External beam radiotherapy and radioisotope drugs

Focal external beam radiation therapy (RT) is a palliative treatment possibility that should be considered for men with CRPC and bone pain that is limited to one or a few sites. Several clinical trials as well as a systematic review of the literature suggest that single treatments with frac-tionation schedules provide palliation with cost effectiveness and patient convenience [80].

Hemibody RT could also be considered in selected patients with symptomatic disease limited to one side of the diaphragm, in order to rapid pain relief, when multiple bone metastases are present [81]. However, this technique has frequently been replaced by the administration of radioisotope pharmaceuticals which may be associated with less toxicity and are more appropriated for patients with multiple painful lesions [82]. In order for these patients to be treated with radioisotopes the presence of uptake on bone scan due to meta-static disease at sites that correlate with pain is necessary. These radioisotopes are used in men with advanced prostate cancer with osteoblastic bone metastasis. These patients are often characterized by a high ratio of bone to soft tissue metastases. Multiple radioisotopes have been used but the most extensive data are with 89-strontium (89Sr), Radium-223 and 153-samarium [153Sm). Several clinical trials provide the rational for the use of this approach in carefully selected patients [83, 84, 85].

Lexidronam (Samarium 153]. Is a complex of a radioisotope of the lanthanide element samarium with the chelator EDTMP. Particularly useful in patients with CRPC and multiple painful bone metastases, who have relapsed following initial course of hormonal or cytotox-ic chemotherapy, and in patients with progressive or recurrent symptoms at the treated sites. The goal in this stage of the disease is to maintain quality of life while managing the symptoms of the progressing cancer. Extensive data support the use of Samarium SM 153 in this group of patients [8, 9].

Alpharadin (Radium-223]. Alpharadin uses alpha radiation from radium-223 decay to kill cancer cells. Radium-223 naturally self-targets to bone metastases by virtue of its properties as a calcium-mimic. Alpha radiation has a very short range of 2-10 cells (when compared to current radiation therapy which is based on beta or gamma radiation), and therefore causes less damage to surrounding healthy tissues (particularly bone marrow). Radium-223 has a half life of 11.4 days, making it ideal for targeted cancer treatment. Furthermore, any Alpharadin that is not taken up by the bone metastases is rapidly cleared to the gut and excreted. In the phase III ALSYMPCA trial [86], Alpharadin succesfully met the primary endpoint of overall survival. When compared with placebo, Radium-223 was associated with improved overall survival (median 14.0 versus 11.2 months; HR, 0.69. A recent phase III trial envolving Alpharadin, showed a significant improvement in the median overall survival in chemo-naive patients as well as in those treated previously with docetaxel.

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