Gemcitabine Gemcitabine is associated with response rates of 20% to 50%, with 15% to 30% in patients who are platinum-resistant (302–306). The principal toxicities are myelosuppression and gastrointestinal. The drug is used in doublet combinations with cisplatin or carboplatin with acceptable responses and toxicities, and in the triplet combination with carboplatin and paclitaxel (304).
Oral Etoposide The most common toxicities with oral etoposide are myelosuppression and gastrointestinal: grade 4 neutropenia is observed in about one-fourth of patients, and 10% to 15% have severe nausea and vomiting (307,308). A study of oral etoposide given for a prolonged treatment (50 mg/m2 daily for 21 days every 4 weeks) had a 27% response rate in 41 women with platinum-resistant disease, 3 of whom had durable complete responses (308). In 25 patients with platinum and taxane-resistant disease, 8 objective responses (32%) were reported.
Hormonal Therapy Tamoxifen is associated with CA125 response rates of 15% to 20% in small studies of patients with recurrent ovarian cancer (309–315). Aromatase inhibitors (e.g., letrozole, anastrozole, and exemestane), which have activity in metastatic breast cancer, are being studied in relapsed ovarian cancer (316). One of the principal advantages of this class of agents is its very low toxicity (317).
Targeted Therapies Knowledge of molecular pathways within normal and malignant cells is leading to the development of cancer treatment agents with specific molecular targets. There is great potential in targeting angiogenesis, in particular vascular endothelial growth factor (VEGF), which plays a major role in the biology of epithelial ovarian cancer (318). There are three main approaches to target angiogenesis: the first is to target VEGF itself, the second to target the VEGF receptor, and the third is to inhibit tyrosine kinase activation and downstream signaling with small molecules that work at the intracellular level.