Researchers from France have reported preliminary results of a Phase III randomized trial of neoadjuvant Taxotere® (docetaxel), Emcyt® (estramustine), and Zoladex® (goserelin) versus goserelin alone in men with high-risk prostate cancer. The details of this study were presented at the 2010 Genitourinary Cancers Symposium in San Francisco, March 5 to 7.[1] 

Men with localized prostate cancer can often be cured with surgery or radiation therapy alone. Men with certain risk factors—such as a high Gleason score, very high PSA level, spread of cancer outside the prostate, and lymph node involvement—have a high recurrence rate even if all detectable cancer is surgically removed, radiated, or both. There are several clinical trials, randomized and non-randomized, which suggest that the results of surgery and radiation therapy can be improved with androgen suppression before, during, and/or after therapy. However, an alternative approach is to use neoadjuvant and/or adjuvant chemotherapy. The two most active chemotherapy agents for the treatment of prostate cancer are Taxotere and Emcyt. Previous studies have suggested that the combination of Taxotere and Emcyt is more effective than Taxotere alone.

The current Phase III trial involved 413 patients with high-risk localized prostate cancer. “High-risk” was defined as one or more of the following risk factors: T3 or T4 stage, Gleason score of 8 or more, or a PSA greater than 20 ng/mL. All patients had a pelvic lymph node dissection. Patients were randomly allocated to treatment with neoadjuvant Zoladex alone or Zoladex plus Taxotere and estramustine. Chemotherapy was only given before definitive treatment for prostate cancer, while Zoladex was given for three years in both arms of the study. Local treatment was with radiation therapy in 87% of cases and, presumably, the remaining patients were treated with radical prostatectomy. Local treatment was delivered three months after neoadjuvant therapy.

• Toxicity of chemotherapy included grade 3-4 neutropenia in 27% and febrile neutropenia in 2%.
• There were no treatment-related deaths.
• Patients in the chemotherapy arm had fewer hot flashes than patients in the Zoladex alone arm (2% versus 22%, respectively).
• After three months of therapy, a serum PSA of 0.2 ng/mL or lower was observed in 34% of patients receiving chemotherapy plus Zoladex and 15% of patients receiving Zoladex alone.
• Patients receiving chemotherapy had transient decreases in quality-of-life scores.

Comments: This study is very important, as follow-up will allow for a definitive evaluation of the effects of neoadjuvant Taxotere and Emcyt in patients with high-risk prostate cancer.

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