Ovarian cancer spheroid shrinkage following continuous exposure to cisplatin is a function of spheroid diameter

Most ovarian cancer patients present with advanced-stage disease, disseminated in the peritoneal cavity. Standard treatment involves surgical resection of all visible tumor, followed by delivery of systemic therapy. Patients with advanced-stage disease may be candidates for intraperitoneal (IP) chemotherapy following surgical debulking. Recent clinical trials have created controversy regarding the benefits of this approach. Previous clinical trials report that patients with microscopic residual disease respond best to IP therapy. The goal of this study was to determine the relationship between tumor size and the efficacy of continuous chemotherapy.

Small and large ovarian cancer spheroids (derived from UCI101 and A2780 cell lines) were exposed to short-term high (modeling an IP injection, "IP") or prolonged, low cisplatin concentrations (modeling an implanted device, "device"), which have been previously shown to be less toxic. Spheroid diameter was measured at various time points via image analysis and used to quantify tumor shrinkage over the course of treatment.

We show that "IP" doses more effectively shrink large spheroids when the same cumulative dose is administered with both treatments, but that both regimens similarly treat small spheroids. We also demonstrate that higher cumulative "device" doses are most effective at shrinking large spheroids.

These results support the hypothesis that intratumoral drug distribution following IP treatment is diffusion-controlled. An implanted device that continuously delivers low doses of IP chemotherapy would, therefore, be maximally effective against microscopic tumors.