Chinese multidisciplinary expert consensus on the management of adverse drug reactions associated with savolitinib / 中华肿瘤杂志

MET gene is a proto-oncogene, which encodes MET protein with tyrosine kinase activity. After binding to its ligand, hepatocyte growth factor, MET protein can induce MET dimerization and activate downstream signaling pathways, which plays a crucial role in tumor formation and metastasis. Savolitinib, as a specific tyrosine kinase inhibitor (TKI) targeting MET, selectively inhibits the phosphorylation of MET kinase with a significant inhibitory effect on tumors with MET abnormalities. Based on its significant efficacy shown in the registration studies, savolitinib was approved for marketing in China on June 22, 2021 for the treatment of advanced non-small cell lung cancer with MET 14 exon skipping mutations. In addition, many studies have shown that MET TKIs are equally effective in patients with advanced solid tumors with MET gene amplification or MET protein overexpression, and relevant registration clinical studies are ongoing. The most common adverse reactions during treatment with savolitinib include nausea, vomiting, peripheral edema, pyrexia, and hepatotoxicity. Based on two rounds of extensive nationwide investigations to guide clinicians, the consensus is compiled to use savolitinib rationally, prevent and treat various adverse reactions scientifically, and improve the clinical benefits and quality of life of patients. This consensus was prepared under the guidance of multidisciplinary experts, especially including the whole-process participation and valuable suggestions of experts in Traditional Chinese Medicine, thus reflecting the clinical treatment concept of integrated Chinese and western medicines.

[Effects of Dioscorea septemloba on the biomechanical and bone histomorphometric parameters of femur in the ovariectomized rats].

OBJECTIVE: To investigate the effects of the decoction of Rhizoma Dioscoreae septemlobae (RD) on the biomechanical and bone histomorphometric parameters of femur in the ovariectomized rats. METHODS: 25 female Wistar rats without pregnancy and deliver were divided into 5 groups randomly: sham (sham-operation), ovariectomy (OVX), OVX + high dosage RD (4 g/kg x d), OVX + middle dosage RD (2 g/kg x d) and OVX + low dosage RD (1 g/kg x d), n = 5 in every group. After intragastric administration 12-week period continuously, the biomechanical and the bone histomorphometric parameters of the femur of the rats in every group were determined, respectively, including percentage of trabecular bone volume (TBV%), percentage of trabecular osteoid (TOS%), mean osteoid width (MOSW), percentage of mineralizing surface (MdS%), percentage of double mineralizing surface (DMds%), percentage of DMds/MdS (%), percentage of travecular formation surface (TFS%), percentage of trabecular resorption surface (TRS%), mineral apposition rate (MAR), mineralizing lag time (MLT). RESULTS: The maximum loading, deflection, the maximum strain of the femur in the OVX group was 125.78 +/- 15.48 (N), 1.87 +/- 0.22 (mm), 9.34 +/- 1.10 (%), it was significantly lower than that in the sham group ( P< 0.05, P < 0.01), respectively. The maximum loading and maximum stress was increased in different extent in the every dose group of OVX + RD, respectively. TBV% of femur was significantily lower in the OVX group than that in the sham group (P < 0.01). The MdS%, DMds%, DMds/MdS (%), TOS%, MOSW, TRS%, MAR was significantly higher in the OVX group than that in the sham group, respectively (P < 0.01). In the RA high and middle dosage group, the TBV% of femur was significantly higher than that in the model group (P < 0.05), and the MdS%, DMds%, DMds/MdS (%), TRS%, TOS%, MOSW, MAR was significantly lower than that in the model group, respectively (P < 0.05), and MLT was decurtated slightly (P > 0.05). CONCLUSION: The decoction of RD can decline the bone turnover and the loss of bone of femur in the ovariectomized rats.

[Effects of Dioscorea septemloba on bone metabolism in ovariectomized rats].

OBJECTIVE: To investigate the effects of the decoction of Rhizoma Dioscorea septemlobae (RD) on the bone metabolism in ovariectomized rats. METHOD: Thirty female, 3-month-old Wistar rats without pregnancy and deliver were randomly divided into 6 groups: sham (sham-operation), ovariectomy (OVX), OVX + diethylstilbestrol, OVX + high dose RD (4 g x kg(-1) x d(-1)), OVX + middle dose RD (2 g x kg(-1) x d(-1)) and OVX + low dose RD (1 g x kg(-1) x d(-1)) (n = 5 in every group). After 12-week period of continuous treatment, the urinary samples and blood samples were collected for the determination of serum estrodiol (E2), calcium (Ca), phosphorus (P), bone glaprotein (BGP), alkaline phosphatase (ALP), urinary calcium/creatinine (Ca/Cr), phosphorus/ creatinine (P/Cr) and deoxypyridioline/creatinine (DPD/Cr). The uteri were removed and weighed. The bone mineral density (BMD) and the biomechanical parameters of the femur of the rats in every group were determined, respectively. RESULT: The coefficient of uteri in every dose group of OVX + RD was significantly higher than that in the OVX group (P < 0.01). The concentration of serum ALP, BGP and urinary DPD/Cr, Ca/Cr in the OVX group was significantly higher than that in the sham group (P < 0.05), respectively, However, that in the every dose of OVX + RD was lower than that in the OVX group, respectively. There was no significan difference in the concentration of serum Ca, P and urinary P/Cr in every group, respectively. The bone mineral density (BMD) in the OVX group was (0.032 +/- 0.007) g x cm(-2) and was significantly lower than that in the sham group (P < 0.01). However, the value in the group of every dose OVX + RD was significantly higher than that in the OVX group (P < 0.05, P < 0.01), respectively. The maximum loading, deflection and the maximum strain of the femur in the OVX group were (125.78 +/- 15.48) N, (1.87 +/- 0.22) mm, (9.34 +/- 1.10) % and were significantly lower than those in the sham group (P < 0.05, P < 0.01), respectively. The maximum loading and maximum stress were increased in different extent in the every dose group of OVX + RD, respectively. CONCLUSION: The decoction of RD can inhibit bone absorption, decline bone turnover and improve the loss of bone in ovariectomized rats.

Effects of Dioscorea septemloba on bone metabolism in ovariectomized rats / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effects of the decoction of Rhizoma Dioscorea septemlobae (RD) on the bone metabolism in ovariectomized rats.</p><p><b>METHOD</b>Thirty female, 3-month-old Wistar rats without pregnancy and deliver were randomly divided into 6 groups: sham (sham-operation), ovariectomy (OVX), OVX + diethylstilbestrol, OVX + high dose RD (4 g x kg(-1) x d(-1)), OVX + middle dose RD (2 g x kg(-1) x d(-1)) and OVX + low dose RD (1 g x kg(-1) x d(-1)) (n = 5 in every group). After 12-week period of continuous treatment, the urinary samples and blood samples were collected for the determination of serum estrodiol (E2), calcium (Ca), phosphorus (P), bone glaprotein (BGP), alkaline phosphatase (ALP), urinary calcium/creatinine (Ca/Cr), phosphorus/ creatinine (P/Cr) and deoxypyridioline/creatinine (DPD/Cr). The uteri were removed and weighed. The bone mineral density (BMD) and the biomechanical parameters of the femur of the rats in every group were determined, respectively.</p><p><b>RESULT</b>The coefficient of uteri in every dose group of OVX + RD was significantly higher than that in the OVX group (P < 0.01). The concentration of serum ALP, BGP and urinary DPD/Cr, Ca/Cr in the OVX group was significantly higher than that in the sham group (P < 0.05), respectively, However, that in the every dose of OVX + RD was lower than that in the OVX group, respectively. There was no significan difference in the concentration of serum Ca, P and urinary P/Cr in every group, respectively. The bone mineral density (BMD) in the OVX group was (0.032 +/- 0.007) g x cm(-2) and was significantly lower than that in the sham group (P < 0.01). However, the value in the group of every dose OVX + RD was significantly higher than that in the OVX group (P < 0.05, P < 0.01), respectively. The maximum loading, deflection and the maximum strain of the femur in the OVX group were (125.78 +/- 15.48) N, (1.87 +/- 0.22) mm, (9.34 +/- 1.10) % and were significantly lower than those in the sham group (P < 0.05, P < 0.01), respectively. The maximum loading and maximum stress were increased in different extent in the every dose group of OVX + RD, respectively.</p><p><b>CONCLUSION</b>The decoction of RD can inhibit bone absorption, decline bone turnover and improve the loss of bone in ovariectomized rats.</p>