Scheduling of vincristine: drug accumulation and response of xenografts of childhood rhabdomyosarcoma determined by frequency of administration.

Vincristine (VCR) is an effective agent in the treatment of childhood rhabdomyosarcoma. Clinically, schedules differ in frequency of administration. To determine the influence of administration frequency, accumulation of VCR in xenografts of human rhabdomyosarcoma has been evaluated following administration of drug at 7- or 21-day intervals. Accumulation was estimated from initial uptake, retention of unchanged drug in tumor tissues, tumor sensitivity, and growth rate. Data suggested that scheduling VCR every 7 days would be more effective than every 21 days, due to more rapid accumulation to cytotoxic levels. The effect of scheduling was examined in two rhabdomyosarcoma xenografts, where in vivo responses were similar to those predicted based upon drug uptake, retention, and growth characteristics for the tumors. Scheduling VCR at 7-day intervals was clearly superior to administration at 21-day intervals in these models.