Faculty Bibliography

Administration of a number of cytotoxic agents has been associated with interstitial pneumonitis, alveolitis and pulmonary fibrosis. Some (bleomycin, busulfan, methotrexate) are well known to cause this problem, and others (carmustine, semustine, zinostatin, mitomycin, and chlorambucil) have only recently been recognized to do so. We review and update the available information about this form of drug toxicity. Interaction between these drugs and thoracic radiation or high oxygen fractions in inspired air has produced pneumonitis at doses lower than when the drug is used alone. Synergism between the drugs themselves when given concurrently also produces pulmonary toxicity at lower doses. With some drugs and in some patients steroids will diminish the pulmonary abnormalities, but death from hypoxia is a frequent outcome. Since early recognition of the problem and withdrawal of the injurious agent is the best treatment, physician awareness of and alertness to this toxicity and its relative risk is most important. The discovery of analogs of bleomycin with a better therapeutic index, specifically reducing pulmonary damage, is one of the goals of current cancer drug development.

Early studies of intraarterial chemotherapy in patients with squamous carcinoma of the head and neck resulted in tumor response rates similar to those achieved with systemic chemotherapy, but which were associated with unacceptable morbidity. The results of recent clinical trials suggest that intraarterial chemotherapy can achieve higher response rates than previously reported and that the frequency of morbid complications can be reduced. A summary of the discussions which took place at a recent NCI-OSITC Workshop on Intraarterial Chemotherapy of Head and Neck Cancer is presented. New therapeutic strategies and improved treatment techniques provide the rationale for a reevaluation of intraarterial chemotherapy in patients with head and neck cancer.

Chemotherapy of head and neck cancer has recently been receiving increasing attention as a treatment modality. The basis for this interest has been the availability of at least three agents with reproducible antitumor activity: methotrexate, bleomycin, and cisplatinum (diamminedichloroplatinum). These agents alone or in combination have been demonstrated to be of palliative value in patients whose disease recurs or is too advanced for other therapeutic modalities. Although the multiple drug regimens used have not been curative, their relative effectiveness has raised hopes that, in combination with other modalities, they may lead to improvements in survival and in local control in earlier stages of disease. In addition, as a result of multimodality approaches, it is hoped that it may be possible to identify the role of chemotherapy and specific agents in the treatment of various sites of origin of these tumors. The interaction of chemotherapy and radiation--and the use of intraarterial chemotherapy--fall beyond the scope of this review but constitute another important aspect for investigation in the treatment of these malignancies.