Multidrug Resistance Foiled By Novartis, Vertex Drugs

Drug resistance in tumor cells is a primary cause of treatment failurein many types of cancer, and often shares a common mechanism known as multidrug resistance. Now, new data from trials of Novartis' PSC-833 and Vertex' VX-710 suggest that this resistance can be countermanded, restoring the efficacy of paclitaxel-based treatment.

MDR is problematic because tumors develop cross-resistance to many drugs after exposure to only one. The underlying mechanism is that tumors become efficient at pumping anticancer drugs out of cells, a process associated with P-glycoprotein (also known as MDR1) and multidrug resistance-associated protein (MRP).

Abbie Fields of the Albert Einstein College of Medicine in New York reported interim data from a study in which PSC-833 was given in combination with paclitaxel in patients with paclitaxel-refractory advanced ovarian cancer. At the time of the presentation, 52 patients had received a total of 198 cycles of oral PSC-833 (5mg/kg four-times daily on days one to three) as well as paclitaxel (70mg/m2 three-hour infusion) every 21 days. The patients had received a median of four prior chemotherapeutic regimens, and were therefore heavily pretreated. Despite this, Dr Fields reported that responses were observed in four patients, and an additional seven had significant reductions in blood tumor marker values (CA-125).