San Antonio--The foundation for a wider application of docetaxel (Taxotere) in prostate cancer is being laid, but it is far from complete. Two major studies appearing last year allowed the drug to replace mitoxantrone (Novantrone) as a first-line treatment in hormone-resistant metastatic prostate cancer. Data from a continuing phase II study of the agent as adjuvant therapy in radical prostatectomy patients at high risk of recurrence were presented here at the AUA annual meeting. Initial findings have shown that the drug is well tolerated, with reversible side effects.
"The bottom line is that docetaxel prolongs survival in metastatic disease, but with only a 2-month survival advantage," said co-author Adam S. Kibel, MD, referring to the earlier studies. "The goal now is to see if earlier treatment can provide a more robust survival advantage. Our phase II study demonstrates that adjuvant docetaxel-based chemotherapy is well tolerated.
The cycle was repeated six times. Median follow-up was 10 months: soon enough to determine toxicity, but too early to provide definitive data on efficacy.
All patients completed treatment. The only grade IV toxicity was hyperglycemia seen in two (2.6%) of the 77 patients. Patients presenting with grade III toxicity included six (7.8%) with hyperglycemia and four (5%) with dyspnea. Grade I/II toxicity, which appeared in more than 30% of the patients, included fatigue, alopecia, nail changes, diarrhea, dyspepsia, dyspnea, flushing, hyperglycemia, insomnia, nausea, and peripheral sensory neuropathy. One patient died of causes unrelated to the therapy.
"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. Unfortunately, at the current time, our data are not mature enough to reach that conclusion. This is not a treatment that I would recommend for routine care-at least not at this stage," Dr. Kibel told Urology Times.
More data to come
The effects that docetaxel might have on survival will not be known until the phase II trial concludes and the results can be compared with 77 controls whose disease characteristics match those of the patients in the current trial.
Definitive findings on the effects of docetaxel in high-risk patients should come from a large, international, multicenter trial being planned. Dr. Kibel described the trial as enrolling more than 2,000 prostate cancer patients at high risk for recurrence. The trial will be a two-by-two factorial design. Following surgery, patients considered to be at high risk for recurrence will be randomized to androgen deprivation or androgen plus docetaxel. The remaining patients will be followed. Those in this latter group who evidence biochemical failure (PSA >.2 ng/mL) will then be randomized to androgen deprivation or androgen deprivation plus docetaxel.