Repeated Bone-Targeted Therapy for Hormone-Refractory Prostate Carcinoma: Randomized Phase II Trial With the New, High-Energy Radiopharmaceutical Rhenium-188 Hydroxyethylidenediphosphonate

Abstract

Compared with single-injection therapy, repeated bone-targeted therapy with rhenium-188 HEDP administered to patients with advanced progressive hormone-refractory prostate carcinoma enhanced pain palliation and improved progression-free and overall survival. Larger studies are justified to further evaluate the use of rhenium-188 HEDP.

Palliation and Survival After Repeated 188Re-HEDP Therapy of Hormone-Refractory Bone Metastases of Prostate Cancer: A Retrospective Analysis

“…In addition, 39% of patients with repeated treatments exhibited a decrease in prostate-specific antigen levels of more than 50% for at least 8 wk. These results were interpreted to indicate that repeated 188 Re-HEDP therapy is beneficial in patients with prostate cancer and bone metastases (18).…”

“…Uptake in the skeleton is between 20% and 30% of the injected dose for 186 Re-HEDP and between 30% and 50% for 153 Sm-EDTMP. Accumulation in metastatic lesions is between 3 and 20 times as high as in normal bone, and the effective half-lives of 188 Re-HEDP and 153 Sm-EDTMP are between 2 and 3 d. 188 Re-HEDP has been used for pain palliation in patients with prostate cancer and bone metastases since the early 1990s (15,16 (18) designed to compare the efficacy of multiple successive injections with that of a single administration of this agent. The effectiveness of 188 Re-HEDP for pain palliation was better in the repeated-treatment group, with a response rate and time of response of 92% and 5.66 mo, respectively.…”

Bone Seeking Radiopharmaceuticals for Metastatic Bone Pain

“…This was confirmed in a randomized controlled trial in prostate cancer patients treated with two dosages of 1.1 mCi 188 Re-HEDP with an interval of eight weeks compared to single shot treatment. They did not only find an improved pain response with longer duration but surprisingly an improved survival as well (Palmedo et al 2003). Safety of repeated treatment with bone seeking radiopharmaceuticals was also confirmed (Sartor et al 2007).…”

“…In theory, this high dose rate could lead to improved efficacy with rapid recovery. This is ideal for combined treatment regimens and for repeated treatment, which has already shown to be favourable with regard to pain response and survival (Palmedo et al 2003). Several other combinations using bone seeking radiopharmaceuticals are under investigation.…”

A paradigm for the treatment of prostate cancer bone metastases based on an understanding of tumor cell–microenvironment interactions

“…Radioisotopes are effective therapeutic agents for the management and palliation of bone-specific disease due to the high levels of retention by bone metastases (highest in damaged bone, less in normal bone tissue, and no retention outside of bone). The most common radioisotopes are strontium-89 and samarium-135 lexidronam ethylene diamine tetramethylene phosphonate [Graham et al, 1999;Dafermou et al, 2001;Palmedo et al, 2003]. These radionuclides are betaemitting radioisotopes that differ primarily in their radioactive half-lives and the tissue penetrance of their beta particles.…”