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