Abstract
While bisphosphonates are indicated for prevention of skeletal-related events, radionuclide
therapy is widely used for treatment of painful bone metastases. Combined radionuclide
therapy with bisphosphonates has demonstrated improved effectiveness in achieving
bone pain palliation in comparison to mono therapy with radionuclides or bisphosphonates
alone. However, there are conflicting reports as to whether bisphosphonates adversely
influence skeletal uptake of the bone-seeking radiotracers used for therapy. Recent
studies analyzing influence of Zoledronic acid on total bone uptake of Samarium-153
EDTMP (Sm-153 EDTMP) by measuring cumulative urinary activity of Sm-153 on baseline
study, as well as in combination with bisphosphonates (administrated 48 hours prior
to Sm-153) did not provide any statistically significant difference in urinary excretion
of Sm-153 between the two groups. It may be noted that the exact temporal sequence
of bisphosphonate administration vis a vis radionuclide therapy has not yet been studied.
One of the side effects of bisphosphonates is transient flare effect on bone pain.
Radionuclide therapy may also have similar side effect. Keeping in view the above
the current study was designed with the main objective of determining the exact timing
of bisphosphonate administration in patients receiving combined therapy so as to achieve
optimal efficacy of bone pain palliation. Ninety-three patients suffering from metastatic
bone pain who received combination therapy with Sm-153 oxabifore (an analog of Sm-153
EDTMP) and Zoledronic acid were divided into three groups according to the timing
of Zoledronic acid administration: Group I: 39 patients who received Zoledronic acid
7 or more days prior to Sm-153 oxabifore treatment; Group II: 32 patients who received
Zoledronic acid 48-72 hours prior to Sm-153 oxabifore treatment and Group III: 22
patients who received Zoledronic acid 7 days after Sm-153 oxabifore treatment. Sm-153
oxabifore was administered to all patients at the standard bone palliation dose of
37 MBq/kg body weight. All patients received Zoledronic acid before and after treatment
in standard dosage of 4 mg every 28 days. WB bone scan, CT, and MRI were performed
before treatment in all patients to exclude cord compression and vertebral fractures.
Pain scores and quality of life (QOL) measurements were recorded meticulously in all
patients. In groups I, II, and III, pain relief occurred in 10.4 ± 3.1 (Range = 5-15);
3.1 ± 1.1 (Range = 1-5) and 22 ± 5.1 (Range = 15-35) days, respectively, following
radionuclide therapy. There was statistically significant difference between pain
score in all groups before and after treatment as well as statistically significant
difference in time to pain relief onset between Group II and other groups of patients
(P < 0.0001). Based on our results we concluded that administration of Zoledronic acid
48-72 hours prior to Sm-153 oxabifore treatment helps in achieving better pain relief,
as well as at the shortest time interval from the start of therapy.
Keywords
Bone pain palliation - Sm-153 oxabifore - Zoledronic acid
