A Controlled Trial of Leuprolide with and without Flutamide in Prostatic Carcinoma

Abstract

To test the hypothesis that maximal androgen blockade improves the effectiveness of the treatment of prostatic cancer, we conducted a randomized, double-blind trial in patients with disseminated, previously untreated prostate cancer (stage D2). All 603 men received leuprolide, an analogue of gonadotropin-releasing hormone that inhibits the release of gonadotropins, in combination with either placebo or flutamide, a nonsteroidal antiandrogen that inhibits the binding of androgens to the cell nucleus. As compared with the 300 patients receiving leuprolide and placebo, the 303 patients randomly assigned to receive leuprolide and flutamide had a longer progression-free survival (16.5 vs. 13.9 months; P = 0.039) and an increase in the median length of survival (35.6 vs. 28.3 months; P = 0.035). The differences between the treatments were particularly evident for men with minimal disease and good performance status; however, further studies should be conducted in this subgroup. Symptomatic improvement was greatest during the first 12 weeks of the combined androgen blockade, when leuprolide alone often produces a painful flare in the disease. We conclude that in patients with advanced prostate cancer, treatment with leuprolide and flutamide is superior to treatment with leuprolide alone.

Prognostic factors in Chinese patients with metastatic castration-resistant prostate cancer treated with docetaxel-based chemotherapy

“…2 Androgen deprivation therapy is the initial treatment for metastatic prostate cancer and leads to improvement in bone pain, regression of soft tissue metastases, and a reduction in serum levels of PSA. 3 Unfortunately, in virtually all patients, the disease inevitably advances to the androgen-independent stage within a median of 18-24 months after castration. 4 Two randomized phase III studies, SWOG 99-16 4 and TAX 327, 5 demonstrated that docetaxel-based chemotherapy confers a significant survival benefit of 20%-24% in patients with metastatic castration-resistant prostate cancer (mCRPC) compared with a mitoxantrone regimen.…”

Advanced prostate cancer

“…Crawford and associates 16 also showed a bene®t of early hormonal therapy in patients with distant metastasis. The MRC study 37 published in 1997 was a randomized study of 938 patients with locally advanced or asymptomatic metastatic prostate cancer.…”

“…15 Several studies have investigated CAB, but only two have shown a statistically signi®cant survival advantage over monotherapy. 16,17 CAB is most effective in patients with minimal disease and may have a subjective bene®t in those with symptomatic disease.…”

“…15 The superiority of CAB was documented by two major randomized studies. 16,19 Dijkman 20 also reported on a large double blind trial done on 457 patients randomized to placebo or nilutamide following orchiectomy. This study was designed to determine the long term ef®cacy and tolerability of nilutamide combined with orchiectomy in patients with advanced prostate cancer.…”

MRC study: when to commence treatment in advanced prostate cancer

“…As new developments such as LH RH analogues were perceived to have fewer disadvantages than older methods of hormone therapy, it was suggested that there was less reason to avoid treatment. 8 It also appeared that any bene®t from maximal androgen blockade appeared most marked in those with least disease, 9 reviving an old argument that as prostate cancer progresses it loses its hormone sensitivity. 2 Thus in the early part of this decade, opinion was once more in favour of immediate treatment.…”