Oral chemotherapy in head and neck cancer.

Chemotherapy plays an important role in the palliative treatment of head and neck cancer and in the neoadjuvant setting for larynx preservation. Together with concomitant radiotherapy, chemotherapy is also important for the curative and palliative therapy of unresectable head and neck cancer. Although issues relating to anatomical and pharmacological constraints exist, new orally administered drugs, as well as oral substitutes for the currently utilised intravenous drugs, would be extremely desirable in each of these situations. Of the oral fluorinated pyrimidines, tegafur/uracil (UFT) alone produced a complete response rate of 19%, and combination therapy of tegafur/uracil or tegafur with cisplatin or carboplatin has produced response rates comparable to those seen with intravenous fluorouracil (5-FU) plus cisplatin or carboplatin. An initial dose-finding study of 5-FU plus eniluracil indicates that further studies are warranted. The ribonuclease reductase inhibitor hydroxycarbamide (hydroxyurea) has been extensively studied in combination with 5-FU and radiotherapy (the FHX regimen) in patients with head and neck cancer, with high rates of local control. Improvement in locoregional and distant control rates may occur when FHX is combined with additional systemically active agents (cisplatin then paclitaxel) and hyperfractionated radiotherapy is used. Good candidate drugs for head and neck cancer include BMS-182751, an oral platinum complex, and capecitabine and S-1, other oral fluoropyrimidines. In addition, methotrexate and cyclophosphamide both have some activity in head and neck cancer and deserve further investigation.