Docetaxel with radiation in prostate cancer treatment

In 2004, the FDA approved docetaxel as the first chemotherapy drug proven to extend survival in metastatic hormone-refractory prostate cancer. Although the survival benefit was a modest 2.5 months, researchers launched clinical trials to determine whether the survival advantage could be increased by using docetaxel earlier in disease progression or by combining it with other therapies. Those trials are beginning to mature now.

Last year, the CHAARTED study demonstrated a 17-month survival advantage stemming from starting docetaxel at the same time as ADT in men with multiple metastases. However, another trial, GETUG-AFU 15, did not demonstrate a benefit. Last month, early reports of the STAMPEDE trial confirmed the benefit, which was 22 months among men with any metastases upon initial diagnosis. As in the CHAARTED trial, the evidence of benefit has not yet emerged among men with advanced cancer who did not yet evince metastases.

Two trials looked at combining docetaxel with radiation among men diagnosed with high risk localized prostate cancer. RTOG 0521 was recently reviewed in The “New” Prostate Cancer InfoLink. The 4-year overall survival was 89 percent without docetaxel and 93 percent with it — a statistically significant difference but perhaps not as meaningful as we would have liked to see. It’s possible that with longer follow up, the difference will increase in magnitude. Another clinical trial, GETUG-12, was designed to find out whether chemotherapy (docetaxel + estramustine) pretreatment would provide a survival benefit when added to 3 years of ADT and RT begun 3 months from the start of chemo (in 87 percent of the patients). The study was described and early results given here in 2010, so I will not go into the details again. However, some follow-up results have recently been published. Fizazi et al. report that 8-year relapse-free survival was 62 percent among those who received chemotherapy versus 50 percent among those who did not. They further report equal levels of late-term, high-grade side effects in both groups, and no deaths attributable to the chemotherapy.

Another randomized clinical trial (QRT SOGUG) has met its accrual targets, and hasn’t seen any dose-limiting toxicity from the combination of docetaxel, ADT, and external beam radiation.

While these are not yet the improvements in long-term survival that we eventually hope to see, they are encouraging. The long wait for differences in survival once again highlights the very long natural history of the disease, even in men diagnosed with high-risk prostate cancer.

Editorial note: This commentary was written for The “New” Prostate Cancer InfoLink by Allen Edel.

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