Perioperative Treatment With Zoledronic Acid in Patients With Resectable Pancreas Cancer

Cancer of the pancreas carries an ominous prognosis. The five-year overall survival rate of this malignancy is less than 5%. Chemotherapy with gemcitabine carries a response rate of approximately 25%. Resection offers the only potential for cure; however, even with resection, the great majority of patients will die with metastatic disease. Substantial improvements are needed in the treatment of this malignancy. Patients with this disease process have clearly developed a tolerance to their pancreatic tumor. This is evidenced by an increased number and activity immunosuppressive cells including MDSC and Treg in patients with pancreas cancer. An intervention that inhibits this population of MDSC and Treg may be highly useful in the treatment of this disease process. A novel treatment of pancreas cancer, in this setting, would be to deplete circulating and tumor-associated immunosuppressive cells prior to resection. This would facilitate the host to mount a greater immune response against the tumor. The eventual goal would be to combine neoadjuvant zoledronic acid with gemcitabine, another agent which synergizes with zoledronic acid to target MDSC. When combined with current adjuvant chemoradiation, the use of zoledronic acid in the neoadjuvant and adjuvant setting, it is hoped that the patient could mount a greater immune response leading to increased overall survival through the prevention of local disease and distant metastasis.