General and Supportive CareRadionuclide treatment of painful bone metastases in patients with breast cancer: A systematic review
Introduction
Breast cancer is the most prevalent cancer in the world, and it is the second most diagnosed cancer with 1.15 million new cases globally in 2002.1 A large proportion of patients receive treatment with curative intent, but a notable number of patients develop metastatic disease and will eventually die from their disease. Distant metastases frequently occur to the bones and are associated with skeletal-related events. Pain is a common symptom of bone metastases and significantly affects quality of life in these patients. Treatment of the pain can be difficult. It includes common analgesics, opioid analgesics, bisphosphonates and external radiation therapy.2
Internal systemic radiotherapy with bone-seeking radioisotopes is an alternative treatment modality to external palliative radiotherapy for palliation of bone pain in osseous metastasis. Radioisotopes may be of particular importance when painful bone lesions occur in several anatomical regions or in situations where cumulative toxicity from previous radiotherapy is critical. Several radionuclides have been evaluated for pain palliation and currently three drugs have been approved by regulatory agencies and are currently marketed in Europe and the United States. This includes strontium-89 hydrochloride (Sr-89) (Megastron®, GE Healthcare) and samarium-153 lexidronam (Sm-153) (Quadramet®, Iba Molecular Imaging), which has obtained marketing approval in many European countries, the United States and other countries. Rhenium-186 hydroxyethylidenediphosphonate (Re-186) (Re-Bone®, Covidien) has been approved in some European countries.
There is evidence supporting the clinical efficacy of bone-seeking radionuclides for pain relief in bone metastasis.[3], [4], [5] The vast majority of clinical evidence arises from trials studying prostate cancer.[6], [7], [8], [9], [10] Systemic radionuclides are recommended by international cancer societies for the palliative care of bone pain in prostate cancer.[11], [12], [13]
Patients with breast cancer have participated in pivotal trials with agency-approved radionuclides, but the efficacy in breast cancer patients in particular remains unclear. The purpose of the present work was to perform a systematic review of the clinical evidence for the use of bone-seeking radionuclides managing painful bone metastasis in disseminated breast cancer.
Section snippets
Literature search strategy
The MEDLINE (Pubmed), EMBASE (Ovid) and Web of Science databases were searched for relevant articles with the terms breast cancer, bone metastasis, radionuclides, and pain in the period from 1970 to September 2009 (EMBASE from 1974). The search was customized for each database (Appendix A). Rhenium-188 was a keyword in the original search strings, but it was later revealed that this isotope has not yet gained regulatory approval. One trial with Re-188 was later withdrawn. The search retrieved
Trial overview
A total of 19 trials meet the eligibility criteria (Fig. 1; Table 1). There were three RCTs and 16 case series (uncontrolled trials). Among the 19 trials, nine trials included patients with breast cancer only (one RCT), whereas 10 mixed trials included breast cancer patients and other types of cancer patients (two RCTs). In the studies with a mixed patient population, prostate cancer was the most frequent cancer type with breast cancer patients representing 17–57% of the total study population.
Discussion
Several systematic reviews have concluded that radioisotopes provide relief of bone pain in patients with metastatic cancer.[3], [4], [23] The majority of clinical trials, including randomized comparative trials, have included patients with metastatic prostate cancer. The results of our systematic review have shown that there is limited clinical evidence of efficacy of radionuclides for relieving bone pain in metastatic breast cancer.
The systematic search included three major databases and
Role of funding source
The authors received no funding.
Conflict of interest statement
The authors declare no conflict of interest.
Acknowledgements
We thank chief librarian Hanne G. Christensen from Viborg Hospital for assistance with the literature searches.
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