Cytotoxic and targeted systemic therapy in advanced and recurrent cervical cancer: experience from clinical trials

Cervical cancer is the third most common malignant disease of women worldwide. Despite advances in screening and treatment strategies, a significant number of patients have advanced and recurrent disease. These patients are not amenable to curative treatments, such as surgery and radiation, and have poor prognosis. Therefore, palliative treatment remains the standard of care for these patients. Several phase II/III trials have demonstrated that cisplatin is the most active single agent, and the combination of cisplatin and paclitaxel is considered a standard regimen for clinical practice and trials in these patients with improved response rates and progression-free intervals. Although other cisplatin doublet chemotherapy regimens were not superior to cisplatin plus paclitaxel, substituting topotecan or gemcitabine for paclitaxel might be helpful for some patients considering different toxicity profiles. Because the response to palliative chemotherapy is poor, several targeted agents including bevacizumab, erlotinib, pazopanib, lapatinib, sunitinib and cetuximab, each of which inhibits cell proliferation and angiogenesis, were evaluated in these patients. Of them, bevacizumab, targeting vascular endothelial growth factor, showed favorable results. Recent phase III trial showed that bevacizumab combined with chemotherapy was shown to significantly improve the response rate, progression-free interval, and overall survival compared to chemotherapy alone. These results suggest that targeted agents could significantly improve survival and affect practice guidelines in these patients showing poor prognosis. Thus, future trials using newly developed targeted agents are warranted to improve treatment strategies in these patients.