Overview of platinum chemotherapy in head and neck cancer

Platinum-based chemotherapy has been used to treat head and neck cancer for approximately 15 years. For patients with recurrent disease, cisplatin/5-fluorouracil (5-FU) and carboplatin/5-FU combinations have proved superior to single agents in producing higher overall response rates. However, survival rates are not substantially affected, indicating a need to identify alternative new agents with activity. Newly diagnosed patients with advanced stages III and IV disease generally have a poor prognosis. The most common site of failure and cause of death is locoregional recurrence. To improve survival and alter patterns of failure in this population, platinum-based chemotherapy regimens have been combined with surgery or radiotherapy as initial curative treatment. Cisplatin/5-FU chemotherapy in this setting is effective in significantly reducing the incidence of distant metastases as shown in several randomized trials. The sole indication for induction chemotherapy in patients with advanced laryngeal cancer is as an alternative to laryngectomy. The Department of Veterans Affairs Laryngeal Cancer Study Group trial demonstrated no significant differences in survival in patients who received induction cisplatin/5-FU and radiotherapy or total laryngectomy and postoperative radiotherapy. An alternative approach utilizing cisplatin or carboplatin alone or combined with 5-FU, administered simultaneously with radiotherapy, is under investigation. Pilot data suggest that this approach may be more effective in improving locoregional control and hence survival. Three intergroup prospective, randomized trials currently are comparing sequential chemoradiotherapy, simultaneous chemoradiotherapy, and standard radiotherapy alone in advanced nasopharyngeal cancer, advanced resectable laryngeal cancer, and unresectable cancers from other sites in the head and neck. These trials are designed to definitively address questions of treatment modality sequence and its impact on pattern of failure and survival.