Pain palliation therapy of bone metastases: palliative or curative?

In Germany the incidence of breast cancer is about 85 and of prostate cancer about 50 new patients per 100.000 inhabitants/year. In about 80% of prostate cancer patients and 75% of breast cancer patients bone metastases are observed in autopsy. Most of these patients develop severe pain syndrome from bone metastases reducing quality of life during life time. Therapy of these patients should aim at adding life to the years not years to their life. The knowledge of metastatic cell biology, of cell-cell interaction and of tumor-cell, tumor cell-skeleton interaction may modify the therapeutic procedure. Already in 1940/41, Pecher treated a patient suffering from painful prostate cancer bone metastases administering 296 MBq 89Strontium chloride. About 10 years later, Friedell introduced 32Phosphorus for treatment of bone metastases from breast cancer. Today in Europe 3 radionuclides are approved for pain palliation therapy as shown in Table.1. Indication: - pain palliation therapy of bone metastases from prostate cancer (89Sr and 186Re); - pain palliation of all osteoblastic metastases independent from primary tumors (153Sm). Contraindications: - pregnant and lactating females - myelosuppression (<2.400/mm3 granulocytes; <60.000/mm3 platelets); - impaired renal function (urea >12 mmol/l; creatinine > 150 mmol/l) - incontinence; - acute or chronic spinal cord compression and/or brain metastases causing neurological symptoms; - disseminated intravascular coagulopathy. The recommended activities per treatment are: 89Sr 150 MBq, 186Re 1.295 MBq, and 153Sm 37 MBq/kg BW. Shortly (6-8 weeks) prior to radionuclide therapy for pain palliation no high dose chemotherapy or large field radiation therapy should be performed. Stopping unlabelled bisphosphonate therapy prior to pain palliation therapy is not necessary. This radionuclide therapy may be repeated several time, the interval between tracer administration depends on blood cell count rate. The recommended intervals are for 89Sr about 6 months, for 153Sm and 186Re 6-10 weeks. A response rate of about 70-80% is reported, the onset can be expected after 7-day after administration of 153Sm and 186Re, after 2 weeks using 89Sr. This radionuclide therapy can be performed on outpatient basis, depending on national regulations. Radionuclide therapy alone is no curative treatment of bone metastases, but combination therapy with chemo- and/or radiation therapy have shown strong synergistic effect, improving the response on pain syndrome and disease control as well as prolonging mean survival as shown in several clinical trials