Advances In The Treatment Of Epithelial Ovarian Cancer

Epithelial ovarian cancer is a significant cause of morbidity and the commonest cause of death fromgynecologic cancer. For most patients presenting with stage III-IV disease, first-line treatmentconsists of debulking surgery and chemotherapy with a platinum- taxane doublet, most commonlycarboplatin and paclitaxel. Despite frequent complete responses to first-line treatment, relapseoccurs in up to 85% of patients with stage III-IV disease, with a median time to relapse of 18 months.Approximately a third of these relapses occur within 6 months of first-line treatment, and thedisease is then considered primary platinum resistant or refractory. Single-agent treatment with anonplatinum drug is the preferred treatment option in this setting; commonly used drugs arepegylated liposomal doxorubicin (PLD), topotecan, and, more recently, weekly paclitaxel. However,outcomes are poor, with response rates ranging from 6% to 12% for PLD and topotecan, and 27% to35% for weekly paclitaxel. Median progression-free survival (PFS) and overall survival (OS)typically range from 3 to 6 months and from 10 to 13 months, respectively, with some improvementin the latter in more recent studies, particularly those incorporating weekly paclitaxel. However,platinum resistance is generally not absolute. Response rates of 29% to 39% have been reported insmall studies of platinum-based regimens such as cisplatin- etoposide, cisplatin- gemcitabine, oroxaliplatin- 5-fluorouracil in platinum-resistant patients, suggesting that combination cisplatin oroxaliplatin containing chemotherapy can overcome platinum resistance in some patients.Consequently, efforts are being made to try new platinum-based combinations both in the platinumsensitive and the platinum-resistant setting. Few studies demonstrated a response rate of 41%for recurrent ovarian cancer, relapsing within 12 months of prior platinum treatment, using the 3-drug combination of epirubicin, cisplatin, and continuous infusional 5-fluoruracil. Because thedelivery of infusional 5-fluorouracil requires an indwelling central venous catheter, the samegroup investigated the combination of epirubicin, carboplatin, and the oral fluoropyrimidinecapecitabine (ECarboX) in patients with disease relapsing 6 months or more after prior platinumtreatment. Eleven (61%) of 18 patients demonstrated either complete or partial radiologicresponse, implying considerable activity of this combination. However, hematologic toxicity wassignificant, necessitating frequent dose reductions and interruptions. These encouraging reportsof preliminary activity have led to the frequent use of a modified ECarboX regimen in someinstitutions for fit patients with platinum-refractory or resistant relapse. Specifically, weresubstituted cisplatin for carboplatin to ameliorate haematologic toxicity, leading to a regimen ofepirubicin, cisplatin, and capecitabine(ECX).