title: Muscle wasting associated with the long-term use of mTOR inhibitors.
abstract: Some targeted therapies alter muscle mass due to interference with pathways of muscle metabolism. The effects of mammalian target of ra pamycin (mTOR) inhibitors on muscle mass have yet to be fully elucidated. In the present study, the computerized tomography (CT) scans of patients receiving mTOR inhibitors for at least 6 months taken at baseline and post-therapy were retrospectively retrieved, and body composition analyses were performed using the software, sliceOmatic version 5.0 (TomoVision, Inc., Magog, QC, Canada). The difference in body composition parameters was evaluated for significance. The time to treatment (TTF) failure was also compared between the sarcopenic and non-sarcopenic patients at the baseline. Of the 75 patients studied, 20 matched the inclusion criteria (including 16 males). The mean duration between the CT scans was 14.4±2.0 months. A total of 12 (60%) patients were sarcopenic at the baseline, whereas three more (75% in total) became sarcopenic following treatment. The use of mTOR inhibitors significantly decreased the skeletal muscle area (P=0.011) and lean body mass (P=0.007), although it had no effect on adipose tissue (P=0.163) or body weight (P=0.262). The rate of skeletal muscle wasting was 2.6 cm2/m2, or 2.3 kg in 6 months. The TTF did not differ between sarcopenic and non-sarcopenic patients, and was not significantly associated with any other parameter. To the best of our knowledge, this is the first study to demonstrate that the long-term use of mTOR inhibitors induces a marked loss of muscle mass. Due to the predictive and prognostic role of sarcopenia in cancer patients, these findings may have important clinical implications.
authors.affiliation: Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Aichi 466-8560, Japan.
authors.forename: Bishal
authors.initials: B
authors.lastname: Gyawali
authors.affiliation: Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Aichi 466-8560, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Shimokata
authors.affiliation: Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Aichi 466-8560, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Honda
authors.affiliation: Department of Medical Oncology, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Aichi 453-8511, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Kondoh
authors.affiliation: Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Aichi 466-8560, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Hayashi
authors.affiliation: Department of Urology, Nagoya University Graduate School of Medicine, Nagoya University Hospital, Nagoya, Aichi 466-8560, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yoshino
authors.affiliation: Department of Urology, Nagoya University Graduate School of Medicine, Nagoya University Hospital, Nagoya, Aichi 466-8560, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Sassa
authors.affiliation: Department of Medical Oncology, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Aichi 453-8511, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Nakano
authors.affiliation: Department of Urology, Nagoya University Graduate School of Medicine, Nagoya University Hospital, Nagoya, Aichi 466-8560, Japan.
authors.forename: Momokazu
authors.initials: M
authors.lastname: Gotoh
authors.affiliation: Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Aichi 466-8560, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ando
keywords: cancer cachexia; mTOR inhibitors; mammalian target of rapamycin; sarcopenia; skeletal muscle index; skeletal muscle mass