According to results from two trials presented at the 40th annual meeting of the American Society of Clinical Oncology (ASCO), Taxotere® (docetaxel)-based chemotherapy regimens improve survival compared to standard therapy in patients with hormone-refractory prostate cancer.

Chemotherapy for the treatment of androgen-independent prostate cancer has evolved over the past 20 years. Clinical trials in the 1980s and 1990s demonstrated single-agent treatments to be ineffective. In contrast, clinicians and investigators treating patients in the new millennium are faced with a variety of new targets and combinations. The combination of Novantrone® and a corticosteroid is considered to be a palliative standard of care; however, the median survival of this combination is still 11-12 months, which is similar to historical controls of single-agent chemotherapeutic agents.

Taxane-based therapy is a therapeutic modality which may improve survival, either alone or in combination with estramustine. Taxotere®, administered as a single agent weekly, has a response rate of 35-46%, as measured by a >50% PSA decline, and measurable responses in 17-20%. In contrast, patients treated with estramustine/Taxotere®-based regimens, as reported in phase II trials, have PSA decline rates and measurable disease response rates of 68-69% and 50-55%, respectively. The cost to the patient of increased anti-tumor activity when estramustine is added is toxicity, including deep venous thrombosis, peripheral edema, and asthenia.  At ASCO 2004 two randomized clinical trials clarified the role of Taxotere® for the treatment of hormone refractory prostate cancer.

The first clinical trial presented at ASCO compared Taxotere® and estramustine to the current standard regimen of Novantrone®/prednisone in 674 patients with hormone-refractory prostate cancer. Eighty percent of the patients in this trial had metastatic bone disease. Results demonstrated improved overall and progression-free survival with the Taxotere® regimen (see table 1). There was a 27% improvement in PFS and a 50% improvement in PSA response.

Table 1 Taxotere®/estramustine vs Novantrone®/prednisone in hormone-refractory prostate cancer

Severe side effects (grade 3-4) were more common in the group of patients treated with Taxotere®/estramustine, with the most frequent being gastrointestinal and cardiac.  Deaths related to treatment occurred in approximately 5% of patients, with no significant difference between the two treatments. The increased toxicity did not interfere with drug delivery in the Taxotere® group. Thus, it was concluded that the Taxotere® regimen decreased the risk of death by 20%.[1]

The second clinical trial compared 2 regimens of Taxotere®/prednisone to a standard regimen of Novantrone® plus prednisone in 1,006 patients with hormone-refractory prostate cancer. One group of patients received 75 mg/m2 or 30 mg/m2 every 3 weeks. The investigators concluded that the higher dose was more effective. Consequently, most of the comparisons that were presented at ASCO were between the 75 mg dose of Taxotere® and the Novantrone® regimen.  The 75 mg dose of Taxotere® increased median survival by 2.5 months over treatment with Novantron®/prednisone.

Table 2 Taxotere® vs Novantron®/prednisone in hormone-refractory prostate cancer

The most common severe side effect, leucopenia, was increased in patients treated with Taxotere®/prednisone.[2]

Comments: These results indicate that Taxotere®-based chemotherapy regimens improve survival over a historical standard treatment regimen, Novantrone® and prednisone, in the treatment of hormone-refractory prostate cancer. The researchers concluded that these are the largest comparative trials to date that have demonstrated an improvement in survival for initial treatment of hormone-refractory prostate cancer. There were no cost-benefit analyses presented, but the major problem with adopting Taxotere® over Novantrone® will likely be expense.

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