Treatment of Hodgkin's disease

The available data support the hypothesis proposed by Smithers that Hodgkin's disease appears to be a systemic disorder of the lymphatic system. Standard treatments have been developed that cure approximately 70% of all patients who present to most institutions. Physicians should know the treatment approaches before proceeding with staging, because intelligent use of the best available treatment often obviates the need for staging laparotomy. At present, it is best that either chemotherapy or radiotherapy be used alone, except in patients who have massive mediastinal disease and for whom combinations of radiotherapy and combination chemotherapy are superior. Despite the long series of clinical trials conducted over the past two decades, no combination of four drugs has improved the results obtained with the original mechlorethamine-vincristine-procarbazine-prednisone program, when it is given in sufficient doses. It has been assumed that drug resistance of a specific type was the major reason for treatment failure. Attempts by physicians to overcome drug resistance, using alternating cyclical non-cross-resistant combination chemotherapy, have thus far not proved this approach to be superior to the use of a four-drug combination in full doses, and call into question this approach to testing the Goldie-Coldman hypothesis. Dose intensity has been a poorly controlled variable in virtually all clinical trials in Hodgkin's disease, and inadequate dosing may be the prime reason for treatment failure. This point has been highlighted by recent excellent results with marrow-ablative, high-dose chemotherapy and autologous bone marrow transplantation support for patients with very advanced "drug-resistant" disease. Investigators are now attempting to improve dose intensity by using more concentrated versions of standard drug combinations with colony-stimulating factors for support.