Concurrent Radiation Chemotherapy for Locally Advanced Head and Neck Carcinoma: Are We Addressing Burning Subjects?
11/30/2004 Houston, TX K. Kian Ang The University of Texas M.D. Anderson Cancer Center, Houston, TX Improving the outcome for patients with locally advanced head and neck carcinomas (HNC) by rational modification of radiation fractionation regimens or combinations of radiation with chemotherapy has been the subject of intensive clinical investigations for more than three decades. The two prototypes of biologically sound-altered radiation fractionation regimens are hyperfractionation and accelerated fractionation.1 Hyperfractionation was based on preferential sparing of late-responding tissues when the radiation dose per fraction is reduced. Accelerated fractionation regimens emerged through the recognition that tumor clonogen proliferation occurring during radiotherapy has a detrimental effect on outcome. Results of large randomized trials addressing the optimization of radiation fractionation collectively show that a number of biologically sound altered fractionation schedules improve the locoregional (LR) control rate on the order of 10% to 15%, but have only a modest impact on overall survival. Although several altered fractionation regimens consistently induce more severe acute mucositis than standard 7-week radiotherapy, the general consensus is that late toxicities are not appreciably increased. Scores of clinical trials testing combined-modality therapy have also been published. Meta-analyses of studies completed before 1995 reveal that cytotoxic agents given before or after surgery or radiation do not significantly improve the therapeutic outcome over LR treatment alone. In contrast, chemotherapy given concurrently with radiation improves 2- and 5-year overall survival rates by 8%. Although a variety of cytotoxic agents have been studied, cisplatin is the most extensively investigated, and will be the [...]