<sup>188</sup> Re Zoledronic Acid in the Palliative Treatment of Painful Bone Metastases

Authors

  • Tatiana Kochetova ational Medical Radiological Research Center” of the Ministry of Health of the Russian Federation, Korolev str. 4, Obninsk, Kaluga region, Russia
  • Valeriy Krylov ational Medical Radiological Research Center” of the Ministry of Health of the Russian Federation, Korolev str. 4, Obninsk, Kaluga region, Russia
  • Maxim Smolyarchuk ational Medical Radiological Research Center” of the Ministry of Health of the Russian Federation, Korolev str. 4, Obninsk, Kaluga region, Russia
  • Dmitriy Sokov Clinical Oncology Dispensary No1, Baumanskaya str. 17/1, Moscow, Russia
  • Alexander Lunev Federal Medical Biophysical Center of FMBA, Russia, Zhivopisnaya str. 46, Moscow, Russia
  • Sergey Shiryaev N.N. Blokhin Russian Cancer Research Center” of the Ministry of Health of the Russian Federation, Kashirskoe shosse, 24, Moscow, Russia
  • Olga Kruglova National Medical Radiological Research Center” of the Ministry of Health of the Russian Federation, Korolev str. 4, Obninsk, Kaluga region, Russia
  • Tatiana Makeenkova Obninsk Institute for Nuclear Power Engineering, Studgorodok 1, Obninsk, Kaluga region, Russia
  • Karina Petrosyan National Medical Radiological Research Center” of the Ministry of Health of the Russian Federation, Korolev str. 4, Obninsk, Kaluga region, Russia
  • Alexandra Dolgova Obninsk Institute for Nuclear Power Engineering, Studgorodok 1, Obninsk, Kaluga region, Russia
  • Marina Poluektova National Medical Radiological Research Center” of the Ministry of Health of the Russian Federation, Korolev str. 4, Obninsk, Kaluga region, Russia
  • Vsevolod Galkin National Medical Radiological Research Center” of the Ministry of Health of the Russian Federation, Korolev str. 4, Obninsk, Kaluga region, Russia
  • Andrey Kaprin National Medical Radiological Research Center” of the Ministry of Health of the Russian Federation, Korolev str. 4, Obninsk, Kaluga region, Russia

Keywords:

Bone metastases, 188Re-Zoledronic acid, Radiopharmacy, 153Sm-EDTMP, 89SrCl2

Abstract

188Re Zoledronic acid (188Re-ZA) is new radiopharmaceutical which may have advantages over other bone seeking β-emitters due to high radiation energy of 188Re, and metabolic effect of zoledronic acid.

In the phase I-II of the study therapeutic dosage of 188Re-ZA was estimated. Pharmacokinetics, dosimetry and safety were assessed in the dose escalation study. Twenty-one (3, 3 and 15) breast and prostate cancer patients with multiple painful bone metastases received 35, 45 and 55 MBq of 188Re-ZA respectively. In the next step 42 new patients were randomized in 2 groups (188Re-ZA in dosage of 45 MBq/kg and 89SrCl2 in dosage of 150 MBq) to assess safety and efficacy of the radiopharmaceuticals, the follow up lasted for 9 weeks.

Absorbed dose to the bone marrow is respectively low 0.26±0.06 Gy. The dose escalation study shows that 188Re-ZA the dosage of 55 MBq/kg is safe, no significant hematologic or any other toxicity is observed. 89SrCl2 in a dosage of 150 MBq, as compared to 188Re-ZA in a dosage of 45 MBq/kg demonstrates similar efficacy, but the effect starts faster in 188Re-ZA group. By the end of the follow up some patients demonstrated pain recurrence, this may indicate the need for repeated courses of treatment. Though many patients with widespread bone metastases and the higher base level of alkaline phosphatase were in the 188Re-ZA group, in the majority of cases of both groups stabilization of the disease was achieved and continued for at least two months. Both radiopharmaceuticals demonstrated acceptable safety profile. Although trend in reduction of hemoglobin level was observed, especially in the group of patients with baseline anemia, both radiopharmaceuticals significantly impact on the platelet counts (PLT) only. As it was predicted by dosimetry data, 188Re-ZA in a dose of 45 MBq/kg is safer, by the week 6 the PLT counts in the 188Re-ZA group became almost the same as baseline and even higher in the week 9, while in the 89SrCl2 group in the week 9 PLT counts remained below the baseline; the difference was statistically proven. It seems that patients with breast cancer, in contrast to those with prostate cancer, have benefit (not statistically significant) in overall survival: 20.7 vs 15.6 months regardless dosage or type of radiopharmaceutical.

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Published

2017-07-31