Comparison of Ketoconazole and Estramustine for Treating Patients with Castration-Resistant Prostate Cancer

PURPOSE: We investigated the efficacy of ketoconazole and estramustine before chemotherapy for treating patients with progressive castration-resistant prostate cancer (CRPC) after anti-androgen withdrawal syndrome. MATERIALS AND METHODS: Eighty-four patients who were diagnosed with CRPC and were treated between 2005 and 2009 were included. Thirty-nine patients were treated with 600 mg of ketoconazole and 10 mg of prednisolone per day (group I), and 45 patients were treated with 560 mg of estramustine per day (group II). The prostate-specific antigen (PSA) response, progression-free survival, and side effects were compared. RESULTS: The median age of the patients, PSA level, and follow-up period were 72 years, 48.5 ng/ml, and 4 months (range, 1 to 29 months), respectively. The overall PSA response rate was 35.7%, and the PSA response rates were 33.3% for group I and 37.8% for group II (p=0.672). The median progression-free survival times were 8 months (95% confidence interval [CI] 5.9-10.1) overall, 5 months (95% CI 1.6-8.3) in group I, and 8 months (95% CI 5.9-10.0) in group II (p=0.282). The most common complications in groups I and II were nausea and vomiting (51.3%) and anemia (77.8%), respectively. Nausea and vomiting and hepatotoxicity were observed more often in group I, and gynecomastia, neutropenia, and anemia were observed more often in group II. The toxicities of each adverse effect were < or =grade 2. CONCLUSIONS: With a resultant PSA decline and mild adverse effects, both ketoconazole and estramustine are worth consideration as treatment options for progressive CRPC patients after primary hormonal therapy.

Estramustine Phosphate Based Chemotherapy for Hormone Refractory Prostate Cancer / 대한비뇨기과학회지

PURPOSE: We wanted to evaluate the efficacy and side effects of estramustine monotherapy and estramustine plus etoposide or dexamethasone combined therapies for patients with hormone refractory prostate cancer(HRPC). MATERIALS AND METHODS: Between 2000 and 2004, 33 patients who were diagnosed with HRPC and treated with estramustine-based chemotherapy were evaluated. Eleven patients had oral estramustine monotherapy(group 1), 12 patients had oral estramustine plus oral etoposide(group 2), and finally 10 patients had oral estramustine plus oral dexamethasone(group 3). The prostate-specific antigen(PSA) response, progression-free survival and disease-specific survival were evaluated. RESULTS: The median patient age was 71 years and the median PSA was 97.3ng/ml. The median follow-up period was 17 months(range: 5-47). The overall response rate was 45.5%, and the response rate for each group was 36.4% for group 1, 41.7% for group 2 and 70.0% for group 3, respectively. The median time to progression(TTP) was 5 months(range: 1-16) overall and it was 5 months, 5.5 months and 5 months in groups 1, 2 and 3, respectively. Regarding the response rate, progression-free survival and disease specific survival, there were no statistically significant differences between the three groups(p>0.05). The most common hematologic complication was anemia that occurred in 28 patients and deep vein thrombosis occurred in 2. Severe toxicities(>or=grade 3) occurred in only 2 patients. CONCLUSIONS: Estramustine phosphate showed over a 45% response rates with less morbidities. Estramustine-based chemotherapy can be considered as an option for the treatment of HRPC. However, larger randomized controlled trials for regimens combined with other efficacious agents are necessary to elucidate the efficacy of chemotherapy for HRPC.

Dramatic Decline of PSA and Symptom Improvement after Estramustine Withdrawal in a Hormone-refractory Prostate Cancer Patient / 대한비뇨기과학회지

In some patients with prostate cancer and who manifest disease progression during maximal androgen blockade(MAB) therapy, discontinuation of antiandrogen treatment might result in a significant fall in the level of serum prostate-specific antigen(PSA), and this is often correlated with clinical improvement(antiandrogen withdrawal syndrome). However, a decline in the PSA level after the withdrawal of estramustine phosphate is extremely rare. We report here on a case of dramatic decline in the PSA level after withdrawal of estramustine phosphate in a patient with hormone refractory prostate cancer.

Does Intermittent low weekly doses of docetaxel-estramustine have an impact on treatment outcome in hormone refractory prostate cancer?

Although the majority of men with metastatic prostate cancer respond initially to and rogen ablation, most of them will eventually develop hormone-refractory progressive disease; with generally median survival less than one year from that point. The management of hormone refractory prostate cancer [HRPC] is challenging, as there is no uniformly accepted strategy. Combinations of estramustine and taxanes produced objective responses in soft tissue, reductions in serum PSA levels, and relief from bone pains. Different dosing and frequency of palliative chemo-hormonal therapy [docetaxel-estramustine] was evaluated in HRPC in relation to overall response, toxicity and survival. 21 patients with progressive, metastatic HRPC were r and omized to receive either [I] estramustine 280 mg PO tid, [Dl-5] with docetaxel as 70 mg/m[2] [1 hour infusion- D2] and recycling 3 weeks or [II] docetaxel 35 mg/m[2] [1 hour infusion] weekly for 3 consecutive weeks and estramustine 140 mg PO tid on days [Dl-3], [D8-10] and [D15-17] with recycling every 4 weeks. Primary endpoint was time to progression. However secondary endpoints were response rate, toxicity and survival. Twenty one patients were presented with a median age of 69 years [range, 49-78 years], median Gleason score of 8 [range, 6-10]. Metastases to bones and lymph nodes were present in 85.7% and 38.1% of total cases respectively. PSA response was statistically higher in weekly regimen than conventional schedule [75% vs. 44.4%], while partial response and pain relief was [22.2% vs. 33.3%] in conventional schedule compared to [44.4% vs. 50%] in weekly regimen respectively [p>0.05]. Median time to progression was [6.1 months vs. 5.6 months]; median survival [18.2 months vs. 16.5 months] and overall 1 year survival [77.8% vs. 66.7%] in conventional schedule vs. weekly regimen respectively. Grade III/IV of neutropenia occurred in 44.4% vs. 25% in conventional schedule treatment and weekly regimen respectively [p<0.05]. Neutropenic fever occurred only in one patient [11.1%] in conventional schedule group. Docetaxel-estramustine is a good effective combination of chemo-hormonal treatment used for hormonerefractory prostate cancer. Even though administration of lower weekly doses of doctaxel-estramustine does not seem to have statistically significant effect on time to disease progression and survival, but criteria of objective response rate with increase PSA response and measurable disease response and subjective improvement of pain are promising. Hematological toxicity, fatigue, fluid retention, attacks of thrombosis and neurotoxicities were lower in weekly regimen compared to conventional schedule. Nevertheless, the data presented here suggest that additional larger r and omized studies of [docetaxel plus estramustine] in lower doses and intermittent schedule are needed to better evaluate the efficacy and survival outcome of this regimen in men with HRPC

Fosfato de estramustina no tratamento do câncer da próstata resistente à hormonioterapia / Estramustine phosphate in the treatment of prostate cancer resistent to hormonal therapy

Vinte e três casos de câncer de próstata foram tratados com fosfato de estramustina na dose de 14mg/Kg/peso. Quatorze eram estádio clínico D2 e resistentes à hormonioterapia convencional. As respostas objetivas neste grupo de pacientes, seguidos pelo período médio de 12 meses, foi de 43%