What is the toxicity of unsealed radioisotopes for treatment of metastatic prostate cancer?

As these radioisotopes are taken up by bone, they have the potential to suppress the bone marrow and result in low red and white blood cell and platelet counts which can then lead to dependence on blood transfusions, increased risk of infections and easy bruising. Patients who have low blood counts at the outset would generally be regarded as being unsuitable and ineligible for this treatment.

All the strontium 89 and samarium 153 trials reported toxicity outcomes.

Thrombocytopenia and/or leucopenia were observed to some extent in all studies. strontium 89 tends to show a similar or worse effect on thrombocytopenia and leucopenia than hemibody and local irradiation^[1]^[2], more effect than ‘best supportive care’ ^[3]^[4], and statistically significantly more effect when added to localised radiation.^[5]^[6] There is no good evidence that strontium 89 causes significant adverse effects other than haematological. All the samarium trials demonstrate a reduction in platelets and white cell count with samarium 153. In one trial this effect is statistically significant for white blood cell toxicity.^[7] However, the development of grade III or IV neutropaenia is uncommon (<15%). There are no data on increased risk for fractures.

An association of radioisotope therapy with life-threatening haematological toxicity would be of high clinical impact, particularly when other treatment options for palliation are available. The small numbers in these studies mean that they are unlikely to be sufficiently powered to exclude a meaningful increase in fatal adverse events associated with the use of radioisotopes.

Furthermore, currently patients in Australia considered for radioisotope treatment are likely to bemore heavily pre-treated with chemotherapy than those entered into these studies. The haematological toxicity is possibly much more marked in these pre-treated patients, thus great care must be made extrapolating these results to prostate cancer patients who have been pre-treated with chemotherapy or who have significant marrow infiltration prior to starting radiotherapy.

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Evidence summary and recommendations

Evidence summary

Level

References

Men with hormone refractory prostate cancer and painful bone metastases

strontium 89

At the doses administered, and in a population of patients who were not pre-treated with chemotherapy, strontium 89 appears associated with mild haematological toxicity. The possibility of significant serious adverse events cannot be excluded by the published trials, compared with the use of best supportive care or localised radiation.

II

^[3], ^[4], ^[1], ^[2], ^[5], ^[6], ^[8]

samarium 153

The limited evidence demonstrates that samarium 153 results in falls in white cell counts and platelets. However, in patients with adequate marrow reserve, the development of grade III or IV neutropaenia or thrombocytopaenia is uncommon (<15%) and clinically significant toxicity is rare. There is no randomised evidence comparing samarium with other radioisotopes such as strontium.

II

^[7], ^[9], ^[10], ^[11]

Evidence-based recommendation

Grade

Unsealed radioisotopes alone may be associated with higher haematological adverse

events compared with supportive care or localised radiation, although overall these rates are low. Unsealed radioisotopes in combination with other treatments such as radiotherapy have higher rates of serious toxicity than radiotherapy alone. The toxicity of unsealed radioisotopes in combination with modern chemotherapy (taxanes) has not yet been defined and caution should be exercised if such combinations are considered.

C

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