Use of zoledronic acid therapy–associated severe hypophosphatemia to identify poor-prognosis patients with metastatic castration-resistant prostate cancer.

Abstract

58 Background: Zoledronic acid (ZOL) therapy is associated with severe (i.e., grade 3/4 according to CTCAEv4.0) hypocalcemia and hypophosphatemia in a subset of patients with metastatic castration-resistant prostate cancer (mCRPC) to bone. However, as opposed to the distinct clinical picture of hypocalcemia, the symptoms of hypophosphatemia are less pathognomonic. Furthermore, the rate of hypophosphatemia is not regularly reported. Methods: To characterize the rate and circumstances of severe hypophosphatemia in mCRPC patients undergoing ZOL therapy, we identified mCRPC patients receiving at least 3 doses of ZOL therapy at our Centre between 2004 and 03/2011. Patient demographics, disease and laboratory parameters were extracted by using the Oncology Symptom Control and Information Resource database, and by means of manual chart review. Results: 11 of 112 patients (10%) developed grade 3/4 hypophosphatemia (nadir) after 241±223 days (mean±SD) following the first dose of ZOL. Only one patient presented with concomitant severe hypocalcemia. Interestingly, the hypophosphatemia nadir coincided with rising PSA readings in 9 out of 10 informative patients. Furthermore, ZOL-associated severe hypophosphatemia identified mCRPC patients with worse outcome (time from CRPC diagnosis to death 628±317 days, versus 901±526 days in CRPC patients without severe ZOL-associated hypophosphatemia, p < 0.028). Conclusions: 10% of mCRPC patients undergoing ZOL therapy presented with grade 3/4 hypophosphatemia. While hypocalcemia usually occurs within the first 6 months of ZOL therapy, ZOL-associated severe hypophosphatemia is a relatively late event. It appears to occur at the time of disease progression and is associated with a poor outcome.