyuki AU - Akaza H FAU - Uemura, Hirotsugu AU - Uemura H FAU - Kpamegan, Euloge AU - Kpamegan E FAU - Kay, Andrea AU - Kay A FAU - Robson, Matthew AU - Robson M FAU - Ravaud, Alain AU - Ravaud A FAU - Motzer, Robert J AU - Motzer RJ LA - eng SI - ClinicalTrials.gov/NCT00410124 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20100301 PL - United States TA - Am J Respir Crit Care Med JT - American journal of respiratory and critical care medicine JID - 9421642 RN - 0 (Adrenal Cortex Hormones) RN - 0 (Immunosuppressive Agents) RN - 9HW64Q8G6G (Everolimus) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Adrenal Cortex Hormones/therapeutic use MH - Adult MH - Aged MH - Aged, 80 and over MH - Carcinoma, Renal Cell/*drug therapy MH - Everolimus MH - Female MH - Humans MH - Immunosuppressive Agents/administration & dosage/*adverse effects MH - Kidney Neoplasms/*drug therapy MH - Male MH - Middle Aged MH - Pneumonia/*chemically induced/diagnostic imaging/drug therapy MH - Respiratory Function Tests MH - Severity of Illness Index MH - Sirolimus/administration & dosage/adverse effects/*analogs & derivatives MH - Tomography, X-Ray Computed EDAT- 2010/03/03 06:00 MHDA- 2010/09/16 06:00 CRDT- 2010/03/03 06:00 PHST- 2010/03/03 06:00 [entrez] PHST- 2010/03/03 06:00 [pubmed] PHST- 2010/09/16 06:00 [medline] AID - 200911-1720OC [pii] AID - 10.1164/rccm.200911-1720OC [doi] PST - ppublish SO - Am J Respir Crit Care Med. 2010 Aug 1;182(3):396-403. doi: 10.1164/rccm.200911-1720OC. Epub 2010 Mar 1.