Cytotoxic and Targeted Systemic Therapy in Advanced and Recurrent Cervical Cancer: Experience from Clinical Trials

Abstract

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.

Klotho expression in cervical cancer: differential expression in adenocarcinoma and squamous cell carcinoma

“…Klotho is a soluble hormone, and administration of klotho to mice inhibited proliferation of pancreatic cancer cells in vivo 13 19 28. Despite recent advances, the prognosis of patients with metastatic cervical cancer is poor 29. Therefore, a novel therapy for patients who cannot benefit from the current treatments is of urgent need.…”

Molecular mechanisms of cisplatin resistance in cervical cancer

“…The overall response rate is 29.1%–67%, and the median overall survival is 12.87 months in patients with recurrent or advanced cervical cancer receiving the combination chemotherapy. 3 , 5 However, resistance to cisplatin, either intrinsic or acquired resistance, may develop, seriously compromising the efficacy of cisplatin. In this article, we summarize recent advances in our understanding of the mechanisms underlying cisplatin resistance (CPR) in cervical cancer and propose strategies to overcome CPR in cervical cancer.…”

Novel 1, 3-N, O-Spiroheterocyclic compounds inhibit heparanase activity and enhance nedaplatin-induced cytotoxicity in cervical cancer cells

“…Clinical trials have been conducted using drugs that target several different biological agents, including vascular endothelial growth factor and its receptors, histone deacetylase, matrix metalloproteinase, cell cycle checkpoint molecules, notch, and mammal target of rapamycin [3, 4]. The GOG240 clinical study was the first to show that targeted drugs can be effective for treating patients with advanced, recurrent, and persistent cervical cancer [5].…”