Topotecan in cervical cancer

Recurrent and advanced cervical cancers are associated with high mortality and a lack of effective treatment options, especially for women who are poor candidates for surgery or radiation therapy. The broad clinical effectiveness and manageable toxicity of topotecan in other human malignancies as well as promising recent study results suggest that it is highly effective in treating cervical tumors. We therefore conducted a systematic review on the studies using topotecan in cervical cancer. Seven phase I-III clinical trials using topotecan, both as a single agent and in combination with cisplatin or paclitaxel, in patients with recurrent or advanced carcinoma of the cervix were reviewed. Data from two studies in which topotecan was used in combination with radiotherapy for induction therapy were also evaluated. Although single-agent cisplatin-based chemoradiotherapy is the standard of care for high-risk or locally advanced cervical cancer, topotecan, when used concurrently with cisplatin and/or radiation therapy, produces high objective response rates and prolonged survival. Gynecologic Oncology Group (GOG) Protocol 179 for the first time showed significantly improved overall survival and progression-free survival in a combination therapy for advanced cervical cancer compared to cisplatin alone. Recent data suggest that topotecan, when used concurrently with cisplatin, may be the new standard of care for the management of recurrent or advanced cervical cancer. Ongoing phase III studies (GOG-204, AGO-Zervix-1) will compare this combination with other cisplatin-containing and cisplatin-free combinations. Moreover, further evaluation of topotecan appears to be warranted in conjunction with radiotherapy and in the neoadjuvant setting as well as in combination with novel biologic agents.