The Chemotherapy/Radiation Balance in Advanced Hodgkin's Lymphoma: Overweight Which Side?
Authors: Patrice Carde
Journal: Journal of Clinical Oncology (2005)

Doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), without irradiation, is considered standard treatment for responding patients with advanced Hodgkin’s lymphoma (HL). Apart from escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), which is now being tested against ABVD in poor-prognosis HL, serious challengers are mechlorethamine, doxorubicin, vinblastine, vincristine, bleomycin, etoposide, and prednisone (Stanford V), and several multidrug regimens (MDRs), which are the subject of the two reports in this issue of the Journal of Clinical Oncology by Gobbi et al and Johnson et al. Through these articles, I wish to draw attention to the pertinent questions asked by the investigators regarding combined chemotherapy and irradiation for intermediate and advanced HL. Gobbi et al suggest that the chemotherapy part of the Stanford V treatment program, which is commonly used worldwide for advanced Hodgkin’s lymphoma, provides inferior results compared with those obtained by the much older ABVD regimen, and by mechlorethamine, lomustine, vindesine, melphalan, prednisone, epidoxorubicin, vincristine, procarbazine, vinblastine, bleomycin (MOPPEBVCAD), primarily used by the Italian Lymphoma Study group (IIL). Stanford V users can be reassured: the Stanford V used in this study was intentionally different from the original. The aim certainly was not to disadvantage one regimen against homemade protocols. The IIL intended to determine the best possible chemotherapy regimen for advanced HL patients and either to remove radiotherapy completely or to reduce drastically the irradiation fields. This was not achieved, due to the design of the study, in which the irradiation was different in each of the three randomized groups. Therefore, I recommend that the original Stanford V program—not a modified regimen—be used if outcomes reported by Horning are expected. The article by Gobbi et al aimed to investigate which of three chemotherapy regimens was superior by itself; that is, which regimen allowed a less frequent usage of irradiation, and when radiation was used, allowed a greater limitation of the irradiation field extent than in the original chemotherapy/radiotherapy combinations. The irradiation component was reduced intentionally, as compared with most irradiation modalities reported in the literature, although an incredibly broad spectrum of doses and fields are described as adjuvant treatment or consolidation for advanced disease. Indeed, in the study by Gobbi et al, no irradiation was allowed when a complete remission (CR) was achieved. When a partial remission (PR) or complete remission unconfirmed (CRu) was obtained, irradiation was administered only to those patients who had no more than two involved sites to irradiate; this meant also that a maximum of two involved sites could be irradiated (36 to 42 Gy), taking into account initial bulky site(s) plus residual CRu/PR disease. As a consequence, patients who otherwise would most require irradiation because of residual disease at the time of restaging after chemotherapy, especially those with few CRu/PR sites, were also, unfortunately, ineligible for irradiation. It should also be emphasized that chemotherapy was restricted to either 6 monthly cycles of ABVD or MOPPEBVCAD, or to 12 weeks of Stanford V chemotherapy, whereas many investigators recommend 8 months of standard-dose chemotherapy (ABVD). The IIL results show that the two 6-month regimens (when combined with different amounts of irradiation) fared better than the 3-month modified Stanford V regimen, in terms of failure-free survival (FFS), and for ABVD, in terms of overall survival (OS; P .04). For a correct interpretation of the data, it should be noted that the IIL study suffered from two drawbacks. The first was some imbalance in the distribution of the patients regarding patient numbers per arm and nodular sclerosis histology or bulky mediastinal disease. More importantly, the process that led to the decision of whether to administer radiation JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 23 NUMBER 36 DECEMBER 2