Drug combination to treat prostate cancer

Combining two new prostate cancer drugs could delay drug resistance and increase the number of men who respond to treatment suggests a new study from The Institute of Cancer Research (ICR).

Researchers at the ICR and The Royal Marsden NHS Foundation Trust have identified why men ultimately develop resistance to abiraterone – a hormone-blocking drug. Steroids and other drugs given in combination with abiraterone to control side-effects could contribute to resistance by activating mutations in the hormone-receptor gene.

However, recent trials have found that a combination of abiraterone acetate and MDV3100 can extend life for men with advanced prostate cancer. MDV3100 can block the mutation activation when combined with abiraterone.

“Abiraterone is an effective treatment for the majority of men with advanced prostate cancer, but sadly they all eventually develop resistance,” said Dr Gerhardt Attard. “Our study suggests we should combine prostate cancer drugs rather than giving the sequentially. If the results hold true in patients, this could delay drug resistance and also increase the number of men who benefit.”

The study – published in Cancer Research – also found that at high doses, abiraterone could also block the androgen receptor, like MDV3100.

“Abiraterone is normally given at 1000mg/day but it is safe at double this dose, and at this level it may have a similar ability to block resistance, so this is another promising avenue to explore,” said Professor Johann de Bono. “Around 10,000 men a year in the UK are diagnosed with advanced prostate cancer and so our findings have the potential to benefit thousands of men.”

Clinical trials are now being planned to test the combination of abiraterone and MDV3100.

Interactions of Abiraterone, Eplerenone, and Prednisolone with Wild-type and Mutant Androgen Receptor: A Rationale for Increasing Abiraterone Exposure or Combining with MDV3100