Reviewer: Neha Vapiwala, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 7, 2004
Presenter: D.P. Petrylak
Presenter's Affiliation: SWOG
Type of Session: Plenary
The present-day standard of care in the treatment of AIPCA patients consists of the combination of mitoxantrone and prednisone for palliation of disease-related symptoms. There is no remarkable survival benefit with the use of these agents, and thus the ultimate prognosis of this patient group has remained dismal. Given this large roadblock in the treatment of AIPCA, attempts to define effective chemotherapeutic regimens that might help overcome this block are of particular clinical interest. Preclinical data have demonstrated a trend towards improved median survival with the combination of docetaxel and estramustine (Petrylak et al. JCO 17(3), 1999). This large intergroup collaboration was initiated in order to further examine the efficacy of D+E compared to the standard regimen of M+P in a randomized, phase III setting.
Materials and Methods
This year, two very pivotal studies have emerged regarding the optimal management of AIPCA patients. The study discussed here demonstrates the superiority of docetaxel and estramustine chemotherapy on survival and objective response as compared to the current standard of mitoxantrone and prednisone. The achievement of a survival benefit in this well-designed intergroup trial is revolutionary in terms of changing the paradigm of clinical AIPCA management. Firstly, this is the first large randomized study to detect a survival advantage in this group of patients that previously was "resigned" to receive palliative therapy with "soft", subjective endpoints. While the goal of alleviating patients' pain and obtaining subjective, symptomatic relief is certainly important, the results presented here encourage clinicians to reach for higher, more objective goals, namely improved survival.
Though modest (lengthened survival by ~2-2.5 months), the benefits with D+E are statistically significant and warrant further investigation in this area. Most of the higher grade 3/4 toxicity noted with this arm is attribued to the estramustine component of this doublet. The results of the European/Canadian TAX 327 trial, also presented at ASCO this year, show survival gains with the use of docetaxel monotherapy that are very comparable to those achieved here with docetaxel and estramustine. Given this fact, together with the higher rate of grade 3/4 toxicity seen because of the estramustine, some clinicians might make a valid argument for the omission of estramustine altogether. Future studies are likely to incorporate this hypothesis of docetaxel being the truly active agent, and the estramustine being unnecessary. In additon, several trials are ongoing and have been presented at ASCO this year on the use of docetaxel in conjunction with other non-chemotherapeutic agents, such as celecoxib, imatinib, etc.
The results from this study are likely to have a considerable impact on the referral and practice patterns of urologists in the US. Whereas patients with AIPCA might have traditionally undergone multiple trials of hormonal therapy, with only about 25% of them eventually being referred for chemotherapy, the data shown may very well alter that practice in the future. The old perception of AIPCA as a non-chemotherapy problem may slowly be replaced with one of a chemosensitive disease.
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