Strontium 89 therapy for painful bony metastases

Clinical bottom line: Strontium 89 is useful in prostatic and breast cancer. Although it may not necessarily reduce pain from existing bony metastases, it appears to decrease the number of new sites developing. Strontium 89 appears to have similar clinical response rates to other radiopharmaceuticals with selective bone localisation.

Most secondary bone lesions arise from primary carcinoma of the prostate, breast or lung, and external beam radiation therapy palliates 70% of lesions. However, this is not always adequate treatment for patients with multiple lesions and end-stage disease. In such cases pain relief is an important aspect of treatment. Radiopharmaceutical therapy can be given as an adjunct to external beam radiation for managing pain caused by skeletal metastases. Several radiopharmaceuticals, including strontium chloride 89 exist with selective bone localisation and the ability to irradiate bony metastases from within by short-range radiation.

Systematic review

Robinson RG, Preston DF, Schiefelbein M, Baxter KG. Strontium 89 therapy for the palliation of pain due to osseous metastases. JAMA. 1995; 274:420-424.

Date review completed: December 1994
Number of trials included: approximately 8 (2 randomised controlled trials)
Number of patients: approximately 1000
Control group: none, non-radioactive strontium, external beam therapy
Main outcomes: pain (analgesic requirement), clinical response rate (e.g. changes in mobility, sleep, daily activities, etc), new painful sites

Inclusion criteria were trials of intravenous strontium chloride 89 for painful osteoblastic bony metastases; outcomes included analgesic requirement, group size at least 10; three month follow-up; treatment of one injection of strontium 89; hemotoxicity data reported; English language reports.

Data on baseline and periodic pain and on baseline and periodic hemotoxicity were extracted from original reports. These data were not pooled. Response rates were defined (although not clearly) as some improvement on a relevant measure and as complete pain relief.

Findings

Included trials were mainly of patients with prostate or breast cancer. Doses of strontium 89 ranged from 0.6 MBq/kg (16 Ci/kg) to 400 MBq/kg (10.8 mCi). Only two trials were randomised controlled trials.

Randomised controlled trials

One trial compared strontium 89 with external beam therapy in 305 patients with painful prostatic metastatic cancer. Patients were assessed for suitability for local or hemibody radiation, and were then randomised to receive either radiotherapy or 200MBq (5.4 mCi) of strontium 89. Pain relief at three months was similar (no significant differences in analgesic intake), but development of painful new sites occurred in significantly fewer patients receiving strontium 89 compared with local and hemibody radiation (both p values <0.05). Significantly fewer strontium 89 patients needed radiotherapy to painful sites of pain compared with patients receiving local radiotherapy (p<0.01), but not hemibody radiotherapy.

Toxicity: There was a significantly higher incidence of adverse gastrointestinal tract effects among both groups of radiotherapy treated patients (local radiation 27%; hemibody radiation 43%) compared with strontium 89 (10%).

A second trial compared strontium 89 plus conventional radiotherapy with radiotherapy alone in 126 patients with hormone-refractory metastatic prostatic cancer (dose not stated). All patients received local field irradiation, and were then randomised to placebo or strontium 89. Overall symptom relief and survival were similar in the two groups. However strontium 89 was associated with significantly fewer new pain sites (59% versus 34%), less analgesic intake, less time to radiotherapy, fewer serum tumour markers compared with placebo, thus demonstrating a slowing of the disease process.

Toxicity: toxicity was more common in the strontium 89 group compared with placebo, with significantly higher white blood cell toxicity and platelet toxicity.

Non-controlled trials

These can be summarised as producing response rates (i.e. any change in sleep pattern, analgesic intake, work history, daily activities or mobility - as measured in trials), which varied between 50% and 90% at approximately 3-6 months. Hematologic toxicity is summarised as mild and reversible. This is similar to response rates for other radiopharmaceuticals used for cancer pain palliation. Samarium 153 ethylenediaminetetramethylenephosphonic acid (EDTMP Sm 153) has a response rte of 65% to 80% over 3.8 months, and rhenium 186 hydroxyethylenediphosphonic acid (HEDP Re 186) has a response rate of 50% to 80% over 5 weeks. Both have hematologic toxicity described as mild and reversible.

Adverse effects