Randomized, open-label phase 2 study comparing frontline dovitinib versus sorafenib in patients with advanced hepatocellular carcinoma.

UNLABELLED: Angiogenesis inhibition by the vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) inhibitor sorafenib provides survival benefit in hepatocellular carcinoma (HCC); however, angiogenic escape from sorafenib may occur due to angiogenesis-associated fibroblast growth factor receptor (FGFR) pathway activation. In addition to VEGFR and PDGFR, dovitinib inhibits FGFR. Frontline oral dovitinib (500 mg/day, 5 days on, 2 days off; n = 82) versus sorafenib (400 mg twice daily; n = 83) was evaluated in an open-label, randomized phase 2 study of Asian-Pacific patients with advanced HCC. The primary and key secondary endpoints were overall survival (OS) and time to tumor progression (TTP) as determined by a local investigator, respectively. Patients included in the study were ineligible for surgical and/or locoregional therapies or had disease progression after receiving these therapies. The median OS (95% confidence interval [CI]) was 8.0 (6.6-9.1) months for dovitinib and 8.4 (5.4-11.3) months for sorafenib. The median TTP (95% CI) per investigator assessment was 4.1 (2.8-4.2) months and 4.1 (2.8-4.3) months for dovitinib and sorafenib, respectively. Common any-cause adverse events included diarrhea (62%), decreased appetite (43%), nausea (41%), vomiting (41%), fatigue (35%), rash (34%), and pyrexia (30%) for dovitinib and palmar-plantar erythrodysesthesia syndrome (66%) and decreased appetite (31%) for sorafenib. Subgroup analysis revealed a significantly higher median OS for patients in the dovitinib arm who had baseline plasma soluble VEGFR1 (sVEGFR1) and hepatocyte growth factor (HGF) below median levels versus at or above the median levels (median OS [95% CI]: sVEGFR1, 11.2 [9.0-13.8] and 5.7 [4.3-7.0] months, respectively [P = .0002]; HGF, 11.2 [8.9-13.8] and 5.9 [5.0-7.6] months, respectively [P = 0.0002]). CONCLUSION: Dovitinib was well tolerated, but activity was not greater than sorafenib as a frontline systemic therapy for HCC. Based on these data, no subsequent phase 3 study has been planned. (Hepatology 2016;64:774-784).

[Effects of electroacupuncture on synovia free radicals in rabbits with knee osteoarthritis].

OBJECTIVE: To observe the effect of electroacupuncture( EA) on synovia superoxide dismutase (SOD) activity, malondialdehyde (MDA) and nitric oxide (NO) contents in rabbits with knee osteoarthritis (KOA). METHODS: A total of 40 New Zealand rabbits were randomly divided into control, model, massage and EA groups, with 10 cases in each. KOA model was established by gypusum fixing method. EA (1.6-2 Hz, 1-2 mA) was applied to left "Yanglingquan" (GB 34), "Xuehai" (SP 10), "Zusanli" (ST 36) and "Liangqiu" (ST 34) for 25 min, once daily for 21 days. For massage group, the affected knee joint was pressed, kneaded, stretched and rotated repeatedly for 15 min every time, followed by forced running about 100 m. The intra-joint synovia was collected (0.4-0.6 ml) for detecting contents of SOD with xanthine oxidase method, MDA with thiobarbituric acid method and NO with nitrate reductase method. RESULTS: Compared with control group, synovia SOD activity in model group decreased considerably (P<0.05), while MDA and NO contents increased significantly (P<0.05). After 3 weeks' treatment, compared with pre-treatment and model group, synovia SOD activity increased markedly (P<0.05), and MDA and NO contents lowered remarkably in both EA and massage groups (P<0.05). No significant differences were found between EA and massage groups in these 3 indexes (P>0.05). CONCLUSION: Both EA and massage can raise synovia SOD activity and lower MDA and NO content, which may contribute to their effect in relieving knee osteoarthritis in the rabbit.

[Effects of electroacupuncture on synovia IL-1beta and TNF-alpha contents in the rabbit with knee osteoarthritis].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on synovia IL-1beta and TNF-alpha contents in rabbits with knee osteoarthritis (KOA). METHODS: A total of 40 New Zealand rabbits were randomly divided into control, model, massage and EA groups. KOA model was established by gypsum fixing method. EA (2 Hz, 1-3 mA) was applied to left "Xiyan" (EX-LE 5), "Yanglingquan" (GB 34), "Xuehai" (SP 10), "Zusanli" (ST 36) and "Liangqiu" (ST 34) for 30 min, once daily and continuously for 21 days. For massage group, the affected knee joint was pressed, kneaded, stretched and rotated repeatedly for 15 min every time, followed by forced running about 100 m. The intra-joint synovia was collected (0.4-0.6 mL) for detecting the contents of IL-1beta and TNF-alpha with radioimmunoassay. RESULTS: No IL-1beta and TNF-alpha were detected in the synovia in control group, while in the other 3 groups, synovia IL-1beta and TNF-alpha levels increased significantly. Before treatment, no significant differences were found among model, EA and massage groups in the levels of IL-1beta and TNF-alpha (P > 0.05), while after the treatment the two indexes both decreased considerably (P < 0.05). Compared with model group, the two indexes were remarkably lower (P < 0.05), but no significant differences were found between EA and massage groups in synovia IL-1beta and TNF-alpha contents (P > 0.05). CONCLUSION: Both EA and massage can effectively suppress the release of synovia IL-1beta and TNF-alpha in KOA of rabbits, which may contribute to the effect of acupuncture in the treatment of osteoarthritis.