In metastatic prostate cancer hormone therapy works in 80% of men but eventually disease and PSA progression occur. Thereafter the options are palliation with opioids, radiotherapy to bony sites, bone seeking isotopes such as strontium, chemotherapy, androgen withdrawal response, bisphosphonates and prednisone. Mitoxantrone chemotherapy reduces pain and improves quality of life but did not improve overall survival. In this study 1006 men with metastatic hormone-refractory prostate cancer were randomized to either docetaxol plus prednisone 5 mg twice a day or mitoxantrone plus prednisone and followed for a median of 21 months. The group who received 75mg docetaxel every 3 weeks for a median of 9.5 cycles plus prednisone did better than mitoxantrone or weekly docetaxel. The 3 weekly docetaxel group had improved overall survival 18.9 months v 16.5 for mitoxantrone, a 45% rate of having the PSA halved (v 32% rate in mitoxantrone) and better reductions in pain and improvement in quality of life. The patients were median age 68, median PSA 114 and may have had either radiotherapy, surgery or hormonal therapy but no prior chemotherapy. Prior to starting the treatment, all men had to wait 4-6 weeks for the effects of antiandrogen withdrawal response on PSA to wear off. Patients had to have good performance status, a normal to high normal creatinine, no brain metastases, normal cardiac function per echocardiogram or gated scan. In the docetaxel group there were no treatment related deaths, however side effects included neutropenia, fatigue, diarrhea, alopecia and nail changes, sensory neuropathy, nausea, vomiting.