Strontium and calcium are both in Family 2 of the Periodic Table, with the former atom slightly larger than the latter. The body does not distinguish between these two elements with the result that Sr-89 is distributed throughout bone as it can substitute for calcium in hydroxyapatite. First suggested for therapeutic efficacy in the 1940s, Sr-89 came into wider use after the successful alleviation of bone pain by several German groups of investigators who reported response rates of up to 90%, using dosages from 1 to 3 mCi. A number of dose escalation studies have indicated that 40 to 60 uCi/kg body weight produce response rates which do not increase with higher dosages, although more toxicity is seen at higher administered activities with this, and all other, radiopharmaceuticals used for this purpose. Response rates have been reported from 40% to 90%, depending on the criteria used. Some, but not all, investigators have found a better response to Sr-89 in patients with higher performance scores. For example, in a study of patients with a mean survival of 23 weeks, only 29% experienced any pain relief.
Pain palliation response duration from Sr-89 has ranged between 6 and 12 weeks. A review of 18 articles describing treatment of 715 patients with dosages of Sr-89 from 1 to 12 mCi yielded response rates of 65%. Most investigators do not see a clear dose-response rate with this, or the other radiotracers under discussion employing further dose escalation once a threshold for pain relief has been reached. Most of these studies were performed on patients with metastatic prostate carcinoma, but equivalent effects have been reported for metastases from breast and other carcinomas. When a drop in prostate specific antigen (PSA) levels has been used as a marker of cytotoxicity, there seems to be no correlation between this phenomenon and pain relief.
Several placebo-controlled studies have been performed employing Sr-89, with response rates ranging between 59% and 67% in the treated groups and 21% and 34% in the placebo groups. In a study comparing Sr-89, teletherapy, and hemibody radiation the response rates were similar, ranging from 61% to 66%. Platelet and leukocyte counts of the Sr-89-treated patients showed decrements of 30-50% without clinical sequelae. On follow-up, the Sr-89-treated group had fewer new sites of metastatic disease than the other two groups.
As an adjuvant to teletherapy given for a solitary painful site, Sr-89, given at a rather high dosage of 10.8 mCi delayed the need for further radiotherapy to the previously treated site and also the appearance of pain at new sites when compared with the patients who received teletherapy with placebo. This has also been demonstrated with a dosage of 5.4 mCi, closer to the usual dosage of 4 mCi employed in the United States. As a result, less pain medication and a higher quality of life were recorded for the patients receiving teletherapy plus adjuvant Sr-89, although there was no difference shown in survival. Only grade 1 myelotoxicity was seen with Sr-89 in this study.
Only Sr-89 has been shown to delay the time until recurrent or new sites of pain requiring teletherapy appear. This effect has not been sought, or at least published, in research on the other radiopharmaceuticals in the table. The success of Sr-89 in providing this benefit probably relates to the long effective half-life of the radiopharmaceutical in bone.
In a retrospective study of patients with progressive bone pain, spinal cord compression was completely prevented in those receiving palliative teletherapy, and occurred in only 4% of those receiving Sr-89, but in 21% of the patients treated with a nitrogen-containing bisphosphonate, olpadronate, and in 50% of historical controls. This research needs to be repeated in a prospective study because of its important implications for patient care.
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