Thrombocytopenia is the most important dose-limiting toxicity of radiopharmaceutical therapy.12 Recently, a phase I study was conducted to investigate the toxicity of rhenium-186 hydroxyethylidene diphosphonate (Re-186), a radionuclide approved for use in Europe, when it is used in combination with docetaxel in men with castration-resistant prostate cancer.10,12 Six cycles of docetaxel 75mg/m2 were administered, and Re-186 was given at a fixed dosage of 1250MBq or 2500MBq.12 Grade 1, grade 2, and grade 3 thrombocytopenia was recorded during 16%, 4%, and 2% of cycles of therapy, respectively, and there were no occurrences of grade 4 thrombocytopenia. One occurrence of grade 3 thrombocytopenia, which lasted >10 days, was considered dose-limiting. Further studies are planned to determine whether combining docetaxel and Re-186 improves survival.
An Alternative to Bisphosphonates?
Bisphosphonates are considered the standard of care for treatment of painful osteoclastic and osteoblastic lesions in patients with bone metastases, but they must be given intravenously, may require renal monitoring during their use, and may have potential to cause osteonecrosis of the jaw.13 Denosumab is a human monoclonal antibody against the osteoclast stimulator RANKL that has been shown to reduce osteoclastic bone destruction, and is given subcutaneously.14 In a recent trial, denosumab and zoledronic acid were compared for prevention of SREs in 1,904 men with castration-resistant prostate cancer.14 Patients were randomized to either 120mg denosumab or 4mg zoledronic acid every 4 weeks and examined for SREs every 12 weeks. The time to the first SRE was delayed by 3.6 months in the denosumab group (20.7 months vs. 17.1 months; HR 0.82, 95% CI 0.71-0.95, P=0.008). Overall survival and disease progression did not differ between groups. Adverse events occurred at similar rates in the two groups, although patients taking denosumab had a higher incidence of hypocalcemia. Osteonecrosis of the jaw occurred in 1% of the zoledronic acid group and 2% of the denosumab group.
CIBP remains a challenging complication in many types of cancer, and often patients require multiple treatment approaches to achieve pain relief. Recent research in radiation therapy, radionuclide therapy, and bone-modifying therapy has identified potential new options for treatment of CIBP that may soon offer safer, more effective pain control.
1. Middlemiss T, Laird BJ, Fallon MT. Mechanisms of cancer-induced bone pain. Clin Oncol (R Coll Radiol). 2011;23(6):387-392.
2. Grossman SA, Nesbit S. Cancer pain. In: Abeloff MD, Armitage JO, Niederhuber JE, Kastan MB, McKenna WG, eds. Abeloff’s Clinical Oncology. 4th ed. Philadelphia, PA: Churchill Livingstone Elsevier; 2008.
3. Wee B, Hillier R. Pain control. Medicine. 2011;39:639-644.
4. Colvin L, Fallon M. Challenges in cancer pain management—bone pain. Eur J Cancer. 2008;44(8):1083-1090.