Alpha results for new cancer radiotherapy

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Alpha results for new cancer radiotherapy

By Mike Nagle

02/03/2007- An anti cancer therapy that emits the most lethal from of radiation has successfully made it through second stage human trials.

Norway-based pharma, Algeta has developed a drug using a high-energy, relatively short-lived isotope of radium (223), which emits alpha-particle radiation. Alpharadin is being investigated as a means of killing prostate cancer cells that have spread to nearby bones and has recently successfully completed a Phase II trial. The results show that the therapy could extend survival by around six months.

An estimated 1.5 million patients worldwide suffer from cancer that has spread to bones with approximately 300,000 new cases per year. Prostate and breast cancers account for more than 80 per cent of all these cases. Using current treatments, patients only survive an average of three years.

Algeta hopes Alpharadin will improve this situation because alpha radiation is the most deadly form of radiation and so can kill cancer cells more quickly than radioactive compounds that emit beta-radiation - the majority of current radiopharmaceuticals rely on beta-emitting particles.

In the trial of 65 patients, patients treated with Alpharadin survived, on average, up to 25 weeks (53 per cent) longer than the 46.4 weeks that patients receiving placebo survivied. 18 months after the trial, 15 patients in the Alpharadin group were still alive compared to 6 in the control group.

In the trial, Alpharadin also resulted in reduced levels of prostate-specific antigen (PSA), a widely used biomarker for the diagnosis of prostate cancer. PSA levels were found to be lowered for up to three months after treatment finished.

Algeta's CEO, Dr Thomas Ramdahl told DrugResearcher.com that Alpharadin is the most advanced alpha-emitter in development with the majority of other research in the area coming out of academic groups.

Dr Ramdahl explained that the therapy has several potential advantages over current radiotherapy. Beta-radiation travels a lot further through the body, and therefore it can be absorbed in areas not affected by the target cancer, for example, killing bone marrow.

Alpharadin, on the other hand, "does not penetrate bone marrow. It has very little uptake in other tissues," according to Dr Ramdahl. This can reduce possible side-effects of the therapy; alpha-emitters only travel two to 10 cell lengths before they are absorbed.

He added that the therapy is self-targeting. The molecule can take advantage of the fact that it has similar chemical properties to calcium and be rapidly recruited to bones.

There are around 100 radionucleotides that emit alpha radiation. Only a few are considered useful as therapeutics, including thorium-227, astatine-211, bismuth-213 and actinium-225.

Radium was first discovered by Marie Curie over 100 years ago and has been used as a cancer therapy in the past. However, the heavier isotope that was used (Ra-226) has a half-life of over 1,600 years and so was deemed too dangerous for medical use. By comparison, Ra-223 loses half its potency in around 11 and a half days and so side-effects from treatment should also be more short lived.

However, the very short half-life could also limit the drug's use; the therapy must get to the right place in the body quickly before it begins to lose its effectiveness.

This specific isotope also has logistical advantages, according to Dr Ramdahl.

He said: "[it] can be used in commercial quantities and has a half-life suitable for shipping. Radium-223 is also very high energy and so the dose needed is low, which makes shipping and handling easier."

Ageta also develop drug delivery techniques to improve specificity. As Dr Ramdahl said: "With alpha-emitters, precise targeting is the key."

He explained that the company work on three different technologies based on microparticles, radionucleotide labelled antibodies and liposomes loaded with the drugs "as targeting vehicles." Of these programmes, Dr Ramdahl said that the first two are the most advanced and the company is also using these techniques to develop therapies that use thorium.

Apharadin is also currently in two other Phase II trials to treat prostate cancer. However, he company believes that the drug could also be used to treat other cancers that spread to bones - for example, breast, lung, kidney and thyroid.

Dr Ramdahl said: "Alpharadin is demonstrating that it has a valuable clinical effect by increasing the survival of the most seriously ill patients, while also showing signs that it can alleviate the associated pain, thereby improving quality of life."

He continued: "Based on the positive results we have seen in clinical trials to date, we have initiated preparations for pivotal Phase III clinical trials with Alpharadin as we progress this novel anticancer therapy towards the market."

Researchers at Oak Ridge National Laboratory are examining the use of antibodies to carry bismuth-213 to blood vessels in the lung to treat cancer. Clinical trials of the therapy are currently being conducted at the Memorial Sloan-Kettering Cancer Center and a number of other US locations.

Scientists at Gothenburg University are evaluating astatine-211 as a potential therapy for ovarian cancer.

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