[Chronology of administration of cytotoxic drugs and combinations of chemotherapy with radiotherapy].

Contrarily to that which has been observed in some experimental tumors, the clinical data show that it is not possible to take advantage of the semi-synchronisation of tumor cells induced by the administration of cytotoxic drugs or ionizing radiations, either in combination chemotherapy or during the association between radiotherapy (RT) and chemotherapy (CT). The association of RT and CT has obtained excellent results in those human tumors which are both chemosensitive and radiosensitive such as lymphoma, testicular tumors, embryonal tumors, cancers of childhood. However, even in these favorable types of tumors, high doses of RT and CT are required, not significantly lower than those which are delivered when one of the two modalities is used alone. Therefore, the major problem is that of the possible cumulative toxicity of the two modalities. The toxicity appears to be maximum when the two modalities are administered concomitantly; it can be reduced in sequential administration when there is a sufficiently long interval between the various agents. However, sequential associations may cause long delay in the delivery of one of the two modalities and in rapidly growing tumors this delay might be detrimental. This is why an integrated alternating scheme was proposed in which short radiotherapy courses are interdigitated between the courses of chemotherapy, chemotherapy being administered with the conventional scheduling. Preliminary results of this alternating combination are discussed. In small cell carcinoma of the lung and non-Hodgkin lymphoma of poor histologic types, so far the results are promising.