Alpha Emitters Hit the Clinic

Michael Spiotto, MD, PhD

Michael Spiotto, MD, PhD

By Michael Spiotto, MD, PhD

It has taken almost 100 years for radium to come into vogue again. After its discovery by Marie Curie in 1898, radium quickly gained notoriety as a curative panacea, incorporated into toothpaste, water purifiers and day spas.

In one classic example, “Radium Girls” used this isotope to paint glow-in-the-dark watch dials, ingesting the radium-laced paint by licking their brushes to create a finer point.

However, this use quickly made the element  infamous in the public eye by the anemia and bone cancers subsequently suffered by these women.

The type of radium typically used at the time, radium-226, has a half-life of 1,601 years. Its volatility in vaporizing to a gaseous state (poisonous radon gas) makes it difficult to contain, store, administer and dispose of – rendering it unsuitable for medical applications.

However, radium-226’s cousin, radium-223, is emerging as an attractive candidate for medical use given its shorter half-life of 11 days and easier use of storage.

In fact, we were the first academic medical center to use it earlier this summer for prostate cancer. Read more about that here.

In last month’s New England Journal of Medicine, Chris Parker, MD, of the Institute for Cancer Research in the U.K., and his collaborators,  presented novel findings that intravenous radium-223 (Alpharadin) improved survival in metastatic prostate cancer patients with bone metastasis 1, 2.

We call these unsealed radioactive sources as they are soluble isotopes that deliver systemic radiation.

While these sources have different uses depending on their properties, Radium-223 is actively incorporated during bone remodeling that occurs in metastasis.

What is novel is that radium-223 emits alpha particles that are more biologically effective than current unsealed sources that emit beta particles or gamma rays.

Unlike other unsealed sources, these alpha particles travel only a tenth to a hundredth of the distance of other particles and, therefore, are more likely to kill the adjacent cancer cells and not the normal bone marrow.

Parker et al. provides the first evidence that radium-223 improved survival: 14.9 months for radium-223 treatment vs. 11.3 months for placebo.

In addition to improved survival, radium-223 delayed time to first symptomatic metastasis to the bones by almost six months as well as other improved outcome metrics.

Plus, this treatment was associated with very low bone marrow toxicity. Thus, radium-223 may become a mainstay of treatment.

Radium-223 provided just as good if not better outcomes compared to other bone-seeking radioisotopes, radiation therapy or chemotherapy.

In contrast to radium-223, other radiopharmaceuticals to treat bone metastasis, such as Samarium-153 (Quadramet) 3 or Strontium-89 (Metastron) 4, showed no difference in overall survival or decreased pain, and may have increased hematologic toxicities.

Furthermore, radium-223  had similar improved survival as other chemotherapeutics 5, 6 and immunotherapies 7.

In summary, radium-223 may quickly become a standard of care in the clinic for people with cancer metastatic to the bone.

One bottleneck to its implementation may be the equipment necessary to safely store and to monitor this radioactive agent.

Still, this treatment may extend beyond patients with prostate cancer as breast cancer, lung cancer and other types of cancer frequently metastasize to the bone. Further study is warranted but radium-223 is likely to make an impact in the future.

Michael Spiotto, MD, PhD, is an Assistant Professor of Radiation & Cellular Oncology at the University of Chicago Medicine. He specializes in treating patients with head and neck cancer. Whenever possible, he uses image-guided radiation therapy to target a tumor more precisely while reducing damage to surrounding tissue.

References

1.     Parker C, Nilsson S, Heinrich D, Helle SI, O’Sullivan JM, Fossa SD, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. Jul 18;369(3):213-223.

2.     Vapiwala N, Glatstein E. Fighting prostate cancer with radium-223–not your Madame’s isotope. N Engl J Med. Jul 18;369(3):276-278.

3.     Serafini AN, Houston SJ, Resche I, Quick DP, Grund FM, Ell PJ, et al. Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind placebo-controlled clinical trial. J Clin Oncol. Apr 1998;16(4):1574-1581.

4.     Porter AT, McEwan AJ, Powe JE, Reid R, McGowan DG, Lukka H, et al. Results of a randomized phase-III trial to evaluate the efficacy of strontium-89 adjuvant to local field external beam irradiation in the management of endocrine resistant metastatic prostate cancer. Int J Radiat Oncol Biol Phys. Apr 2 1993;25(5):805-813.

5.     de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. Oct 2;376(9747):1147-1154.

6.     de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. May 26;364(21):1995-2005.

7.     Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. Jul 29;363(5):411-422.

 

%d bloggers like this: