Clinical Study of Apatinib in the Treatment of Platinum Resistant Recurrent Ovarian Cancer

The overall 5-year survival rate of ovarian cancer is 45%. The mortality rate of ovarian cancer accounts for the first in gynecologic cancer deaths. Ovarian cytoreductive surgery and postoperative platinum based chemotherapy are the standard treatment for advanced ovarian cancer. About 80% of ovarian cancer will eventually show relapse and metastasis. All patients with recurrent ovarian cancer will eventually develop into "platinum resistance". Platinum resistance was found in 1-6 months with platinum-free interval. There is no standard treatment protocol for recurrent ovarian cancer of "platinum resistant," usually with platinum-free single chemotherapy, such as: paclitaxel, docetaxel, liposomal doxorubicin, gemcitabine, topotecan and other. The response rate was 10%-30%, the median progression free survival was \<4 months, and the median overall survival time was 12 months with platinum-free single-agent chemotherapy. The incidence of grade 3-4 hematologic or non-hematologic toxicity is about 40%. And chemotherapy has 14% mortality rate within 30 days of the start of single-agent chemotherapy in the literature reported. VEGF plays an important role in invasion and metastasis of ovarian cancer. VEGF directly stimulates tumor cell proliferation, growth and migration, and promotes ovarian cancer metastasis. The growth and metastasis of ovarian cancer cells are related to the quantity of VEGF. It has confirmed that inhibition of VEGF function can inhibit angiogenesis and inhibit the growth and metastasis of ovarian cancer cells in vivo experiments. The Chinese State Food and Drug Administration approved small molecular targeting drug, apatinib, for the treatment of advanced gastric cancer, for approval in December 13, 2014. The role of apatinib is the intracellular ATP binding site of VEGFR2 tyrosine receptor, which blocks the signal transduction of VEGF binding and leads to tumor angiogenesis inhibition. Apatinib can inhibit VEGFR2 effectively at a very low concentration, and a higher concentration can inhibit the platelet derived growth factor receptor (PDGFR), c-Kit and c-Src. Apatinib has only 20% grade 3-4 hematological and non hematological toxicity in the treatment of metastatic gastric cancer and gastro-esophageal junction adenocarcinoma. Deng et al reported one cases of progressive ovarian cancer. After 4-line chemotherapy resistance, a daily oral apatinib 500 mg was taken and a longer progression free survival (11.3 months) was obtained. Xie Congying et al of the First Affiliated Hospital of Wenzhou Medical University had a report in the 2017 ESMO conference. The report reviewed 15 cases of recurrent and metastatic ovarian cancer with a single drug atapatinib in the treatment of more than 2 lines of chemotherapeutic drug resistance. The median progression free survival was 5 months, the objective remission rate was 53.3% and the disease control rate was 73.3%. It is known from the above reports that apatinib has good efficacy and low toxicity in the treatment of "platinum resistant" recurrent ovarian cancer, but there is lack of prospective study.