Noninfectious pneumonitis after everolimus therapy for advanced renal cell carcinoma Journal Article
| Authors: | White, D. A.; Camus, P.; Endo, M.; Escudier, B.; Calvo, E.; Akaza, H.; Uemura, H.; Kpamegan, E.; Kay, A.; Robson, M.; Ravaud, A.; Motzer, R. J. |
| Article Title: | Noninfectious pneumonitis after everolimus therapy for advanced renal cell carcinoma |
| Abstract: | 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). |
| Keywords: | adult; cancer survival; controlled study; aged; aged, 80 and over; middle aged; major clinical study; clinical trial; sorafenib; placebo; sunitinib; advanced cancer; drug dose reduction; drug withdrawal; side effect; treatment duration; follow up; prospective study; progression free survival; computer assisted tomography; controlled clinical trial; lung toxicity; randomized controlled trial; tomography, x-ray computed; kidney carcinoma; kidney neoplasms; pneumonia; hospitalization; severity of illness index; kidney tumor; carcinoma, renal cell; chemically induced disorder; drug derivative; radiography; bronchoscopy; thorax radiography; corticosteroid; drug treatment failure; lung function test; kidney metastasis; everolimus; rapamycin; sirolimus; immunosuppressive agents; immunosuppressive agent; transbronchial biopsy; rad001; respiratory function tests; mtor (mammalian target of rapamycin) inhibitors; corticosteroid therapy; noninfectious pneumonitis; adrenal cortex hormones |
| Journal Title: | American Journal of Respiratory and Critical Care Medicine |
| Volume: | 182 |
| Issue: | 3 |
| ISSN: | 1073-449X |
| Publisher: | American Thoracic Society |
| Date Published: | 2010-08-01 |
| Start Page: | 396 |
| End Page: | 403 |
| Language: | English |
| DOI: | 10.1164/rccm.200911-1720OC |
| PUBMED: | 20194812 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 3" - "Export Date: 20 April 2011" - "CODEN: AJCME" - "Source: Scopus" |
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