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 irinotecan in the treatment of HNC awaits further studies.