The PLACORHEN study: a double-blind, placebo-controlled, randomized radionuclide study with (186)Re-etidronate in hormone-resistant prostate cancer patients with painful bone metastases. Placebo Controlled Rhenium Study.
(186)Re-1,1-hydroxyethylidene diphosphonate (etidronate) can be used for the palliative treatment of metastatic bone pain. A randomized, placebo-controlled study using (186)Re-etidronate was conducted on end-stage prostate cancer patients with metastatic bone pain.


METHODS
Pain relief was assessed using an electronic diary containing questions reflecting the multidimensional character of chronic pain. The diary was marked twice daily for a maximum of 14 wk (2 wk before and 12 wk after the injection). Pain response was determined using a specific decision rule in which pain intensity, medication index, and daily activities were the core determinants. A positive response day was defined as a day on which pain intensity was reduced > or = 25% compared with baseline values, while medication index and daily activities were at least constant, or on which pain intensity was reduced < 25% and medication index or daily activities improved > or = 25%, without worsening of the remaining factor. The total response (%) was defined as the number of positive response days divided by the number of days of follow-up.


RESULTS
Of the 111 included patients, 79 were evaluable (43 (186)Re-etidronate, 36 placebo). Thirty-two patients were excluded from the analysis because of incomplete datasets. The total response of the patients treated with (186)Re-etidronate varied from 0% to 96% (mean, 27%, or 23/84 d). In the placebo group, the total response varied from 0% to 80% (mean, 13%, or 11/84 d; Mann-Whitney U test, P < 0.05). The number of patients who requested radiotherapy was higher in the placebo group (67%) than in the (186)Re-etidronate group (44%) (relative risk, 1.51; Fisher's exact test, P = 0.069).


CONCLUSIONS
This randomized controlled trial confirmed that, compared with placebo, (186)Re-etidronate resulted in a significantly longer pain response in the treatment of bone pain from metastasized prostate cancer.
Han
Shiuw H
SH
Department of Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands. shiuw.han@planet.nl
de Klerk
John M H
JM
Tan
Suzy
S
van het Schip
Alfred D
AD
Derksen
Bert H
BH
van Dijk
Aalt
A
Kruitwagen
Cas L J J
CL
Blijham
Geert H
GH
van Rijk
Peter P
PP
Zonnenberg
Bernard A
BA
D000368:Aged; D001859:Bone Neoplasms / Q000532:radiotherapy* / Q000556:secondary*; D004311:Double-Blind Method; D012968:Etidronic Acid / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009942:Organometallic Compounds / Q000627:therapeutic use*; D010147:Pain Measurement; D010166:Palliative Care; D011471:Prostatic Neoplasms / Q000473:pathology*; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D012211:Rhenium / Q000627:therapeutic use*; D014004:Tin Radioisotopes / Q000627:therapeutic use*
D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D014004:Tin Radioisotopes; C064573:rhenium-186(tin)etidronate; D012211:Rhenium; D012968:Etidronic Acid