Clinical response and safety of apatinib monotherapy in recurrent, metastatic cervical cancer after failure of chemotherapy: a retrospective study / 부인종양

Effects of Wuzhi Capsules on in vivo Pharmacokinetic Behavior of Apatinib Mesylate in Rats / 中国药房

OBJECTIVE： To establish a method for the concentration determination of apatinib mesylate in plasma of rats， and to investigate the effects of single and multiple administration of Wuzhi capsules on the pharmacokinetic behavior of apatinib mesylate in rats. METHODS：  LC-MS/MS method was used to detect the plasma concentration of apatinib mesylate in rats. Using carbamazepine as internal standard， the determination was performed on Waters XBridge BEH C18 column with mobile phase consisted acetonitrile-0.1％ formic acid solution （45 ∶ 55，V/V） at the flow rate of 0.3 mL/min. The column temperature was 40 ℃. The temperature of injector was 15 ℃， and the sample size was 2 μL. ESI was used for positive ion scanning in MRM mode. The ion pairs m/z used for quantitative analysis were 398.1→212.1 （apatinib mesylate） and  237.2→194.2 （internal standard）. The rats were randomly divided into control group Ⅰ， observation group Ⅰ， control group Ⅱ， observation group Ⅱ， with 6 rats in each group. Control group Ⅰ were given single administration of apatinib mesylate intragastrically （50 mg/kg， similarly hereinafter）. Observation group Ⅰ was given Wuzhi capsules intragastrically （450 mg/kg， similarly hereinafter）， and then 10 min later given apatinib mesylate intragastrically. Control group Ⅱ was given normal saline intragastrically， once a day， for consecutive 7 d， and then were given single administration of apatinib mesylate. Observation group Ⅱ was given Wuzhi capsules intragastrically， once a day， for consecutive 7 d， and then 10 min later were given single administration of apatinib mesylate. The blood samples were collected from intraocular canthus vein plexus and determined 0.25， 0.5， 1.0， 2.0， 2.5， 3.0， 4.0， 6.0， 8.0， 12.0， 24.0 h after intragastric administration， respectively. Pharmacokinetic parameters were apatinib mesylate were calculated and compared among those groups by using DAS 2.1 software and t-test. RESULTS： The linear range of apatinib mesylate were 2-2 000 ng/mL. The lower limit of quantitation was 2 ng/mL. RSDs of intra- day and inter-day were all lower than 10％， and the accuracy were 94.93％-104.68％. Matrix effect did not affect the quantitative analysis of the substance to be measured. Compared with control group Ⅰ， cmax， AUC0-24 h and AUC0-∞ of observation group Ⅰ were increased significantly， CLZ was decreased significantly （P＜0.05）. Compared with control group Ⅱ， AUC0-24 h and AUC0-∞ of observation group Ⅱ were increased significantly， and CLZ was decreased significantly （P＜0.05）. Compared with observation group Ⅰ， AUC0-24 h and AUC0-∞ of observation group Ⅱ were decreased significantly （P＜0.05）. CONCLUSIONS： Established LC-MS/MS method is sensitive and specific， and can be used for the concentration determination of apatinib mesylate in plasma of rats. Wuzhi capsules can influence in vivo pharmacokinetic behavior of apatinib mesylate in rats. The effect of multiple administration of Wuzhi capsules is weaker than that of single administration.

Efficacy and safety of TACE combined with apatinib mesylate tablets in the treatment of intermediate and advanced hepatoma / 肿瘤

Objective: To explore the difference of curative effect between transcather arterial chemoembolization (TACE) combined with apatinib mesylate tablets and TACE alone in the treatment of intermediate and advanced primary hepatoma. Methods: Total of 60 patients with intermediate and advanced hepatoma treated by TACE were divided into the observation group (30 cases) and the control group (30 cases) according to whether TACE combined with apatinib mesylate tablets or not. The serum levels of alpha-fetoprotein (AFP), vascular endothelial growth factor (VEGF), and matrix metalloproteinase-9 (MMP-9) before and 3 months after the treatment were compared. And the objective remission rate, overall survival, and the incidence of adverse effects between the two groups were also compared. Results: The serum levels of AFP, VEGF, and MMP-9 before treatment were not significantly different between the two groups (all P > 0.05), but the ones were all decreased in the two groups 3 months after treatment (all P 0.05). However, the occurrence rates of hypertension, proteinuria, hand-foot syndrome, and rash in the observation group were significantly higher than those in the control group (all P < 0.05). Conclusion: Compared with the treatment of TACE alone, TACE combined with apatinib mesylate can get better clinical efficacy and survival in the treatment of intermediate and advanced primary hepatoma, but with an increased adverse effects rate.

Clinical research on apatinib mesylate combined with multiple antigens specific cell therapy in treatment of osteosarcoma and soft tissue sarcoma (small sample report) / 中国免疫学杂志

Objective: To evaluate the effect and safety of molecular targeted therapy of apatinib mesylate combined with multiple antigen stimulatiing cellular therapy in treatment of osteosarcoma and soft tissue sarcoma. Methods:Six patients with sarcoma were collected by the failure of surgery, radiation and chemotherapy treatment or refusal surgery, radiation and chemotherapy, and at least one month from the last treatment of surgery, radiation and chemotherapy. All of the patients at least received three cycle MASCTTM . From Day 1,everyone were given Apatinib 500 mg,po,qd ,until the disease progression. To measure the patient’s quality of life depending on EORTC QLQ-C30,meanwhile,detecting the cellular immunity function and circulating tumor cells(CTCs) of patients before treatment and one month after 3 cycle MASCTTM . At last, monitoring the cellular immune responses by the Enzyme-linked immuno spot ( ELISPOT) assay. Results: All of the four patients completed the treatment of 3 cycle MASCTTM . Only one patient reduced apatinib from 500 mg to 250 mg because of palmar-plantar erythrodyses-thesia. The response rates of the four patients received MASCTTM and apatinib mesylate after treatment were 1 for complete response (CR),3 for partial response (PR). The life quality and cellular immunity function were improved in all of the patients. ELISPOT assay suggested that the majority of antigen peptides could induce specific cytotoxic T lymphocytes( CTLs) response. The Progression-Free-Survival ( PFS) of four patients received MASCTTM and apatinib mesylate was 7,6,9 and 4 months ,while the response rates of the two patients received apatinib mesylate were 1 for ( Stable disease) SD,one for ( Progression disease) PD. And PFS of the two patients were one month and two months. Conclusion:Combination of MASCTTM and apatinib mesylate is safe,effective and were good prospects for application.

Research of rational use of apatinib mesylate / 中国药学杂志

OBJECTIVE: To investigate and analyze the rational use of apatinib in cancer hospital. METHODS: Retrospective study was applied. Through reviewing medical records, the patient' s basic information, drug therapy information and adverse drug effects were collected and analyzed. RESULTS: Apatinib is mainly used in patients with advanced metastatic gastric or esophagogastric junction cancer who have failed at least two chemotherapeutic regimens. The clinical common dose of apatinib was 0.25 or 0.5 g, less than the dose of 0.85 g recommended in drug instruction. CONCLUSION: Apatinib is a new choice for gastric or esophagogastric junction cancer. It has demonstrated tolerable adverse effects in these patients. However, at present, more attentions should be paid to possible effect of drug dose on clinical outcome.