Combination Re-186-HEDP and cisplatin supra-additive treatment effects in prostate cancer cells

Radionuclide therapy has proven to be an efficacious palliative treatment f or metastatic prostate cancer. Its potential therapeutic possibilities may be substantially increased by combining it with effective radiosensitizing drugs. Methods: This study explores the radiosensitizing properties of cisp latin when combined with Re-186-fabeled hydroxyethylidene diphosphonate (HE DP) in the treatment of R3327-MATLyLu prostate cancer cells in vitro. A con comitant incubation during 4 d, combining various concentrations of cisplat in (0, 0.42, 0.83 and 1.67 mu mol/L) and Re-186-HEDP (0, 1.84 and 3.69 MBq/ mL [0, 50 and 100 mu Ci/mL, respectively]) was followed by the determinatio n of the cell numbers surviving and the replating of these cells in semisol id agar. Results: The surviving fraction of clonogenic tumor cells after co mbination treatment clearly showed synergism when analyzed by a panel of th ree different published analytical methods. In addition, analysis of varian ce demonstrated a significant interaction between radionuclide therapy and cisplatin-based chemotherapy (P < 0.001). Treatment with Re-186-HED and cis platin by sequential incubation yielded similar, but never superior results . Conclusion: It is concluded that radionuclide therapy in combination with cisplatin is able, in principle, to improve therapeutic success rate in me tastatic prostate cancer in a more than additive way.