Painful osseous metastases: analgetic effectiveness of combined application of RE-186 HEDP and SR-89 chloride: an in vivo research study

Aim: The consecutive administration of two different bone seeking radio-pharmaceuticals such as 186Re-HEDP and 89Sr-Cl was compared with 89Sr-Cl plus chemotherapy and 186Re-HEDP alone were investigated to determine the effectiveness and toxicity in pain palliation of bone metastases in patients with prostate, breast and lung cancer.Material and Methods: The effect of treatment with consecutive infusions with 186Re-HEDP and 89Sr-Cl was compared with 89Sr-Cl plus chemotherapy and 186Re-HEDP alone on pain symptoms, quality of life and bone marrow function. In total, we treated 32 patients of which 11 (Group I) were treated (5 men with prostate cancer and 6 women with breast cancer) with consecutive infusions with 186Re-HEDP and 89Sr-Cl, 12(Group II) were mostly men with prostate cancer that received 89Sr-Cl plus chemotherapy and 9 patients (Group III) 6 women with stage IV breast cancer, 1 man with lung cancer and 2 men with hepatocellular cancer with 186Re-HEDP alone. The follow up period was 16 weeks. In Group I the patients received an infusion of 186Re-HEDP [(dose of 1200MBq (32.4 mCi) ±96.21 MBq (2.6mCi)] followed by bi-weekly blood counts until 8 weeks to measure myelotoxicity. At the end of this period 89Sr-Cl was infused at a dose of 137 MBq (3.7mCi) ± 3.63MBq (0.098mCi) followed in the same manner with bi-weekly measurement in blood counts to estimate overall patient responsiveness to therapy, increase in performance and toxicity. In Group II all patients received a standard dose of 89Sr-Cl [148MBq(4 mCi) ± 2.2 MBq (0.06 mCi). In Group III all patients received a standard 186Re-HEDP dose of 1480 MBq (40 mCi) ± 3.7MBq (0.01 mCi) and Zolendronate. All patients were interviewed using standardized form of questions before and after therapy weekly for 16 weeks.Results: In Group I 91%(10/11) of the patients reported pain relief after the end of 16 weeks whereas 18% (2/11) reported discontinuation of their analgesics and remained pain-free. Pain showed a decrease from 7.8±1.7 to a value of 2.8±1.2 on a visual analogue scale (p0.2). Myelotoxicity was seen in 2/9 (22%) manifesting as grade III thrombocytopenia, 4/9 (44) as grade II and 3/9 (33%) as grade I.Conclusion: All radiopharmaceuticals used either consecutively or in combination with chemotherapy or alone were effective in metastatic bone pain palliation. There was no significant induction of Myelotoxicity except with a percentage of 33% seen in 89Sr-Cl plus chemotherapy group. In this small prospective study we achieved bone pain palliation with consecutive administration of 2 different radiopharmaceuticals. We modified slightly the dose of 186Re-HEDP such as to avoid serious and potentially lethal myelotoxicity. We achieved a greater and longer analgesic response as compared to the other two groups based on the fact that faster induction of analgesia was attained with the relatively low beta emitter 186Re-HEDP and greater pain relief with a longer duration of pain control the high beta emitter 89Sr-Cl