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, more effect than ‘best supportive care’ , and statistically significantly more effect when added to localised radiation. 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. 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.
Evidence summary and recommendations
| Men with hormone refractory prostate cancer and painful bone metastases
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||, , , , , , |
| 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||, , , |
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.
- Quilty PM, Kirk D, Bolger JJ, Dearnaley DP, Lewington VJ, Mason MD, et al. A comparison of the palliative effects of strontium-89 and external beam radiotherapy in metastatic prostate cancer. Radiother Oncol 1994 Apr;31(1):33-40 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/7518932.
- Oosterhof GO, Roberts JT, de Reijke TM, Engelholm SA, Horenblas S, von der Maase H, et al. Strontium(89) chloride versus palliative local field radiotherapy in patients with hormonal escaped prostate cancer: a phase III study of the European Organisation for Research and Treatment of Cancer, Genitourinary Group. Eur Urol 2003 Nov;44(5):519-26 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/14572748.
- Buchali K, Correns HJ, Schuerer M, Schnorr D, Lips H, Sydow K. Results of a double blind study of 89-strontium therapy of skeletal metastases of prostatic carcinoma. Eur J Nucl Med 1988;14(7-8):349-51 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/2460352.
- Lewington VJ, McEwan AJ, Ackery DM, Bayly RJ, Keeling DH, Macleod PM, et al. A prospective, randomised double-blind crossover study to examine the efficacy of strontium-89 in pain palliation in patients with advanced prostate cancer metastatic to bone. Eur J Cancer 1991;27(8):954-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/1716935.
- Porter AT, McEwan AJ. Strontium-89 as an adjuvant to external beam radiation improves pain relief and delays disease progression in advanced prostate cancer: results of a randomized controlled trial. Semin Oncol 1993 Jun;20(3 Suppl 2):38-43 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/7684865.
- Porter AT, McEwan AJ, Powe JE, Reid R, McGowan DG, Lukka H, 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 Apr 2;25(5):805-13 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8478230.
- Serafini AN, Houston SJ, Resche I, Quick DP, Grund FM, Ell PJ, et al. Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind placebo-controlled clinical trial. J Clin Oncol 1998 Apr;16(4):1574-81 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/9552068.
- Smeland S, Erikstein B, Aas M, Skovlund E, Hess SL, Fosså SD. Role of strontium-89 as adjuvant to palliative external beam radiotherapy is questionable: results of a double-blind randomized study. Int J Radiat Oncol Biol Phys 2003 Aug 1;56(5):1397-404 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12873686.
- Sartor O, Reid RH, Hoskin PJ, Quick DP, Ell PJ, et al. Samarium-153-Lexidronam complex for treatment of painful bone metastases in hormone-refractory prostate cancer. Urology 2004 May;63(5):940-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15134985.
- Resche I, Chatal JF, Pecking A, Ell P, Duchesne G, Rubens R, et al. A dose-controlled study of 153Sm-ethylenediaminetetramethylenephosphonate (EDTMP) in the treatment of patients with painful bone metastases. Eur J Cancer 1997 Sep;33(10):1583-91 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/9389919.
- Tian JH, Zhang JM, Hou QT, Oyang QH, Wang JM, Luan ZS, et al. Multicentre trial on the efficacy and toxicity of single-dose samarium-153-ethylene diamine tetramethylene phosphonate as a palliative treatment for painful skeletal metastases in China. Eur J Nucl Med 1999 Jan;26(1):2-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/9933654.