European Multidisciplinary Cancer Congress (EMCC) 2011, 23-27 September, Stockholm

Treatment options for castration resistant prostate cancer

Dr Kurt Miller – University of Berlin, Germany


Tell me what’s really hot in the prostate cancer world because it really has heated up, has it not?

Well we had only one treatment option for castration resistant prostate cancer for the last seven or eight years and that was chemotherapy with docetaxel. The problem with that was that many people thought it’s not the appropriate treatment for asymptomatic patients and most of these patients that have hormone therapy are followed closely by the urologist and they’re getting their PSA taken regularly so most of these patients, once they get castration resistant, are asymptomatic and have a rising PSA. And most urologists are reluctant to either give them chemotherapy or refer them to the medical oncologist for chemotherapy.

And give them side effects for sure, and that 20% response rate at best.

Yes, and they also have argued that we have a three month survival advantage which is not that big and you have considerable side effects. So we’re now obviously entering a new era and we see a renaissance of hormone therapy which has been thought to be pretty dead in the last decade.

It used to be called hormone resistant, now you’re calling it castration resistant.

Yes, we changed the term to castration resistant and this is pretty much due to the advent of abiraterone that has shown that the prostate cancer cell is able to produce its own testosterone and if you stop that production you have still an effect, even if the patient has castrate levels of testosterone in his blood. So that gives the whole story a new spin and currently we have now abiraterone available in the post-docetaxel setting. Many people would think this is not the final option and there is still a trial pending over 3 or 2 showing if it’s possible to have it approved in the pre-docetaxel setting where it, and that is my belief, where it belongs. Because if you compare the side effects it has considerably less side effects than chemotherapy. But that’s not the only thing, we also have now second line chemotherapy with cabazitaxel although it also has its side effects, especially haematotoxicity; we have denosumab as an alternative to bisphosphonates.

And is there survival data yet on denosumab?

Neither with bisphosphonates nor with denosumab we have any sign or signal that it has an influence on survival. It just reduces SREs in the castration resistant setting.

But that’s still important for the man who has got skeletal related issues.

It is, definitely. Palliation it’s an important thing. But there are more in the pipeline; we have immunotherapy which is not available right now in Europe, it’s only in the US, sipuleucel-t.

That’s Provenge.

Yes, Provenge. There is still a lot of discussion looking at the price, looking at the availability and so on. So it’s still the first immunotherapy ever that has shown an overall survival advantage.

And of course there are other things in immunotherapy like ipilimumab which has broken through in melanoma.

Ipilimumab, yes, in melanoma. It’s a different type of immunotherapy though. Looking at Provenge, that is just three shots within a couple of weeks and so it has not much side effects. Ipilimumab, on the other hand, has some side effects, gastrointestinal and so on. But again we’ve never seen an advantage for any type of immune therapy for any tumour in the last thirty years for  the first time something seems to be happening.

And then there’s the alpha particle study presented here? That’s patients with bone metastasis.

Correct. This is also a kind of small paradigm shift but it’s post- and pre-docetaxel patients; it’s asymptomatic and symptomatic patients with bone metastases. And this is alpha radiation in contrast to beta radiation with strontium, uranium, alpha radiation means it’s only a short distance but it’s more effective. That’s the first time that a radionuclide has shown a survival advantage again. So this gives us totally new opportunities in terms of combinations and sequences.

So you’re optimistic?

Yes, I am. Interestingly, in all these different tumour types things do not happen in a linear fashion. It’s disruptive, sometimes nothing happens for ten years or twenty years and then, all of a sudden, everything happens at once. So I’m really optimistic that the way we treat prostate cancer in two or three years is totally different, castration resistant prostate cancer, totally different from the way we treat it in 2010 or 2011.

Kurt, thank you very much indeed. Very wise words and very helpful indeed, thank you.