Radiotherapy and chemotherapy in combined clinical trials: Problems and promise

Abstract

The recent clinical experience with combined radiotherapy and chemotherapy has been reviewed. Trials using these two modalities together have increased greatly since initial studies in Wilms tumor and in acute leukemia. Both unusual toxicities and therapeutic synergisms have been uncovered. The aim of this combined therapy is that of either local “radiopotentiation” or chemotherapeutic control outside the radiation field, or both. The sequence, dose, and schedule relationship has been empirically established and exploration for optimal sequences has been minimal. Nevertheless, great experience has accrued in hematologic malignancies. In addition, an important application of combined modality therapy has been the treatment of childhood solid tumors, with striking successes in Wilms tumor, Ewing's sarcoma and rhabdomyosarcoma. Many trials have also begun in lung cancer (small cell carcinoma), breast cancer, gynecologic and gastrointestinal malignancies, epidermoid cancer of various sites in the head and neck, and central nervous system tumors. However, the list of complications from combined treatment is also growing. Enhancement of hematologic toxicities and the predisposition to higher secondary neoplasms, particularly acute leukemia, have been known for some time, although they are receiving increasing attention as combined therapy extends to more favorable groups of patients. Newly recognized complications are the unique development of the accelerated bleomycin induced pulmonary fibrosis with preceding mediastinal irradiation, the finding of anthracycline cardiomyopathy potentiated by preceding cardiac irradiation, and the leukoencephalopathy following methotrexate and cranial irradiation. The therapeutic promise of combined modality treatment has hardly begun to be explored. Experimental study of radiation-chemotherapy interactions constitutes an important area of investigation.