Prospectives in head and neck oncology

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Abstract
The knowledge that the sensitivity of a tumor to radiotherapy and chemotherapy relates to its cytokinetics led to the adoption of a treatment protocol which it is hoped will expose the tumor cells in a most sensitive phase to a particular form of treatment. An attempt was made to synchronize tumor cells with vincristine for subsequent destruction by bleomycin given 6 h later. After an arbitrary 18 h interval which may approximate the G1 interval in human squamous carcinomas, cells that escaped the effects of vincristine and bleomycin might be destroyed by a cycle specific drug such as cyclophosphamide. This is given as a single large dose and may be omitted in debilitated and elderly patients. Methotrexate is then given as an i.v. infusion over a 24 h period. This prolonged infusion may increase the percentage of cells exposed to the drug during their sensitive S phase. Folinic acid is given for 36 h following the methotrexate infusion to protect the patient''s normal stem cell system. Initial radiotherapy in doses of 1500-2000 rads, given over 10 days, may be used to increase the percentage of proliferating cells and radiotherapy may be repeated in the intervals between courses of chemotherapy. A repeated constant cell kill fraction may be achieved in the entire tumor cell population. It is difficult to decide when chemotherapy should stop, as there is no test to indicate the persistence of 0.01% residual viable tumor cells. Maintenance chemotherapy could be continued with benefit for as long as 2 yr. A small mmber of cancer cells may remain viable because of pharmacological barriers, inherent or acquired drug resistance or because environmental factors provided protection against the effects of radiotherapy and chemotherapy. For whatever reason the elimination of this small residual tumor cell population is likely to be successfully managed by a competent immunological system.