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Treatment-related fatigue with everolimus and temsirolimus in patients with cancer—a meta-analysis of clinical trials

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Tumor Biology

Abstract

Mammalian target of rapamycin (mTOR) inhibitors, everolimus and temsirolimus, are approved for the treatment of a variety of malignancies. Fatigue has been described with these agents as a common side effect, although the overall incidence and risk remain unclear. We performed a meta-analysis to calculate the overall incidence of fatigue in cancer patients treated with everolimus and temsirolimus and to compare the differences in incidence with placebo. The electronic databases PubMed, Embase, Web of Science, and Cochrane databases were searched for studies to include in the meta-analysis. Eligible studies were phase II and III prospective clinical trials of cancer patients treated with single drug everolimus or temsirolimus with toxicity data on fatigue. Overall incidence rates, relative risk (RR), and 95 % confidence intervals (CI) were calculated employing fixed or random effects models depending on the heterogeneity of the included studies. A total of 9,760 patients with a variety of malignancies from 56 prospective clinical trials were included for the meta-analysis. The overall incidences of all-grade and high-grade fatigue in cancer patients treated with mTOR inhibitor (everolimus or temsirolimus) were 45.4 % (95 % CI 36.9–55.8 %) and 8.7 % (95 % CI 7.2–10.4 %), respectively. The relative risks of fatigue of mTOR inhibitor compared to placebo were increased for all-grade (RR = 1.22, 95 % CI 1.08–1.38, P = 0.002) and high-grade (RR = 1.82, 95 % CI 1.24–2.69, P = 0.002) fatigue. The incidence of all-grade fatigue of patients treated with everolimus was higher than those with temsirolimus (RR = 1.85, 95 % CI 1.71–2.01, P < 0.001). No significant difference was detected with between everolimus and temsirolimus in terms of high-grade fatigue (RR = 1.15, 95 % CI 0.94–1.41, P = 0.18). Treatment with mTOR inhibitor, everolimus and temsirolimus, is associated with an increased incidence of fatigue in patients with cancer. Early detection and management of fatigue is needed.

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Acknowledgments

We are indebted to the authors of the primary studies.

This study was supported by a grant from the Natural Science Foundation of Zhejiang Province, China (Grant number: LQ13H160010) and a grant from Doctoral Fund of Ministry of Education of China (Grant Number: 20130101120091).

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Authors and Affiliations

  1. Department of Thoracic Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China

    Ling Peng & Qiong Zhao

  2. Zhejiang Food and Drug Administration, Hangzhou, Zhejiang Province, China

    Yun Zhou

  3. Department of Radiation, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China

    Xianghua Ye

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Peng, L., Zhou, Y., Ye, X. et al. Treatment-related fatigue with everolimus and temsirolimus in patients with cancer—a meta-analysis of clinical trials. Tumor Biol. 36, 643–654 (2015). https://doi.org/10.1007/s13277-014-2669-3

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