Management of recurrent head and neck cancer: recent progress and future directions.

The incidence of squamous cell carcinoma of the head and neck (SCCHN) is on the rise in the US despite a drop in cigarette smoking rates. Much of this rise is due to the increasing incidence of SCCHN attributable to human papillomavirus (HPV). HPV-related SCCHN has a high cure rate, which contributes to the stable death rates despite the increased incidence. Up to half of patients with SCCHN will develop recurrence. For these patients, the first clinical decision is whether the recurrence is potentially treatable for cure, or is incurable. For those deemed potentially curable, surgical or radiation-based therapies, or both, are undertaken. For those who have incurable recurrences, the goals are palliation and possibly prolongation of life - average survivals are in the range of 6-12 months depending on the type of recurrence and other factors. Several chemotherapy drugs are active in SCCHN, most notably the platinum compounds, taxanes, fluorouracil (5-FU), methotrexate and cetuximab. Approximately 10-25% of patients will respond to treatment with one of these drugs. The response rate is higher for combinations such as a platinum plus a taxane, a platinum plus 5-FU, a combination of the three, or one of more of these drugs plus cetuximab. Combination chemotherapy has not been shown to prolong survival over single-agent therapy, with the exception of the addition of cetuximab to a platinum and 5-FU combination. A number of orally bioavailable tyrosine kinase inhibitors have been tested or are undergoing trials in SCCHN. None of these has as yet been shown to be more effective than the currently available drugs. For patients with recurrences who are undergoing active therapy, and especially for those for whom further therapy is no longer appropriate or is declined, strict attention is necessary to palliation of pain, oral and airway issues, and to nutrition, speech, and social and psychological issues.