Taxane is new standard for HRPC, but questions remain

No prospective, randomized trials to assess the optimal timing for chemotherapy or how to approach non-metastatic, PSA-only relapse have been conducted to date, Dr. Sternberg pointed out.

"In my experience, patients who are asymptomatic are not all that eager to start chemotherapy," she told the Prostate Cancer Symposium here.

The burden of disease is an important factor when considering chemotherapy. As a general rule, Dr. Sternberg continued, chemotherapy is probably appropriate for any patient with metastatic disease.

Men who are asymptomatic with limited metastases may be good candidates for treatment, depending on patient preference and the course of the disease. Median survival is generally between 18 months and 21 months for these men.

Similarly, men who are asymptomatic with extensive metastases should receive chemotherapy, she said. Median survival for these men is about 18 months. Men who are symptomatic with metastases also should begin chemotherapy. Median survival for these patients ranges from 9 months to 16 months.

Toxicity is an issue with any type of chemotherapy, including taxanes. Weekly dosing of docetaxel may be preferable for men who experience significant side effects because each dose is lower than the once-every-3-weeks dose. Weekly dosing may also be better for older men. No statistically significant difference in results from the two regimens has been reported, but neutropenia and other side effects are generally dose related and are, therefore, less severe with the lower weekly dosing schedule.

24% reduction in death risk

The two landmark studies published in 2004-TAX 327 and SWOG 9916-showed that a docetaxel regimen can add about 2 to 2.5 months to median survival and can reduce the risk of death by 20% to 24% compared with the long-time standard of care, mitoxantrone (Novantrone) plus cortisone (N Engl J Med 2004; 351:1502-12; N Engl J Med 2004; 351:1513-20).

"Until very recently, there was no chemotherapeutic regimen shown to in-crease survival," Dr. Sternberg said. "The landscape has changed, based on these two trials. Docetaxel is now a viable alternative for our patients. Quality of life also shows improvement versus mitoxantrone."

The TAX 327 trial followed 1,006 patients to compare docetaxel plus prednisone weekly and every 3 weeks against mitoxantrone plus prednisone. The docetaxel every-3-weeks group had an overall 24% decrease in mortality versus the mitoxantrone group (p=.009). Median survival was 18.9 months in the every-3-weeks docetaxel group, 17.4 months in the weekly docetaxel group, and 16.5 months in the mitoxantrone group. The docetaxel every-3-weeks group had the most pronounced pain reduction.

The SWOG 9916 trial compared docetaxel plus estramustine to mitoxantrone plus prednisone. The docetaxel group had a 20% reduction in mortality, with median survival time of 17.5 months versus 15.6 months for the mitoxantrone group. The median time to progression with docetaxel was 6.3 months compared with 3.2 months with mitoxantrone. Half of the docetaxel group showed PSA reductions of 50% or more compared with one-quarter of patients on mitoxantrone.

"A 20% to 24% reduction in the risk of death is meaningful," Dr. Sternberg said. "This is comparable to the changes we see in other forms of cancer.