Myelodysplastic syndrome and acute nonlymphocytic leukemia secondary to mitolactol treatment in patients with breast cancer

Abstract

One thousand four hundred sixty patients with 2,590 patient-years of follow-up were treated on 15 protocols for metastatic breast cancer with dibromodulcitol (mitolactol; DBD)-containing regimens since 1976. Twenty-three patients developed myelodysplastic syndrome (MDS) and/or acute nonlymphocytic leukemia (ANLL). The overall risk of developing MDS or ANLL per person is 1.6%. In patients who had received more than 16,000 mg of DBD the risk per person is 6%, and in the high-dose subsets of patients who received no prior radiation or alkylator therapy, it is 7.9%. The risk per person increases to a maximum by 30 to 36 months (5.3%). The high risk was seen despite a study population of metastatic breast cancer patients with a median survival of 16 months. This analysis strongly suggests that DBD is one of the most potent of the reported leukemogenic-inducing agents. Further use of this drug in both the adjuvant and metastatic situation should be reconsidered.