Radioisotopes for metastatic bone pain

Bone metastases manifest through pain, which can arise even before the injury is radiologically detected. Pain occurs as a result of bone destruction and, as more destruction ensues, more pain can be experienced. Radiculopathies, plexopathies and shrinkage of spinal nerves due to tumour growth and fractures are very frequent in these patients. Relief of pain from bone metastasis can be achieved by treating the cancer itself; radiotherapy; conventional analgesics; and specific drugs that work on the bone tumour-induced alteration: biphosphonates, calcitonin or radioactive agents.

To determine the efficacy of radioisotopes to control metastatic pain in patients with bone metastases and complications due to bone metastases (hypercalcaemia, bone fracture and spinal cord compression) as well as its efficacy in terms of patient survival and adverse effects.

Randomised and controlled clinical trials related to this review were retrieved electronically using MEDLINE (1966-2003), EMBASE (1974-2003) and Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 1 2003). general strategies to identify RCTs were combined with specific commands to identify trials of radioisotopes and metastatic bone pain.

The inclusion criteria were: randomised trials of patients with metastatic bone pain that compared treatment with radioisotopes and placebo, and where the major outcome was either pain or complications of bone metastases (eg, hypercalcaemia, bone fracture, spinal cord compression) assessed at least four weeks after treatment.

The quality of included studies was assessed using the Jadad scale and the Oxford Pain Validity Score. Two independent reviewers extracted the data and completed a standard form designed for that purpose. An intention-to-treat analysis was performed, and global estimates of effect were calculated using a random effects model.

Four trials (325 patients) provided data that suggest a small effect of radioisotopes on pain control both at short and medium term (one to six months). No evidence was available to assess long-term effects (12 months). Only one study provided data on analgesia use and concluded that patients given either radioisotopes or placebo showed similar levels of analgesic use when compared to baseline use. Leukocytopenia and thrombocytopenia are secondary effects associated with the administration of radioisotopes. The incidence of leukocytopenia is significantly greater in patients treated with radioisotopes (RR=4.56, 95% CI (1.22,17.08)). There were also a greater number of thrombocytopenia events in the treatment group, without reaching statistical significance.

The efficacy of radioisotopes has been assessed in clinical trials with small sample sizes and short-term evaluations of the outcomes. There is some evidence indicating that radioisotopes may give complete reduction in pain over one to six months with no increase in analgesic use, but adverse effects, specifically leukocytopenia and thrombocytopenia, have also been experienced.