Basic principles of chemotherapy in the treatment of metastatic head and neck cancer

For patients who fail to achieve control of head and neck cancer with local therapy, chemotherapy offers limited benefit at present. Better understanding of the phenomena which surround tumor cell killing by active agents should allow for the rational design of more effective programs. For example, as tumors grow larger, many cells cease to engage in DNA synthesis and are refractory to drugs like methotrexate. In such a case, alkylating agents might be more effective. Tritiated thymidine uptake and nuclear DNA fluorescence studies can be exploited to analyze the kinetic and metabolic behavior of tumor cells, and are described. For animal models these studies have allowed the design of "kinetic" regimens of enhanced efficacy. Methotrexate, hydroxyurea, cyclophosphamide, vinblastine, and cis-platinum have appreciable antitumor activity in head and neck carcinoma. Combining active agents in a rational sequence could be facilitated by kinetic analysis of a patient's tumor, giving rise to specific regimens with more cytoreduction, less toxicity and resistance, and ultimately, better survival.