A randomized controlled trial to compare the efficacy of bisphosphonates in the management of painful bone metastasis

Abstract

Introduction:The prospective interventional single-institution randomized control study was carried out to compare the pain relieving efficacy among different bisphosphonates at the cost of incidence of skeletal-related events (SRE).Materials and Methods:During June 2008 and May 2011, 256 patients with painful bone metastasis in solid tumors with a pain score of at least 5 were randomized into three arms: zoledronic acid (4 mg, i.v.), ibandronate (6 mg, i.v.) and pamidronate (90 mg, i.v.). Radiation was given to all patients, either 800 cGy single fraction or 20 Gy in five fractions. The ANOVA test was used for analysis. The Pearson test was used to correlate pain scores with proportions of responders as statistical estimation of pain relief.Results:With a mean baseline pain score of 6.5 ± 1.2, there was no difference in pain scores among the three treatment arms, assessed at 3 months and at the end of the study. However, the pain scores at 6 months were statistically reduced in zoledronic acid-receiving patients (1.5 ± 0.4) unlike the scores in patients receiving ibandronate (3.1 ± 0.5) and pamidronate (2.3 ± 0.4), with a P-value of 0.024. The response was statistically significant at 6 months (0.039) and at the end of the study (0.023), in favor of zoledronic acid. Pearson's correlation demonstrated a statistically significant positive correlation between pain scores and response rates. There were no statistical differences in the narcotic scores among the treatment arms during the study period. The overall duration of pain relief was not different in any of treatment arms. The time of detection of hypercalcemia was no different; however, the incidence of hypercalcemia was significantly less in the zoledronic acid arm (28.3%) against 44.6% and 50% in ibandronate and pamidronate arms, respectively, with a P-value of 0.041.Conclusion:The use of bisphosphonates for 6 months or more results in a statistical significant improvement in bone pain, more so with zoledronic acid. Hypercalcemia, an SRE, was significantly less in the zoledronic acid arm.

Bone Metastases in Well-to-Moderately Differentiated Neuroendocrine Tumors

“…For example, radiation therapy has been found to alleviate metastatic bone pain 4 ; bisphosphonates have been associated with decreased rates of spinal cord compression, fractures, and bone pain 5,6 ; and the RANK-ligand inhibitor, denosumab, has been associated with fewer pathologic fractures. For example, radiation therapy has been found to alleviate metastatic bone pain 4 ; bisphosphonates have been associated with decreased rates of spinal cord compression, fractures, and bone pain 5,6 ; and the RANK-ligand inhibitor, denosumab, has been associated with fewer pathologic fractures.…”

The role of radiotherapy in bone metastases: A critical review of current literature

“…The effect of concurrent administration of bisphosphonates with radiotherapy for bone metastases is documented only in nine prospective studies, all of them published after the year 2000 (Atahan et al., ; Choudhury et al., ; Gierloff et al., ; Kouloulias, Kouvaris, et al., ; Kouloulias, Matsopoulos, et al., ; Kouloulias et al., ; Mañas et al., ; Vassiliou et al., ; Zaghloul et al., ; Table ). Three prospective studies were published dealing with the administration of bisphosphonates (pamidronate and ibandronate) and EBRT alongside.…”

“…The results of the study pointed out a significant decrease in incidence of SREs, while prolonged the time of onset of SRE. A subsequent randomised controlled study compared zoledronic acid with ibandronate and pamidronate combined with radiotherapy (Choudhury et al., ). The authors reported similar results between the three arms regarding pain response and duration of pain relief.…”

“…Radiotherapy combined with bisphosphonates is safe and might improve the clinical outcome regarding pain relief while prolonging time of SREs presentation (Atahan et al., ; Choudhury et al., ; Gierloff et al., ; Kouloulias, Matsopoulos, et al., ; Mañas et al., ; Zaghloul et al., ). However due to lack of evidence, ascribed to limited number of randomised studies, it is unclear if the improvement is related to the integration of radiotherapy with bisphosphonates (Groenen et al., ).…”

An exploratory analysis of levels of evidence for articles published in Indian journal of palliative care in the years 2010-2011

“…Thus we had a final list of 90 articles for our analysis. [1112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960616263646566676869707172737475767778798081828384858687888990919293949596979899100]…”