Sequencing of drugs and radiation. The integrated alternating regimen

The association of radiotherapy (RT) and chemotherapy (CT) constitutes one of the main avenues for research in therapeutic oncology. This association has two aims: (1) increase in control rate of primary tumor (this requires either the potentiation of one of the two modalities by the other or the additivity of their effect on tumor cells without a parallel increase in the toxic effects on critical normal tissues); (2) spatial cooperation (RT being used for the control of the primary tumor or of the sanctuaries, and CT for the control of the disseminated disease). In these two strategies, RT and CT should be given up to full doses in order to be effective. The main risk is an increase in the number and severity of the early and late side effects. To circumvent this problem, two possibilities are being explored: (1) use of drugs without serious toxic effects on those critical tissues which are included in the irradiated volume; and (2) avoidance of concomitant administration and introduction of a sufficiently long-time gap between the completion of one modality and initiation of the other. However, in such sequential treatment, a delay of CT until after the completion of RT, or an interruption of CT cycle during the course of RT, allows the occult metastases to increase in size; a similar delay in initiation of RT is also detrimental, as drugs are often not effective on bulky tumors. Moreover, under CT, the cells which are resistant to the cytotoxic drugs may disseminate and initiate chemoresistant metastases. Taking these disadvantages into account, a treatment protocol was proposed in 1980 in which CT and RT are given alternately, without undue delay. Chemotherapy is started with the usual scheduling of one cycle every month. Radiotherapy courses are interdigitated between CT cycles. Each course is initiated 1 week after interrupting CT and continued until 1 week before beginning the subsequent cycle of chemotherapy, and so on until completion of RT. Such split-course RT should have an effect on a tumor comparable to that of a conventional fractionation. This protocol has been used on 24 patients with non-Hodgkin's lymphoma (NHL) of diffuse histology, and 63 patients with small cell carcinoma of the lung. The 2-year relapse-free survivals are promising (in clinical stage II NHL of diffuse histology, 75%; and in small cell lung carcinomas, 33%).(ABSTRACT TRUNCATED AT 400 WORDS)