Evaluation of the Efficacy of 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
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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
The tumor response will be assessed according to World Health Organization (WHO) response criteria or Rustin's criteria: Complete response (CR) Complete disappearance of all clinically detectable lesions for a minimum of 4 weeks. Clinical condition and performance status remains stable or improve. Partial response (PR) 50% or more decrease in the sum of the products of perpendicular diameters of all measurable lesions or tumor marker-CA125 for a minimum of 4 weeks. Clinical condition and performance status remains stable or improve. Stable disease (SD) A decrease of less than 50% or an increase of less than 25% of the sum of the products of perpendicular diameters of all measurable lesions or tumor marker CA125 with no development of new lesions for at least 4 weeks. Progressive disease (PD) Occurrence of new lesions; an increase of 25% or more in the sum of the areas of original measurement, or an elevated 25% of tumor marker CA125.
4 weeks after completion of treatment
Chih-Ming Ho, Ph.D.
Cathay General Hospital
Taiwan: Department of Health