Men with advanced, multi-drug resistant prostate cancer can survive a median 2·4 months longer when taking cabazitaxel. Cabazitaxel is the first drug to show a survival benefit in patients whose disease has progressed after standard chemotherapy with docetaxel, and for whom there are currently no approved treatment options. These are the conclusions of an article published in this week’si ssue of The Lancet. On the basis of these results, cabazitaxel has been given regulatory approval in the USA and is under consideration by the European Medicines Agency and other regulatory bodies.

Prostate cancer is the second most common cancer in men worldwide. For men with advanced prostate cancer, hormone therapy improves symptoms but for many patients their disease continues to progress. Docetaxel plus prednisone is the gold-standard chemotherapy treatment for these patients. But for men whose cancer becomes docetaxel resistant there is currently no treatment available that can prolong survival. However, until now, mitoxantrone was often given because of its beneficial effects on quality of life.

The new chemotherapy drug cabazitaxel has shown promising antitumour activity in patients whose cancer has progressed after docetaxel treatment.

To assess whether cabazitaxel improves overall survival compared with mitoxantrone in men with advanced multi-drug resistant prostate cancer (who had already been treated with docetaxel), an international team led by Johann de Bono, from the Royal Marsden NHS Foundation and The Institute of Cancer Research in the UK, conducted the phase 3 TROPIC trial.

755 patients were enrolled from 146 centres across 26 countries and randomly assigned to mitoxantrone (377) or cabazitaxel (378), both in combination with prednisone. The median overall survival was 15·1 months in the cabazitaxel group compared with 12·7 months in the mitoxantrone group.

The authors say: “Cabazitaxel treatment also improved median progression-free survival and time to tumour progression, and resulted in higher rates of tumour and serum prostate-specific antigen (PSA) response than did mitoxantrone.”

Adverse events were seen more often in patients taking cabazitaxel. The most common grade 3 or higher side effects found in patients in the cabazitaxel group compared with the mitoxantrone were neutropenia (82% vs 58%) and diarrhoea (6% vs <1%). Additionally, 28 patients taking cabazitaxel had febrile neutropenia compared with 5 taking mitoxantrone.

They conclude: “Cabazitaxel is the first treatment to prolong survival for metastatic multi-drug-resistant prostate cancer in the post-docetaxel setting…On the basis of these results, cabazitaxel will become a standard of care for treatment of prostate cancer in this setting.”

Commenting on the paper Tanya Dorff and David Quinn from The University of Southern California, Los Angeles, USA, said: “Cabazitaxel provides an added line of therapy for patients with castration-resistant prostate cancer…The horizon for patients with prostate cancer is promising...Therapeutic strategies in phase 3 testing include more potent suppression of androgen-receptor signalling, modulation of novel pathways in bone metastases (which afflict more than 90% of men with advanced prostate cancer), and increased anti-tumour immunity.”

 Source: The Lancet:

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)61389-X/abstract