Solid tumor models for the assessment of different treatment modalities: XXV. Comparison of the effect of one radiation fraction per day with multiple fractions per day (MFD) given either continuously or intermittently on tumor response and normal tissue reaction.

A series of experimental studies has been carried out to assess the relationship between the effectiveness of tumor control, normal tissue reaction and median survival following different radiation fractionation schedules on the solid tumor model 3924A in the ACI rat. The total radiation dose of 7500 rad and the dose per fraction of 250 rad were held constant. Tumor control and life expectancy improved with 250 rad given continuously as multiple fractions per day (MFD) (1, 2 and 3 fractions per day over 30-, 15- and 10-day periods, respectively). However, the maximum acute skin reaction surrounding the tumor was greater for MFD given continuously than for single daily fractions. We have also completed studies of the therapeutic effectiveness of MFD given intermittently at 11-day intervals. Tumor control following MFD given intermittently was comparable to that following the daily fraction schedule given continuously, and the normal tissue reaction was acceptable at a total radiation dose of 7500 rad. Experimental and clinical results in head and neck cancer indicate that large total radiation doses in the order of 7000 rad given as continuous MFD are associated with unacceptable normal tissue reaction. However, these clinical and experimental results also indicate that large total radiation doses can be given as MFD intermittently and effectively used in cancer management. The marked superiority of alternating chemotherapy and radiotherapy in obtaining a tumor cure rate of greater than or equal to 50% in our experimental system and the superiority of alternating chemotherapy and radiotherapy in extensive Hodgkin's disease (complete response rate--87%) over chemotherapy alone, radiotherapy alone, or the two modalities given together or as split course provides the clinical and experimental basis for the development of more effective protocols in the treatment of tumors responsive to chemotherapy and radiotherapy. A complete response rate of 78% in patients with head and neck cancer, and a complete response rate of 89% in patients with limited small cell carcinoma of the lung using alternating chemotherapy and radiotherapy indicate that it is now possible to proceed rapidly in clinical protocol design for these two additional tumors responsive to both chemotherapy and radiotherapy.