Docetaxel clears more hurdles in phase II prostate cancer trials

Data from two separate phase II studies show docetaxel (Taxotere) to be an increasingly promising therapy in the more advanced and aggressive forms of prostate cancer.One study of the agent in prostatectomy patients at high risk of recurrence showed that the drug, administered intravenously, was well tolerated with only two (2.6%) of the 77 patients in the trial experiencing grade IV toxicity (hyperglycemia).

"The goal now is to see if earlier treatment can provide a more robust survival advantage. Our next job is to demonstrate a survival advantage for adjuvant treatment," co-author Adam Kibel, associate professor of urology at Washington University Medical Center, St. Louis, told Urology Times.

Data from a phase II trial of docetaxel and thalidomide versus docetaxel alone published earlier this year suggested a trend toward an increase in survival among patients receiving the combination therapy. Updated data from that trial presented yesterday confirmed that trend. At a median follow-up of 46.7 months, the median survival of patients receiving docetaxel/thalidomide was 25.9 months compared with 14.7 months in those patients receiving docetaxel alone.

Avi S. Retter, MD, clinical associate in genitourinary malignancies at the National Cancer Institute, Bethesda, MD, presented updated data from the NCI's docetaxel plus thalidomide versus docetaxel alone trial and data from a corollary study showing that a mutation in the P450 system did not appear to influence the combination therapy's activities.

"The take-home message is that this study was not empowered to detect survival benefits as a primary endpoint. With that disclaimer in mind, the combination of docetaxel and thalidomide has shown a significant survival difference in patients with androgen-independent cancer," Dr. Retter said.

Dr. Kibel cautioned against over-interpreting the results of phase II trials.

"We have proven that the toxicity is relatively low. However, even this level of toxicity can only be justified if there is a survival advantage," he said. "Currently our data is not mature enough to reach that conclusion."