estramustine and Hematologic-Diseases

Estramustine, an agent with both hormonal and non-hormonal effects in men, is supposed to be effective in treating castration-resistant prostate cancer. However, previous studies have reported conflicting results. We conducted this meta-analysis to evaluate the efficacy and toxicity of additional estramustine to chemotherapy.. Data sources including PubMed, Medline, EMBASE, and Cochrane Controlled Trials Register were searched to identify potentially relevant randomized controlled trials. Prostate specific antigen (PSA) response, overall survival, and grade 3 to 4 toxicity were analyzed.. Seven randomized controlled trials, a total of 839 patients, were enrolled. The pooled odds ratio for PSA response was 3.02 (95% CI=1.69-5.39, P=.0002); the pooled hazard ratio for overall survival was .95 (95% CI=.80-1.14, P=.58); the pooled odds ratio for nausea/vomiting and cardiovascular toxicity were 3.90 (95% CI=1.05-14.45, P=.04) and 2.22 (95% CI=1.15-4.30, P=.02). No significant difference was detected for neutropenia, anemia, thrombocytopenia, diarrhea, fatigue, or neuropathy (P>.05).. According to this meta-analysis, chemotherapy with additional estramustine increased the PSA response rate. However, it increased the risk of grade 3 or 4 adverse effects such as nausea/vomiting and cardiovascular events, and the overall survival was not improved for castration-resistant prostate cancer patients.

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Cardiovascular Diseases; Combined Modality Therapy; Docetaxel; Epirubicin; Epothilones; Estramustine; Fatigue; Gastrointestinal Diseases; Hematologic Diseases; Humans; Male; Orchiectomy; Paclitaxel; Peripheral Nervous System Diseases; Prostate-Specific Antigen; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Salvage Therapy; Survival Analysis; Taxoids; Treatment Outcome; Vinblastine

Until the last few years very little information has been available regarding the potential of chemotherapy in prostatic cancer. Few drugs have been adequately tested to determine their efficacy, if any. Of the little conventional chemotherapy that has been documented, only diethylstilbestrol diphosphate (Stilphostrol, Honvan) has been safe, effective (at least in relieving bone pain) and available for repeat courses of treatment. The several well controlled clinical trials recently embarked upon and described in this article should reveal much about the effectiveness in prostatic cancer of agents already accepted in chemotherapy of other malignancies. Newer drugs will also require thorough testing. At this time no specific recommendations for chemotherpay other than the use of intravenous diethylstillbestrol diphospate can be made. Agents like estramustine phosphate (Estracyt) and flutamide (SCH-13521) with little to no bone marrow, liver, or renal toxicity are very promising. Studies of single-agent, sequential, and combined chemotherapy will necessarily lead to safe effective chemotherapy as adjuncts to surgery and/or radiotherapy for prostatic cancer in all stages.

Topics: Aged; Alkylating Agents; Antibiotics, Antineoplastic; Antimetabolites; Antineoplastic Agents; Bromocriptine; Cyproterone; Depression, Chemical; Diethylstilbestrol; Drug Therapy, Combination; Estramustine; Fluorouracil; Flutamide; Health Facilities; Hematologic Diseases; Humans; Kinetics; Male; Mitosis; Nitrogen Mustard Compounds; Prostatic Neoplasms

To evaluate prospectively the combination of a luteinizing hormone-releasing hormone analog with a somatostatin analog and dexamethasone in patients with hormone-refractory prostate cancer (HRPC) in a randomized Phase II study. HRPC presents a challenging therapeutic problem. Salvage chemotherapy is the usual approach at this stage of the disease. The combination of a luteinizing hormone-releasing hormone analog with a somatostatin analog and dexamethasone has produced objective clinical responses in HRPC.. Forty patients with HRPC were randomized to receive one of two treatments. Group 1 underwent chemotherapy (estramustine 140 mg three times daily and etoposide 100 mg orally for 21 days) and group 2 the combination of a somatostatin analog (lanreotide 30 mg intramuscularly every 14 days) and dexamethasone (4 mg tapered to 1 mg), in addition to androgen ablation by orchiectomy or a luteinizing hormone-releasing hormone analog (triptorelin 3.75 mg intramuscularly every 28 days). The clinical and prostate-specific antigen (PSA) response, overall survival, time to progression, and toxicity were compared between the two groups.. The data of 20 patients in group 1 and 18 in group 2 were analyzed. The demographic and clinical data were similar in the two groups at study entry. A PSA response (decrease of greater than 50%) was observed in 45% of group 1 and 44% of group 2. The difference was not statistically significant. A partial clinical response was observed in 29% and 30% of groups 1 and 2, respectively. Again, the difference was not statistically significant. Changes in performance status and pain score during treatment were not significantly different in the two groups. Hematologic toxicity was more frequent in group 1 (80% of patients), and mild diabetes was more frequent in group 2 (22% of patients). The overall survival was 18.8 months in group 1 and 18 months in group 2 (not statistically significant). The time to progression was 6 versus 4 months and, in the PSA responder subgroup, it was 8 versus 7.7 months in groups 1 and 2, respectively (neither difference was statistically significant).. The results of our randomized Phase II study indicated that the new combination treatment (luteinizing hormone-releasing hormone analog, somatostatin analog, and dexamethasone) may be equally effective as salvage chemotherapy in patients with HRPC in terms of the clinical and PSA response, overall survival, and time to progression. A larger prospective Phase III trial is required to confirm our observations.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Combined Modality Therapy; Dexamethasone; Diabetes Mellitus; Disease-Free Survival; Estramustine; Etoposide; Gastrointestinal Diseases; Gonadotropin-Releasing Hormone; Hematologic Diseases; Humans; Life Tables; Male; Middle Aged; Orchiectomy; Peptides, Cyclic; Prostatic Neoplasms; Somatostatin; Survival Analysis; Treatment Outcome; Triptorelin Pamoate

To evaluate the toxicity, efficacy, and pharmacokinetics of docetaxel when combined with oral estramustine and dexamethasone in a phase I study in patients with progressive metastatic androgen-independent prostate cancer.. Thirty-four men were stratified into minimally pretreated (MPT) and extensively pretreated (EPT) groups. Estramustine 280 mg PO tid was administered 1 hour before or 2 hours after meals on days 1 through 5, with escalated doses of docetaxel from 40 to 80 mg/m2 on day 2. Treatment was repeated every 21 days.. Thirty-four patients were assessable for toxicity and 33 for response. In the MPT patients, dose-limiting myelosuppression was reached at 80 mg/m2, with six patients experiencing grade 3/4 granulocytopenia. In EPT patients, escalation above 70 mg/m2 was not attempted. Fourteen MPT (70%) and six EPT (50%) patients had a > or = 50% decline in serum PSA on two consecutive measurements taken at least 2 weeks apart. The overall 50% PSA response rate was 63% (95% confidence interval [CI], 28% to 81%). Of the 18 patients with bidimensionally measurable disease, five (28%; 95% CI, 11% to 54%) achieved a partial response. At the time of entry onto the study, 15 patients required narcotic analgesics for bone pain; after treatment, eight (53%) discontinued their pain medications. The area under the curve for docetaxel increased linearly from 40 to 70 mg/m2. At 80 mg/m2, the measured area under the curve was 8.37 (standard deviation, 0.724), which was significantly higher than the previously reported values.. The recommended phase II dose of docetaxel combined with estramustine is 70 mg/m2 in MPT patients and 60 mg/m2 in EPT patients. This combination is active in men with androgen-independent prostate cancer.

Topics: Aged; Aged, 80 and over; Androgens; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Dose-Response Relationship, Drug; Estramustine; Gastrointestinal Diseases; Hematologic Diseases; Humans; Male; Middle Aged; Paclitaxel; Pain; Prostate-Specific Antigen; Prostatic Neoplasms; Survival Analysis; Taxoids

Combination antimicrotubule therapy with estramustine phosphate (EMP) and vinblastine has reproducible activity in metastatic hormone-refractory prostate cancer (HRPC) with an objective response rate of 31%. Although paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) by 24-hour infusion was inactive in HRPC, 0.5 to 1.0 nmol/L concentrations of paclitaxel combined with EMP exerted synergistic cytotoxicity in DU-145 androgen-independent human prostate cancer cell lines. Based on these results, we treated 24 patients with HRPC using the combination of paclitaxel 120 to 140 mg/m2 by 96-hour intravenous infusion every 3 weeks plus daily oral EMP at 600 mg/m2/d. Of seven patients with measurable soft tissue metastases, three have attained partial responses and a fourth patient is nearing partial response status. Of 16 patients with bone-only disease evaluated by change in serum prostate-specific antigen levels, 11 patients (68.8%) have had decreases of > or = 50% from pretreatment baseline. The prostate-specific antigen decrease has exceeded 80% in six of 16 (37.5%) patients. For all 23 evaluable patients, the prostate-specific antigen has decreased by > or = 50% in 15 (65.2%) and by > or = 80% in eight (34.7%). Grade 4 leukopenia occurred in one of 21 patients treated at the paclitaxel dose of 120 mg/m2/96 hr and one of three patients treated at 140 mg/m2/96 hr. The incidence of nausea (50%) and peripheral edema (37.5%) was similar to that associated with single-agent EMP. These results demonstrate that 96-hour paclitaxel plus EMP is active in HRPC and provide further evidence that the rational combination of antimicrotubule agents leads to synergistic antitumor activity in HRPC.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Diarrhea; Drug Administration Schedule; Drug Resistance, Neoplasm; Estramustine; Fatigue; Hematologic Diseases; Hormones; Humans; Male; Nausea; Paclitaxel; Prostate-Specific Antigen; Prostatic Neoplasms; Treatment Outcome

A prospective randomized trial for metastatic prostatic cancer in 220 patients who were refractory to hormone therapy was conducted by the National Prostatic Cancer Project from 1984 to 1985. As of July, 1986, the evaluation of these patients reflected no difference in response to either estramustine phosphate (Emcyt) or flutamide. Toxicities were minimal, and the observed survival and progression-free survival intervals were noteworthy in view of the overall prospects for such patients. Future studies dealing with specific quality of life issues seem to be indicated by our results.

Topics: Anilides; Carcinoma; Clinical Trials as Topic; Estramustine; Flutamide; Hematologic Diseases; Humans; Male; Nausea; Nitrogen Mustard Compounds; Prospective Studies; Prostatic Neoplasms; Random Allocation; Vomiting