Cure of mice bearing P388 leukemia by vincristine in combination with a calcium channel blocker.

Mice inoculated with P388 leukemia were treated initially with vincristine (VCR) at a dose of either 1.5 or 2.0 mg/kg. After 1 week, VCR alone (0.1 mg/kg) was given daily for ten treatments, but no mice were cured with this regimen. However, when the calcium channel blocker verapamil (75 mg/kg) was administered with VCR at 1.5 or 2.0 mg/kg, lifespans were prolonged and one of ten or six of ten mice were cured, respectively. As reported previously, verapamil renders less sensitive or resistant tumor cells susceptible to VCR by inhibiting the VCR efflux mechanism, especially in resistant cells. Therefore, verapamil in combination with VCR apparently can result in total cell kill under the conditions used.