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      OncoTargets and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the pathological basis of cancers, potential targets for therapy and treatment protocols to improve the management of cancer patients. Publishing high-quality, original research on molecular aspects of cancer, including the molecular diagnosis, since 2008. Sign up for email alerts here. 50,877 Monthly downloads/views I 4.345 Impact Factor I 7.0 CiteScore I 0.81 Source Normalized Impact per Paper (SNIP) I 0.811 Scimago Journal & Country Rank (SJR)

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      Efficacy and safety of apatinib treatment for advanced esophageal squamous cell carcinoma

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          Abstract

          Objective

          No standard chemotherapy is available for patients with advanced esophageal squamous cell carcinoma (ESCC) who have failed prior first-line chemotherapy. The aim of this study was to evaluate the efficacy and safety of apatinib, an oral VEGFR-2 inhibitor, as salvage treatment for advanced ESCC.

          Patients and methods

          After apatinib dosing, the efficacy and toxicity were evaluated in 62 patients with pretreated advanced ESCC from 2014 to 2016 at Zhejiang Cancer Hospital. In addition, survival analysis was performed by the Kaplan–Meier method.

          Results

          Among the 62 patients, 15 achieved partial response while 31 had stable disease with a response rate of 24.2% and a disease control rate of 74.2%. Median progression-free survival (PFS) and overall survival were 115 and 209 days, respectively. Grade 3/4 toxicities (59.7%) were acceptable. Patients with grade 3/4 toxicities showed a longer PFS than those without (136 vs 63 days, P=0.044).

          Conclusion

          Apatinib is efficacious as second- or further-line treatment for advanced ESCC.

          Most cited references18

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          Multicenter phase II study of apatinib, a novel VEGFR inhibitor in heavily pretreated patients with metastatic triple-negative breast cancer.

          Xichun Hu, Jian Jian Zhang, Binghe Xu … (2014)
          Apatinib is an oral, highly potent tyrosine-kinase inhibitor targeting VEGFR2. Phase I study showed the recommended dose of 750 mg/day with substantial antitumor activity. This phase II study aims to evaluate the optimum dose level for the efficacy and safety of apatinib monotherapy in heavily pretreated patients with metastatic triple negative breast cancer (mTNBC) in China. Phase IIa was first performed among 25 patients previously treated with anthracycline and/or taxane. All patients received apatinib 750 mg/day p.o. in a 4-week cycle. Subsequently, a phase IIb study of 59 patients was activated, with the endpoint progression-free survival (PFS). The dosage of drug for the Phase IIb was determined according to safety, tolerability and efficacy from the phase IIa study. As a result of toxicity associated with the 750 mg dose in phase IIa, the recommended initial dose of apatinib in the phase IIb was 500 mg/day. In phase IIb, grade 3/4 hematologic toxicities were thrombocytopenia (13.6%), leukopenia (6.8%), neutropenia (3.4%) and anemia (1.7%). The most frequent grade 3/4 nonhematologic toxicities were hand-foot syndrome, proteinuria, hypertension, and increased ALT. In the 56 evaluable patients, overall response rate and clinical benefit rate (CBR) were 10.7 and 25.0%, respectively. Median PFS and overall survival were 3.3 (95% CI 1.7-5.0) and 10.6 (95% CI 5.6-15.7) months, respectively. Our results indicate that apatinib dose of 500 mg rather than 750 mg is the recommended starting dose for the heavily pretreated mTNBC patients with measurable rate of partial response and PFS. © 2014 UICC.
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            Lung cancer incidence and mortality in China, 2011

            Rongshou Zheng, Hongmei Zeng, Tingting Zuo … (2015)
            Abstract Background The National Central Cancer Registry (NCCR) of China is responsible for cancer surveillance. Cancer registration data from registries located in each province are submitted annually to the NCCR for analysis and publication. The lung cancer incidences, and mortalities were estimated in 2011 in China by NCCR. Methods In 2014, 234 population‐based cancer registries' data in 2011 were submitted to the NCCR and 177 cancer registries' data were selected after quality evaluation. The selected data were classified into urban and rural areas; the crude incidence and mortality rates of lung cancer were calculated by age and gender. Age‐standardized rates were calculated by China and World standard population. The 6th National Population Census data of China was used to estimate the 2011 lung cancer burden in China. Results Lung cancer remained the most common cancer and the leading cause of cancer death in China in 2011. Lung cancer incidence and mortality were higher in men and urban areas than those in women and rural areas. The rates were relatively low in patients under 40 years of age, and dramatically increased after age 40, reaching a peak in patients aged 80–84. Conclusion The burden of lung cancer was serious in China in 2011, especially for men in urban areas. Effective methods of intervention, such as air pollution and smoking controls, should be enhanced in the future.
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              Metabolism and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor apatinib in humans.

              Juefang Ding, Xiaoyan Chen, Zhiwei Gao … (2013)
              Apatinib is a new oral antiangiogenic molecule that inhibits vascular endothelial growth factor receptor-2. The present study aimed to determine the metabolism, pharmacokinetics, and excretion of apatinib in humans and to identify the enzymes responsible for its metabolism. The primary routes of apatinib biotransformation included E- and Z-cyclopentyl-3-hydroxylation, N-dealkylation, pyridyl-25-N-oxidation, 16-hydroxylation, dioxygenation, and O-glucuronidation after 3-hydroxylation. Nine major metabolites were confirmed by comparison with reference standards. The total recovery of the administered dose was 76.8% within 96 hours postdose, with 69.8 and 7.02% of the administered dose excreted in feces and urine, respectively. About 59.0% of the administered dose was excreted unchanged via feces. Unchanged apatinib was detected in negligible quantities in urine, indicating that systemically available apatinib was extensively metabolized. The major circulating metabolite was the pharmacologically inactive E-3-hydroxy-apatinib-O-glucuronide (M9-2), the steady-state exposure of which was 125% that of the apatinib. The steady-state exposures of E-3-hydroxy-apatinib (M1-1), Z-3-hydroxy-apatinib (M1-2), and apatinib-25-N-oxide (M1-6) were 56, 22, and 32% of parent drug exposure, respectively. Calculated as pharmacological activity index values, the contribution of M1-1 to the pharmacology of the drug was 5.42 to 19.3% that of the parent drug. The contribution of M1-2 and M1-6 to the pharmacology of the drug was less than 1%. Therefore, apatinib was a major contributor to the overall pharmacological activity in humans. Apatinib was metabolized primarily by CYP3A4/5 and, to a lesser extent, by CYP2D6, CYP2C9, and CYP2E1. UGT2B7 was the main enzyme responsible for M9-2 formation. Both UGT1A4 and UGT2B7 were responsible for Z-3-hydroxy-apatinib-O-glucuronide (M9-1) formation.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Onco Targets Ther
                Journal ID (iso-abbrev): Onco Targets Ther
                Journal ID (publisher-id): OncoTargets and Therapy
                Title: OncoTargets and therapy
                Publisher: Dove Medical Press
                ISSN (Electronic): 1178-6930
                Publication date Collection: 2017
                Publication date (Electronic): 07 August 2017
                Volume: 10
                Pages: 3965-3969
                Affiliations
                [1 ]Department of Thoracic Oncological Surgery
                [2 ]Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China
                Author notes
                Correspondence: Lifen Wang, Department of Medical Oncology, Zhejiang Cancer Hospital, East Banshan Road, Hangzhou 310022, People’s Republic of China, Tel +86 571 8812 2082, Fax +86 571 8812 2088, Email wanglifen1963@ 123456163.com
                Article
                Publisher ID: ott-10-3965
                DOI: 10.2147/OTT.S132756
                PMC ID: 5558584
                PubMed ID: 28860804
                SO-VID: 45b37e99-0a78-4e86-8ecc-ad768140b17f
                Copyright © © 2017 Li and Wang. This work is published and licensed by Dove Medical Press Limited
                License:

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: esophageal squamous cell carcinoma,apatinib,vascular endothelial growth factor,toxicity
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: esophageal squamous cell carcinoma, apatinib, vascular endothelial growth factor, toxicity

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