TAX 327

Before TAX 327 no treatment had been shown to prolong life in hormone-refractory prostate cancer. Mitoxantrone with prednisone was the standard because it relieved pain, not because it worked.

TAX 327 randomised 1,006 men to three-weekly mitoxantrone, three-weekly docetaxel or weekly docetaxel, all with prednisone. Against mitoxantrone, three-weekly docetaxel gave a hazard ratio for death of 0.76 (95 percent confidence interval 0.62 to 0.94, p=0.009 by stratified log-rank) and weekly docetaxel 0.91 (0.75 to 1.11, p=0.36). Median survival was 16.5 months with mitoxantrone, 18.9 months with three-weekly docetaxel and 17.4 months with weekly docetaxel.

The secondary endpoints tell you what the extra months felt like. A PSA fall of at least 50 percent occurred in 32, 45 and 48 percent respectively (p<0.001 for both docetaxel comparisons). Predefined reductions in pain occurred in 22, 35 (p=0.01) and 31 percent (p=0.08), and improvements in quality of life in 13, 22 (p=0.009) and 23 percent (p=0.005). Adverse events were more common with docetaxel.

Three-weekly docetaxel with prednisone became the standard of care and stayed so for a decade, and it is still the backbone that abiraterone, enzalutamide and cabazitaxel were tested around. In England NICE TA101 recommends docetaxel for hormone-refractory metastatic prostate cancer only if the Karnofsky performance status score is 60 percent or more, with treatment stopped after up to 10 cycles, on severe adverse events or on progression, and repeat courses are not recommended if the disease recurs after a completed course.