General and Supportive Care
Radionuclide treatment of painful bone metastases in patients with breast cancer: A systematic review

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Abstract

Bone-seeking radionuclides, such as Sr-89, Sm-153, and Re-186, have been shown to have an effect on pain from bone metastasis in prostate cancer. The effect on bone pain in other cancer types, including breast cancer, remains unclear. The purpose of the study was to perform a systematic review of the use of radioisotopes for pain relief in metastatic breast cancer. A literature search was performed in PubMed, EMBASE, and Web of Science (1970 to September 2009) for clinical studies with a primary outcome of pain, performance status, or quality of life. Eligibility criteria were the following: (1) the trial must include at least 10 breast cancer patients with painful bone metastasis, (2) the radionuclide has been approved by regulatory authorities in Europe or the United States and is commercially available (Sr-89, Sm-153, and Re-186), (3) the dose of radionuclides must be clinically effective, (4) the primary endpoint must be pain, performance status or quality of life, and (5) separate reporting of efficacy should be available for breast cancer patients provided the trial included patients with various types of cancer. The literature search identified 189 individual studies of which 19 trials fulfilled the eligibility criteria. There were three randomized controlled trials of which two trials compared two different radionuclides, and one trial compared two doses of Sm-153. In addition, there were 16 uncontrolled trials. Reporting of trial research methodology in the randomized as well as the uncontrolled trials was low (median Jadad score of 1, range 1–2). Key trial details, such as patient recruitment, description of prior palliative therapies, baseline characteristics, follow up, and reporting of outcome was insufficient in a large proportion of the trials. According to Center of Evidence-based Medicine criteria, there is level 4 documentation for the effect of radionuclides in painful bone metastasis in breast cancer. It has been concluded that there is limited clinical evidence supporting the clinical effect of radionuclides in relieving pain from bone metastasis in breast cancer. Large, randomized controlled trials are needed to establish the utility of bone-seeking radionuclides in the palliative care of breast cancer patients.

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.

References (30)

  • A.T. Porter et al.

    Results of a randomized phase-III trial to evaluate the efficacy of strontium-89 adjuvant to local field external beam irradiation in the management of endocrine resistant metastatic prostate cancer

    Int J Radiat Oncol Biol Phys

    (1993)
  • D.M. Parkin et al.

    Global cancer statistics, 2002

    CA Cancer J Clin

    (2005)
  • M. Roque et al.

    Radioisotopes for metastatic bone pain

    Cochrane Database Syst Rev

    (2003)
  • G. Bauman et al.

    Radiopharmaceuticals for the palliation of painful bone metastasis-a systemic review

    Radiother Oncol

    (2005)
  • S.H. Han et al.

    The PLACORHEN study: a double-blind, placebo-controlled, randomized radionuclide study with (186)re-etidronate in hormone-resistant prostate cancer patients with painful bone metastases. Placebo controlled Rhenium study

    J Nucl Med

    (2002)
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