Reviews in Gynaecological Practice 2 (2002) 29–34 Review The role of topoisomerase inhibitors in gynaecological oncology Geoffrey D. Hall ∗ , Timothy J. Perren Cancer Research UK Clinical Centre in Leeds, St. James’s University Hospital, Beckett Street, Leeds LS9 7TF, UK Abstract The topoisomerase inhibitors represent a distinct class of chemotherapy drugs with a distinct and highly specific mechanism of action. Through an inhibition of the nuclear enzymes topoisomerase I or II they inhibit mechanisms which allow normal DNA replication to occur, leading ultimately to cell death. The role of the topoisomerase inhibitors has been assessed in a number of gynaecological malignancies. Topotecan and oral etoposide have both been shown to have efficacy as single agents in patients with ovarian cancer whose disease has relapsed following platinum and paclitaxel chemotherapy. Randomised controlled trials which incorporate topotecan into first-line therapy for both ovarian and cervical carcinoma are underway. Their role in other gynaecological settings is less clear and continues to be defined in clinical studies. © 2002 Elsevier Science B.V. All rights reserved. Keywords: Chemotherapy; Topoisomerase inhibitors; Ovarian cancer; Carcinoma of the cervix 1. Introduction The failure of standard chemotherapy to cure most pa- tients with cancer drives the search for new, more effective drugs. The topoisomerase inhibitors are a relatively new class of chemotherapy drugs with a distinct and highly specific mode of action. Their role in the management of women with gynaecological malignancies is currently being assessed. This review will focus principally on the drugs topotecan, irinotecan and etoposide and their use in the management of epithelial ovarian carcinoma and cervical carcinoma. 2. Current role of chemotherapy in gynaecological malignancies 2.1. Epithelial ovarian cancer Recent clinical trials have defined the standard of care for chemotherapy following surgery in epithelial ovarian cancer as a platinum agent (cisplatin or carboplatin) in combina- tion with a taxane (paclitaxel or docetaxel) [1–3]. These clinical trials have led the National Institute of Clinical ∗ Corresponding author. Tel.: +44-113-206-7045; fax: +44-113-242-9886. E-mail address: g.hall@leeds.ac.uk (G.D. Hall). Excellence (NICE) to publish UK clinical guidelines in which “paclitaxel in combination with a platinum therapy (cisplatin or carboplatin) should be the standard initial ther- apy for patients with ovarian cancer following surgery.” Subsequent relapse occurs in the majority of patients and subsequent therapy is guided by the duration of response. If more than 6 months have passed since treatment, the disease is likely to remain platinum-sensitive and further platinum-based chemotherapy is likely to be beneficial. If the disease has failed to respond to platinum chemotherapy or relapsed within 6 months, other chemotherapy agents are indicated. 2.2. Carcinoma of the cervix Two clear indications exist for chemotherapy in the man- agement of cervical carcinoma. For those patients who require radiotherapy, concurrent cisplatin-based chemother- apy has recently been shown to reduce the risk of death by 30–50% in a number of randomised phase III trials [4–7]. In locally recurrent or metastatic disease, chemotherapy is less well defined. Many agents have been assessed with overall response rates of 15–35%. The combination of bleomycin, ifosfamide and cisplatin (BIP) has reported response rates of up to 69% [8]. Although the topoisomerase inhibitors do not constitute standard chemotherapy for any gynaecological malignancy, their activity and indication is actively being assessed in a variety of clinical trials. 1471-7697/02/$ – see front matter © 2002 Elsevier Science B.V. All rights reserved. PII:S1471-7697(02)00004-7