A Critical Analysis of the Impact of Etoposide as a Topoisomerase II Inhibitor in Cervical Cancer Treatment: A Review.

[BACKGROUND] Etoposide is a semisynthetic derivative of podophyllotoxin and an FDA-approved topoisomerase II inhibitor that induces DNA strand breaks leading to cancer cell death. Cervical cancer remains the fourth most common cancer among women worldwide, with platinum-based chemotherapy constituting the standard of care. Although etoposide has demonstrated broad anticancer activity, its role in cervical cancer therapy is considered secondary and is mainly explored in combination regimens.

[METHODS] This review summarizes published clinical and preclinical studies evaluating the use of etoposide in cervical cancer, both as monotherapy and in combination with other chemotherapeutic agents. Emphasis is placed on treatment regimens, disease stages, routes of administration, limitations, and emerging strategies aimed at improving therapeutic outcomes.

[RESULTS] The etoposide has been administered orally or intravenously and has shown clinical benefit primarily when used in combination therapies, including cisplatin, topotecan, mitomycin, epirubicin, doxorubicin, vincristine, cyclophosphamide, bevacizumab, and adriamycin. Its application is mainly observed in FIGO stage IA2-IB2, as well as in recurrent or metastatic cervical cancer. However, platinum-based regimens, particularly cisplatin or carboplatin combined with paclitaxel, topotecan, fluorouracil, or bevacizumab, remain superior in efficacy. Limitations such as drug resistance and systemic toxicity have restricted the widespread use of etoposide. Recent research has focused on nanocarriers, dual inhibitors, and polymeric implants to enhance its therapeutic index and reduce adverse effects.

[CONCLUSION] While etoposide is an effective topoisomerase II inhibitor with proven anticancer activity, its role in cervical cancer remains adjunctive rather than primary. Combination-based strategies and advanced drug-delivery systems hold promise for improving its clinical utility. Continued research is essential to overcome resistance and toxicity, potentially expanding the therapeutic relevance of etoposide in cervical cancer management.