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Combined use of zoledronic acid and 153Sm-EDTMP in hormone-refractory prostate cancer patients with bone metastases

By M.G.E.H. Lam, Amel Dahmane, W.H.M. Stevens, Peter P. van Rijk, J.M.H. de Klerk and Bernard A. Zonnenberg


Purpose: 153Sm-ethylenediaminetetramethylenephosphonic\ud acid (EDTMP; Quadramet®) is indicated for the treatment of\ud painful bone metastases, whereas zoledronic acid (Zometa®)\ud is indicated for the prevention of skeletal complications.\ud Because of the different therapeutic effects, combining the\ud treatments may be beneficial. Both, however, accumulate in\ud areas with increased osteoblastic activity. Possible drug\ud interactions were investigated.\ud Methods: Patients with hormone-refractory prostate cancer\ud were treated with 18.5 MBq/kg 153Sm-EDTMP in weeks 1\ud and 3 and with 37 MBq/kg in week 15. Treatment with 4 mg\ud zoledronic acid began in week 3 and continued every\ud 4 weeks through week 23. In weeks 3 and 15, zoledronic\ud acid was administered 2 days before 153Sm-EDTMP\ud treatment. Urine was collected 48 h after injection of\ud 153Sm-EDTMP, and whole-body images were obtained 6,\ud 24 and 48 h post-injection. The effect of zoledronic acid on\ud total bone uptake of 153Sm-EDTMP was measured indirectly\ud by the cumulative activity excreted in the urine in weeks 1, 3\ud and 15. Biodistribution, safety, tolerability and effect on\ud prostate-specific antigen level were also studied.\ud Results: The urinary excretion in week 3 divided by the\ud urinary excretion in week 1 (baseline) times 100% was\ud mean 98.4±11.6% (median 96.2%). From week 1 to 15,\ud after four zoledronic acid treatments, the mean ratio was\ud 101.9±10.7% (median 101.8%). Bioequivalence could be\ud concluded by using a two-sample t test for both perprotocol\ud (n=13) and full-analysis sets (n=18). Toxicity was\ud comparable to of monotherapy with 153Sm-EDTMP.\ud Conclusion: Zoledronic acid treatment does not influence\ud 153Sm-EDTMP skeletal uptake. Combined treatment is\ud feasible and safe

Topics: Geneeskunde, Bone metastases, Pain, Samarium, Zoledronic acid, Nuclear therapy
Year: 2008
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