Epipodophyllotoxin and Cisplatin on Continuous Infusion Schedules

The Epipodophyllotoxins, VP16-213 and VM26, and the heavy metal cytotoxic agents, Cisplatin and its analogs, Spirogermanium and Gallium, represent two classes of agents which in clinical trials are traditionally delivered on an intermittent bolus schedule. Extensive clinical reviews of the clinical trials employing these agents have not emphasized the continuous infusion schedule (1–3). In fact, the thrust has been directed toward maximizing the dose of delivery on an intermittent bolus schedule to increase therapeutic effects (4,5). Such has been the traditional approach to cancer chemotherapy in general based upon the concept of the dose-response relationship developed in experimental tumor systems and upon practical issues involving patient convenience and outpatient delivery. Such precepts have been the basic tenets for the day one and eight schedule for such programs as MOPP chemotherapy for Hodgkin’s disease and the CMF program for breast cancer.