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Medline ® Abstract for Reference 121

of 'Pulmonary toxicity associated with antineoplastic therapy: Molecularly targeted agents'

121
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Characterization of pneumonitis in patients with advanced non-small cell lung cancer treated with everolimus (RAD001).
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White DA, Schwartz LH, Dimitrijevic S, Scala LD, Hayes W, Gross SH
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J Thorac Oncol. 2009;4(11):1357.
 
PURPOSE: To assess the incidence and radiographic and clinical presentation of pneumonitis associated with the mammalian target of rapamycin inhibitor everolimus in patients with advanced non-small cell lung cancer.
PATIENTS AND METHODS: A retrospective, centralized review of serial computed tomography scans and corresponding clinical data from patients with advanced non-small cell lung cancer treated with 10-mg oral once daily everolimus monotherapy in a phase II clinical study was conducted. Serial chest CT scans underwent a consensus read by two radiologists for presence of pneumonitis. These cases were then reviewed with corresponding clinical data by a pulmonologist to assess the suspected causality to everolimus and outcome.
RESULTS: Twenty-four of 64 patients reviewed were found to have radiographic evidence of pneumonitis. In 16 of these 24 patients, pneumonitis was suspected as either possibly (12) or probably (4) related to everolimus. The most common radiographic manifestations were focal areas of consolidation at the lung bases or ground-glass opacities. Pneumonitis evaluated with Common Terminology Criteria for Adverse Events (version 3) was grade 1 or 2 in 12 of 16 suspected cases, with 4 patients experiencing higher grades. In most of the patients, pneumonitis remained at the same or lower grade without discontinuation of therapy. Patients with evidence of interstitial lung disease at baseline had an increased risk of Common Terminology Criteria for Adverse Events grade more than or equal to 3 pneumonitis.
CONCLUSION: Within the limitation of this retrospective study, results suggest that a mostly low-grade pneumonitis with a possible or probable relationship to everolimus was relatively frequent, occurring in 25% of evaluated patients. These results suggest a need for monitoring of pulmonary adverse events and the development of guidelines for managing pneumonitis in future studies with everolimus.
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Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. whited@mskcc.org
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