Feasibility of different combinations of chemotherapy (6 MOPP) plus radiotherapy in Hodgkin's disease

During a preliminary clinical experience (1973-1977) we experimented three different sequences in associating 6 MOPP cycles (CT) with radiotherapy (RT) for the treatment of stage II and III Hodgkin's disease. A total of 55 consecutive previously untreated patients can be estimated to contribute in defining feasibility, immediate results and toxicity of the combined treatment. In this group of patients RT preceded CT in 20 cases (RT-6 MOPP), the opposite sequence (6 MOPP-RT) was preferred in 16 cases, whilst a split-course CT fitting in the RT (3 MOPP-RT-3 MOPP) was employed in 19 cases. Except for the sequence used with respect to irradiation, the CT was carried out in all the cases according to the classical scheme proposed by De Vita et al. (11). RT was effected with 60Co-teletherapy and a wide field or segmental sequential fields, having variable extension depending on the stage ("extended nodal irradiation" for stage II and III cases with lymph node involvement not below L3; "total nodal irradiation" for the remaining cases in stage III). The programmed doses were 45.0 Gy to the involved areas and 40.0 Gy to the clinically uninvolved regions for the RT-6 MOPP and 6 MOPP-RT groups. Doses of 35.0/30.0 Gy were planned for the 3 MOPP-RT-3 MOPP group. The three different groups are not homogeneous with regard to certain important clinical and pathological characteristics; in fact, a higher quota of stage III patients, with systemic symptoms and spleen positivity is present in the 6 MOPP-RT and 3 MOPP-RT-3 MOPP groups. The combined treatment has achieved a complete clinical remission in 18/20 patients in the RT-6 MOPP group (90.0%), in 12/16 patients of the 6 MOPP-RT group (75.0%), and in 17/19 cases in the 3 MOPP-RT-3 MOPP "sandwich" combination (89.5%). The average overall duration of the treatment was 48 weeks for the sandwich combination, 50 weeks for the RT-6 MOPP group, and 56 weeks for the 6 MOPP-RT association. As regards the sandwich combination, both CT and RT took a reasonable length of time to complete. On the contrary, both the medical treatment and irradiation required an excessively long time and were not well tolerated when preceded by either RT or CT in full doses. In particular, myelosuppression was less acute and prolonged in the 3 MOPP-RT-3 MOPP group, whereas the actual doses of CT and RT were higher than those which can be reached with respect to other groups. Three preliminary cycles of CT considerably reduce the target volumes and complications arising from RT. The first CT time gave an objective response greater than 50% in 9/9 cases of the 3 MOPP-RT-3-MOPP group with mediastinal involvement. In this group, rather considerable pulmonary complications were observed in 3/9 patients (33.3%) with respect to the 40% found for the 6 MOPP-RT group (2/5 cases) and the 67.7% for the RT-6 MOPP group (6/9 cases).