Can verapamil induce second response in patients refractory to vincristine?

Verapamil (240 mg daily orally) was tested in a phase II trial to restore vincristine sensitivity in 9 patients with myeloma, chronic lymphatic leukemia and immunocytoma. These tumors were selected because treatment response and tumor progression can easily be ascertained with the help of electrophoresis and marrow studies, blood counts and lymph node examination. All patients were clinically refractory to vincristine-cytoxan-prednisolone combinations, to which adriamycin had been added in 2 patients. One patient was refractory to adriamycin, VM 26, and prednisone. In 2/9 patients a side effect-free second response lasting 5-10 months was observed, with a doubtful response in two additional patients. It is suggested that occasional clinical responses can be seen, despite the fact that in vitro the mean verapamil concentration required to affect vincristine efflux from malignant lymphocytes in 5 mumols/1 and the mean in vivo serum concentration only 1 mumole. Hypothetically, the clinical response can be explained by an overlapping in some patients of an unusually high serum concentration with an unusually low verapamil requirement.