Topoisomerases in the treatment of metastatic or recurrent squamous carcinoma of the head and neck

Abstract

Camptothecins are a class of antineoplastic agents that function via inhibition of topoisomerase I, a critical enzyme involved in DNA replication, transcription and chromosomal structure. Two topoisomerase I inhibitors, topotecan and irinotecan, have been developed and approved for the treatment of solid tumour malignancies. Because of their known activity, these and other camptothecins, such as 9-aminocamptothecin (9-AC), have been evaluated for the treatment of patients with recurrent or metastatic squamous carcinomas of the head and neck. Both 9-AC and topotecan failed to demonstrate consistent activity in this cohort of patients. Irinotecan demonstrated single-agent activity of 20% as first-line therapy for patients with metastatic or recurrent disease; however, efficacy was lacking as a second-line agent. Irinotecan is now being evaluated in combination regimens as first-line therapy for metastatic and recurrent disease. In addition, irinotecan is a potent radiation sensitising agent. Two Phase I trials using irinotecan-containing chemotherapy regimens with concurrent radiation in the primary treatment of head and neck cancer (HNC) patients have been reported. Clarification of the role of ir-inotecan in the treatment of HNC awaits further studies.

• head and neck cancer
• irinotecan
• radiotherapy
• topoisomerase I inhibitors
• topotecan