Radiotherapy commonly involves directing beams of radioactive particles at the tumour, or a radioactive source being placed within the body
Radiotherapy commonly involves directing beams of radioactive particles at the tumour, or a radioactive source being placed within the body. A radiation source can also be delivered systemically, as is the case with radium-223 chloride, being developed under the trade name Alpharadin by Algeta, in partnership with Bayer, to treat cancer patients with bone metastases.
The treatment is a source of alpha-particles that mimics the behaviour of calcium in the bone and is able to target areas of high bone turnover in and around bone metastases. Current radiotherapy based on beta or gamma particles is much more damaging to healthy cells than alpha particles, which have a range of just two to 10 cells. The radioisotope has a half-life of about 11 days, and any that is not taken up by the bone is rapidly excreted.
Several trials have been reported. In one randomised Phase II trial in 64 patients with hormone refractory prostate cancer and bone pain requiring external beam radiotherapy were given four intravenous injections of radium-223 or placebo, every four weeks.1 The median relative change in bone alkaline phosphatase concentration was a 66% decrease in those given the radionuclide, and a 9% increase in the placebo group. There was no significant difference in haematological toxic effects between the groups, and median time to prostate specific antigen progression was 26 weeks for the treatment group, and eight weeks for placebo. Two-year follow-up data indicated that 10 of the 33 treated patients and three of the 31 given placebo were still alive.2
A Phase III study has also been carried out.3 It was stopped early after an interim analysis because of the treatment’s significant efficacy, with placebo arm patients being offered Alpharadin. In the double blind, randomised, placebo controlled trial, 922 subjects with castration resistant prostate cancer and painful bone metastases were given up to six intravenous injections of the radionuclide or placebo at four-weekly intervals. The median overall survival rate for the treated group was 14 months, compared with 11 for placebo, and a median time to first skeletal-related event of 13.6 months compared with 8.4 months. There was also a 49% improvement in time to PSA progression. Bayer plans to file for approval in mid-2012.
1. S. Nilssen et al. Lancet Oncology 2007, 8, 58
S. Nilssen et al. European Cancer Conference 2009 (Berlin, 20–24 September)
3. C. Parker et al. European Multidisciplinary Cancer Congress, 2011 (Stockholm, 23–27 September)