Docetaxel for Advanced Prostate Cancer

Abstract & Commentary

By William B. Ershler, MD, Editor

Synopsis: A randomized multicenter trial conducted almost a decade ago and reported in 2004 showed docetaxel plus prednisone to be superior to mitoxantrone plus prednisone for patients with hormone refractory prostate cancer. At the time of that report approximately 50% of the cohort had died. The current report examines the survival curves including the additional 310 patients who had died since the initial report. The earlier findings of superior survival for those treated with docetaxel (at 3 week intervals) and prednisone compared to mitoxantrone and prednisone stand up. Thus, this should be the preferred combination for those treated with chemotherapy off study, and the standard to which experimental approaches is be compared.

Source: Berthold DR, et al. J Clin Oncol. 2008;26:242-245.

Initial therapy for metastatic prostate cancer is typically some form of androgen ablation and this results in quite satisfactory responses in most men. However, once the disease is refractory to hormonal treatment, therapeutic success has been less readily achieved. In fact, it was just over a decade ago that the first demonstration of chemotherapy effectiveness was reported.1 In that trial, mitoxantrone plus prednisone resulted in significantly better pain relief and quality of life when compared to prednisone alone, but no survival benefit was observed. Subsequently other chemotherapy agents and combinations were examined including docetaxel, and most were compared with mitoxantrone/prednisone.

One such trial was the TAX 327 study, an international, randomized trial for which data was initially published in 2004.2 This trial compared docetaxel (75 mg/m2) administered every 3 weeks (D3), weekly docetaxel (10mg/m2) (D1), and mitoxantrone (12 mg/m2) (M), each with prednisone (5 mg orally, twice daily) (P), in 1,006 men with metastatic hormone-resistant prostate cancer. The original report was written at a time when there had been 557 deaths and the D3P treated patients had superior relief from pain, quality of life, reduction in PSA and survival, when compared to MP. The current report provides an update on the survival curves, now four years later.

Of the 1009 enrolled patients there were an additional 310 deaths that occurred in the interval bringing the total to 867 deaths. The survival benefit of D3P compared with MP has persisted with extended follow-up (P = .004). Median survival time was 19.2 months (95% CI, 17.5 to 21.3 months) in the D3P arm, 17.8 months (95% CI, 16.2 to 19.2 months) in the D1P arm, and 16.3 months (95% CI, 14.3 to 17.9 months) in the MP arm. More patients survived 3 years in the D3P and D1P arms (18.6% and 16.6%, respectively) compared with the MP arm (13.5%). Similar trends in survival between treatment arms were seen for men greater than and less than 65 years of age, for those with and without pain at baseline, and for those with baseline PSA greater than and less than the median value of 115 ng/mL.

Commentary

The present analysis confirms that survival of men with metastatic hormone refractory prostate cancer is significantly longer after treatment with the three week docetaxel prednisone regimen (D3P) than with mitoxantrone prednisone. The results are, in fact, quite similar to the original report, with consistent improvement in pain and quality of life, as well as survival. It is also apparent that weekly docetaxel plus prednisone is not quite as effective in each of these parameters as the three week schedule. The added survival of approximately 3 months (D3P vs MP) is notable but many clinicians will be equally impressed with the differences in quality of life and pain relief. In fact, it remains unclear if asymptomatic patients with hormone refractory disease are better served by immediate chemotherapy or a delay until symptoms develop. Here again, we must rely on clinical judgment, matching patient goals and weighing survival advantage vs quality of life on and off chemotherapy.

References

1. Tannock IF, et al. Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points. J Clin Oncol. 1996;14(6):1756-1764.

2. Tannock IF, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351(15):1502-1512.