Are Alkylating Agents a Necessary Component in the Therapy of Hodgkin's Disease

Abstract

Management of early stages of Hodgkin's disease requires development of treatment programs that are nominally toxic, with a low likelihood of sterility and secondary malignancies, both associated with alkylating agents. Although patients with laparotomy-staged disease without B symptoms or large mediastinal masses have good results when treated with radiotherapy alone, patients with adverse features need chemotherapy for optimal disease-free survival results. MOPP and its variants have been studied extensively for adjuvant therapy of patients with early staged disease but are associated with the development of secondary malignancies, including acute leukemia and solid tumors. ABVD has been compared with MOPP in combination with radiation therapy for patients with stages IIB and IIIB. and ABVD is not associated with a high risk of acute leukemia; however, cardiac and pulmonary toxicities have been reported, and there may be long term complications following ABVD in combined modality programs.

In 1988, we developed NOVP [mitoxantrone (Novantrone^TM), vincristine, vinblastine, prednisone], designed as adjuvant chemotherapy to treat patients with clinically staged I-II Hodgkin's disease who had unfavorable features, including B symptoms, large mediastinal masses, and hilar lymph node involvement. We also included patients with peripheral masses ≥ 10 cms and those with stage III disease. In the second phase of this study, we treated patients without adverse features, in order to avoid laparotomy. The treatment plan included three cycles of NOVP, followed by radiotherapy to the mantle and the abdomen, with fields depending upon disease presentation. Patients with large mediastinal masses or hilar involvement also received low dose lung radiotherapy. With a median follow-up of 18 months, 99 patients have received NOVP and radiotherapy. Ninety-seven percent entered CR and ten patients have experienced progressive disease.

There are many reasonable choices of treatment for patients with Hodgkin's disease. However, those with adverse prognostic features need combined modality therapy, even when treatment includes prolonged intensive chemotherapy. Options for patients without large mediastinal masses or other adverse prognostic factors might still include staging by laparotomy followed by radiation therapy. However, treatment options including combined modality therapy and radiation therapy without laparotomy are also reasonable for these favorable groups, especially when chemotherapy regimens utilized are associated with low toxicity.

Key Words:

• Chemotherapy
• Hodgkin's disease
• clinical staging