Sunitinib® in Patients With Recurrent Ovarian Clear Cell Carcinoma

Ovarian cancer is the 10th leading cancer in women in Taiwan. There were 894 new cases in 2004 and 297 women died of ovarian cancer in 2001 according to the data released by the Department of Health. The incidence of epithelial ovarian cancer increases with age and the median age at the time of diagnosis is 63 years, and 70% of patients present with advanced disease. Primary treatment for ovarian cancer consists of appropriate surgical staging and cytoreductive surgery, followed in most patients by systemic chemotherapy. Initial surgery should be a comprehensive staging laparotomy. For patients with clinical stage III or IV disease, the usual recommendation continues to be maximally cytoreductive surgery followed by adjuvant chemotherapy. Most patients with epithelial ovarian cancer will receive postoperative systemic chemotherapy. Observation is recommended for stage Ia, grade 1 tumors, owing to their high cure rate. For patients with higher-grade and/or higher-stage tumors, systemic chemotherapy is indicated. The recommendation for specific primary chemotherapy/primary adjuvant therapy is Paclitaxel plus platinum regimens. Paclitaxel plus cisplatin or carboplatin are the recommended regimens. The extent of treatment varies with stage of disease. For patients with advanced-stage disease, six cycles of chemotherapy are recommended, whereas for earlier-stage disease, three to six cycles are recommended, pending the results of ongoing studies in this group of patients. Treatment of relapsed ovarian cancer Despite the high objective response rate associated with primary platinum/taxane-based chemotherapy in advanced ovarian cancer, the majority of patients will eventually experience disease recurrence and be potential candidates for a second-line treatment approach. Treatment options for relapsed cancer are numerous. Patients with platinum-sensitive tumors (response to initial platinum therapy with no relapse for at least 6 months) may be retreated with platinum agents and/or taxanes upon relapse. Clear cell carcinomas of the ovary comprise approximately 5% of all ovarian neoplasms and exhibit unique features including a more aggressive clinical course and more malignant behavior. Clinically, clear cell carcinomas often present as a large pelvic mass, the majority of which are detected at an early stage (FIGO stage I). Despite the early stage diagnosis, survival rates are significantly lower for women with clear cell carcinoma relative to stage-matched serous adenocarcinoma of the ovary. Furthermore, tumors are more chemoresistant, resulting in a high degree of recurrence and exhibit more frequent early metastasis to lymph nodes and parenchymal organs. Sunitinib is a small molecule with anti-tumor properties pharmacologically mediated through inhibition of multiple receptor tyrosine kinase (RTKs), which are important regulators of tumor cell growth, angiogenesis, and metastasis. Specifically, sunitinib is a potent ATP-competitive inhibitor of the catalytic activity of a group of closely related RTKs consisting of VEGFR-1, -2, and -3, PDGFR-α and -β, KIT, CSF-1R, FLT-3, and RET. Due to its multi-targeted profile, the pharmacological activity of sunitinib is likely mediated by inhibition of multiple RTK targets and multiple pathways. In this study, we would like to evaluated the effect of Sunitinib in recurrent / persisted ovarian clear cell carcinoma.