Alkylating Agents Identified as Source of Second Cancers in Hodgkins

An investigation by Stanford researchers into three separate eras of Hodgkin's lymphoma clinical trials carried out between 1974 and 2003 indicates a likely culprit in treatment-induced secondary leukemia in these patients: the alkylating agent or agents that are part of combination chemotherapy. 

Dr. Ranjana H. Advani and colleagues, reporting their findings in the Journal of Clinical Oncology, wrote:

Successive generations of HL treatments at Stanford, specifically the Stanford V regimen, demonstrate a significantly lower risk of [therapy-related acute myeloid leukemia or myelodysplastic syndrome, or t-AML/MDS] without compromising efficacy, which was one of the important goals in the development of the latter regimen.

Trials carried out between 1974 and 1980 used MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) or PAVe (procarbazine, mechlorethamine, and vinblastine). t-AML/MDS = 5.7 percent

Trials carried out between 1981 and 1989 used MOPP or PAVe, or VBM (vinblastine, bleomycin, and methotrexate) or ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine). t-AML/MDS = 5.2 percent

Trials carried out between 1989 and 2003 used VBM with bleomycin reduced or Stanford V (mechlorethamine, doxorubicin, vinblastine, vincristine, bleomycin, etoposide, and prednisone). t-AML/MDS Incidence = 0.3 percent

The Stanford V regimen lowered the dose of nitrogen mustard by 75 to 83 percent and removed both procarbazine and melphalan. The subsequent lower exposure to these alkylating agents appeared to lower the incidence of secondary cancers. 

Noted Dr. Advani and colleagues:

Current ongoing adaptive strategies based on interim positron emission tomography imaging to evaluate early response to treatment may allow for selection of patients so that AA (alkylating agent) exposure can be limited to those with high-risk disease.

Source: Reuters Health