BACKGROUND: mTOR inhibitors are currently used in the treatment of solid malignancies. Since their approval, several cases of pulmonary toxicity (PT) have been described. This analysis aims to report the incidence and the risk of PT in published randomized controlled trials. MATERIAL AND METHODS: PubMed and Scopus were reviewed for phase II-III randomized controlled trials with temsirolimus and everolimus. The characteristic of each study and incidence of all- and high-grades PT were collected. RESULTS: A total of 2233 patients were available for meta-analysis: 989 had breast cancer, 833 had neuroendocrine tumor and 411 had metastatic renal cell carcinoma. In patients taking mTOR inhibitors, the incidence of all- and high-grades PT was 10.4% and 2.4%, respectively. Compared to controls, the relative risk for all- and high-grades PT was 31- and 8.8-folds, respectively. No significant heterogeneity was observed between the studies. Not any relationship was found between the incidence of lung metastases, treatment exposure and the incidence of PT. CONCLUSIONS: The high grade PT is a rare event and 10% of patients may experience mild grade toxicity with a worsening of quality of life and interruption of therapy in some cases. We recommend monitoring of PT in patients treated with mTOR inhibitors.
BACKGROUND:mTOR inhibitors are currently used in the treatment of solid malignancies. Since their approval, several cases of pulmonary toxicity (PT) have been described. This analysis aims to report the incidence and the risk of PT in published randomized controlled trials. MATERIAL AND METHODS: PubMed and Scopus were reviewed for phase II-III randomized controlled trials with temsirolimus and everolimus. The characteristic of each study and incidence of all- and high-grades PT were collected. RESULTS: A total of 2233 patients were available for meta-analysis: 989 had breast cancer, 833 had neuroendocrine tumor and 411 had metastatic renal cell carcinoma. In patients taking mTOR inhibitors, the incidence of all- and high-grades PT was 10.4% and 2.4%, respectively. Compared to controls, the relative risk for all- and high-grades PT was 31- and 8.8-folds, respectively. No significant heterogeneity was observed between the studies. Not any relationship was found between the incidence of lung metastases, treatment exposure and the incidence of PT. CONCLUSIONS: The high grade PT is a rare event and 10% of patients may experience mild grade toxicity with a worsening of quality of life and interruption of therapy in some cases. We recommend monitoring of PT in patients treated with mTOR inhibitors.
Authors: Li Li; Henry Mok; Pavan Jhaveri; Mark D Bonnen; Andrew G Sikora; N Tony Eissa; Ritsuko U Komaki; Yohannes T Ghebre Journal: Expert Rev Anticancer Ther Date: 2018-07-23 Impact factor: 4.512
Authors: Kelvin Teck-Hong Kuik; Jason Trubiano; Leon J Worth; Nur-Shirin Harun; Daniel Steinfort; Douglas Johnson Journal: Med Mycol Case Rep Date: 2014-09-16
Authors: Michael O Palumbo; Petr Kavan; Wilson H Miller; Lawrence Panasci; Sarit Assouline; Nathalie Johnson; Victor Cohen; Francois Patenaude; Michael Pollak; R Thomas Jagoe; Gerald Batist Journal: Front Pharmacol Date: 2013-05-07 Impact factor: 5.810