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1.
A Font A Murias F R García Arroyo C Martin J Areal J J Sanchez J A Santiago M Constenla J M Saladie R Rosell 《Annals of oncology》2005,16(3):419-424
BACKGROUND: Mitoxantrone/prednisone ameliorates symptoms in hormone refractory prostate cancer (HRPC) but has no effect on survival. Docetaxel (Taxotere)/estramustine improves response but with significant toxicity. We reasoned that a sequential administration of the two regimens could be a viable alternative for delivering full doses of chemotherapy, avoiding overlapping toxicity and preserving dose intensity. PATIENTS AND METHODS: Thirty HRPC patients were treated with mitoxantrone 10 mg/m(2), day 1, every 3 weeks, plus prednisone 5 mg twice daily, for three cycles, followed by estramustine phosphate, 280 mg three times daily, days 1 to 5, plus docetaxel 75 mg/m(2), day 2, every 3 weeks for a maximum of 10 cycles. RESULTS: All patients were assessable for response and toxicity. After mitoxantrone/prednisone treatment, the prostate-specific antigen (PSA) response rate was 23%, which increased to 63% after completion of sequential mitoxantrone/prednisone and docetaxel/estramustine treatment (12 partial and 7 complete responses). With a median follow-up of 18 months, median survival for all patients was 18 months, and median progression-free survival was 10 months. The mitoxantrone/prednisone regimen was well tolerated, and the only grade 3-4 toxicity was grade 3 neutropenia in four (13%) patients. Twenty-nine patients received a total of 173 cycles of docetaxel/estramustine (median, 6 cycles/patient). Six (20%) patients had grade 3-4 neutropenia and two (6%) patients had febrile neutropenia episodes. The most frequent non-hematological toxic effects were asthenia, nausea and vomiting, edemas and onycholysis. Two (6%) patients had deep venous thrombosis. CONCLUSIONS: Mitoxantrone/prednisone followed by docetaxel/estramustine is a well-tolerated and active regimen in HRPC. Sequential therapy is feasible and can be used to integrate novel, more active regimens. 相似文献
2.
Norihito Soga Manabu Kato Kouhei Nishikawa Yoshihiro Hasegawa Yasushi Yamada Hideaki Kise Kiminobu Arima Yoshiki Sugimura 《International journal of clinical oncology / Japan Society of Clinical Oncology》2009,14(2):130-135
Background We evaluated the efficacy and toxicity of intermittent docetaxel (DCT) with estramustine (EM) for hormone-refractory prostate
cancer (HRPC).
Methods Fifteen patients were enrolled. They received injected DCT (70 mg/m2 body surface) on day 1 in association with oral EM 560 mg/day (days 1–5). Treatments were repeated every 3 weeks. Serum prostate-specific
antigen (PSA) levels were categorized based on the first three courses. Patients exhibiting either a response or stable disease
(SD) could have a holiday from treatment (intermittent schedule). The holiday continued until elevation of the PSA level from
the nadir baseline level occurred three times. All patients were evaluated for toxicity and quality of life (QOL). Survival
curves were established using Kaplan-Meier graphs.
Results The median number of courses of DCT/EM therapy was five (range, 3–12 courses). The response rate of the first cycle was 53%:
3 patients with complete response (CR), 5 patients with partial response (PR), 4 patients with SD, and 3 patients with disease
progression. Eight patients were able to begin the second re-entry cycle. No patients showed a CR, 2 patients exhibited PR,
4 patients had SD, and the overall response rate was 25%. The survival rates were 93% at 1 year, and 26.1% at 2 years Grade
3–4 anemia was observed in 2 patients (13.3%), neutropenia in 11 (73.3%), and thrombocytopenia in 2 (13.3%). The QOL scale
showed good QOL after 6 months, with improvement in the score for nausea and vomiting.
Conclusion Intermittent DCT/EM therapy was well tolerated, and has the potential to prolong survival, with a high QOL, in patients with
HRPC. 相似文献
3.
Dose-finding study of weekly docetaxel plus estramustine in patients with hormone-refractory metastatic prostate cancer 总被引:1,自引:0,他引:1
OBJECTIVE: The aim of this phase I study was to find the maximum tolerated dose of weekly docetaxel in association with estramustine in hormone-refractory prostate cancer. METHODS: Eleven patients with hormone-refractory prostate cancer were treated with escalating weekly doses of docetaxel (level I, 3 patients, 30 mg/m2; level II, 3 patients, 35 mg/m2, level III, 3 patients, 40 mg/mz; level IV, 2 patients, 45 mg/m2) associated with fixed dosage of estramustine (840 mg/day). RESULTS: In level I, there was only one episode of grade 3 neutropenia; grade 1 nausea and vomiting were registered in 1 patient; in 1 patient mild edema of the lower limbs was noted. In level II, grade 2 stomatitis and grade 1 sensory symptoms occurred in 1 patient, and grade 1 edema in 1 case. In level Ill, grade 2 edema was noted in 2 patients, damage to nails in 1 patient, asthenia in 1 patient, grade 1 neuropathy in 2 patients, and grade 1 nausea in 1 patient. In level IV, grade 2 edema was present in 1 patient, grade 3 edema in 1 patient, changes with fall of nails and grade 2 erythema of face in 2 patients, asthenia in 2 patients, grade 1 neuropathy in both patients. Nine patients had a more than a 50% decrease in PSA after 2 cycles of therapy. CONCLUSIONS: The results of the study suggest a good tolerability of weekly 35 Mg/m2 docetaxel in hormone-refractory prostate cancer in association with estramustine. 相似文献
4.
Bracarda S Tonato M Rosi P De Angelis V Mearini E Cesaroni S Fornetti P Porena M 《Cancer》2000,88(6):1438-1444
BACKGROUND: Nearly all cases of metastatic prostate carcinoma progress, after hormonal ablation, to a hormone refractory status. To the authors' knowledge no standard chemotherapy for patients with hormone refractory prostate carcinoma (HRPC) exists. In a prospective study, the efficacy and toxicity of an oral combination of estramustine and cyclophosphamide were evaluated. METHODS: Between March 1996 and April 1998, 32 consecutive patients (median age 74 years; range, 53-84 years) with metastatic HRPC were treated with oral estramustine (10 mg/kg/day) and oral cyclophosphamide (2 mg/kg/day) for 14 days every 28 days. Inclusion criteria were previous complete androgen blockade, antiandrogen withdrawal evaluation, and clinical or biochemical disease progression. Response assessment was based on a decrease > or =50% in the prostate specific antigen (PSA) level associated with improvement (or no worsening) in Eastern Cooperative Oncology Group (ECOG) performance status (PS) and relief of bone pain (if present). RESULTS: All patients were evaluable for efficacy and toxicity. PSA levels decreased by at least 50% in 14 patients (43.7%) (95% confidence interval, 26.5-60.9), remained stable in 12 patients (37.5%), and rose in 6 patients (18.8%). ECOG PS was 0 in 5 of 14 patients, improved from 1 to 0 in 7 patients, and remained unchanged in 2 patients. Bone pain, present in 8 of 14 patients, disappeared in 7 and was partially relieved in 1. The median duration of response was 30 weeks (range, 8-88+ weeks). An objective partial response was obtained in two cases. Toxicity was mild and mainly gastrointestinal (World Health Organization [WHO] Grade 1). No cases of WHO Grade 3-4 hematologic toxicity occurred. CONCLUSIONS: The oral combination of estramustine and cyclophosphamide appears to be safe and effective in patients with HRPC. In responding patients its use shows a clinical benefit in terms of improvement of ECOG PS and pain control. 相似文献
5.
Noguchi M Mine T Yamada A Obata Y Yoshida K Mizoguchi J Harada M Suekane S Itoh K Matsuoka K 《Oncology research》2007,16(7):341-349
The aim of this study was to investigate prognostic factors of patients with metastatic hormone refractory prostate cancer (HRPC) under combined administration of personalized peptide vaccination and low-dose estramustine phosphate (EMP). From February 2001 to July 2004, 58 men with metastatic HRPC received the combination therapy of personalized peptide vaccination and low-dose EMP. Conducted immune monitorings for those patients were peptide-specific cytotoxic T lymphocyte (CTL) precursor analysis by interferon-gamma production and peptide-reactive immunoglobulin G (IgG) by an enzyme-linked immunosorbent assay. Clinical responses and survival times were also evaluated. The combination therapy was well tolerated with no major adverse effects. Increased levels of CTL precursors and IgG responses to the vaccinated peptides were observed in 29 of 37 (78%) patients and in 36 of 41 (88%) patients tested, respectively. A prostate-specific antigen decline of at least 50% occurred in 24% of patients. The median survival time was 17 months (95% confidence interval, 12-25 months). Cox proportional hazards analysis showed that a low number of lymphocytes (p = 0.0075, odds ratio 2.700), a negative immunological activity response after the vaccination (p = 0.0185, odds ratio 2.658), and poor performance status (p = 0.0347, odds ratio 2.569) were independent predictors of disease death. These encouraging results show the need for further evaluation of the combination of personalized peptide vaccination and low dose of EMP for metastatic HRPC patients. 相似文献
6.
J-C Eymard F Priou A Zannetti A Ravaud D Lepillé P Kerbrat P Gomez B Paule D Genet P Hérait E Ecstein-Fra?ssé F Joly 《Annals of oncology》2007,18(6):1064-1070
BACKGROUND: Docetaxel (Taxotere)-based regimens are the new standard therapy in advanced hormone-refractory prostate cancer (HRPC). A synergistic activity has been shown with docetaxel in combination with estramustine in vitro; however, the benefit of this combination remains controversial in clinical practice. We assessed the activity and safety of docetaxel alone and docetaxel-estramustine in HRPC. PATIENTS AND METHODS: Patients (n = 92) with metastatic HRPC and rising prostate-specific antigen (PSA) while receiving androgen suppression were randomized to 3-weekly treatment with either docetaxel 75 mg/m(2), day 1 (D), or docetaxel 70 mg/m(2), day 2, plus oral estramustine 280 mg twice daily, days 1-5 (DE). RESULTS: Ninety-one patients were treated (DE 47, D 44). A PSA response occurred in 68% (primary endpoint met) and 30% of patients, respectively. Median PSA response duration was 6.0 months in both groups. Median time to progression was 5.7 and 2.9 months, and median survival was 19.3 and 17.8 months in the DE and D arms, respectively. Hematologic and non-hematologic toxic effects were mild and similar in both arms. One patient in each group withdrew due to toxicity. Quality of life was similar in both groups. CONCLUSION: Combining estramustine with docetaxel in this schedule is an active and well-tolerated treatment option in HRPC. 相似文献
7.
Phase I trial of docetaxel with estramustine in androgen-independent prostate cancer. 总被引:9,自引:0,他引:9
D P Petrylak R B Macarthur J O'Connor G Shelton T Judge J Balog C Pfaff E Bagiella D Heitjan R Fine N Zuech I Sawczuk M Benson C A Olsson 《Journal of clinical oncology》1999,17(3):958-967
PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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. 相似文献
8.
健择加顺铂全身化疗治疗激素非依赖性晚期前列腺癌的近期疗效 总被引:2,自引:0,他引:2
背景与目的:迄今为止,临床上仍需探索有效的治疗措施治疗激素非依赖性晚期前列腺癌。本研究拟探讨健择加顺铂治疗激素非依赖性晚期前列腺癌的临床效果及不良反应。方法:15例激素非依赖性晚期前列腺癌患者,全部经手术去势及不同程度的抗雄激素药物治疗后病情缓解,之后病情再进展,经全身骨扫描证实12例有多发性骨转移灶,其中并有肝脏、双侧肾上腺和颅内转移各1例,血PSA进行性升高。用健择1000mg/m2加生理盐水(NS)100ml静脉滴注,第1、8天各一秦自科,等.健择加顺铂全身化疗治次;DDP100mg/m2加NS500ml静脉滴注第1天,或者DDP30mg+NS250ml静脉滴注第1~5天;每28天为一个疗程。结果:10例患者的血PSA值降至正常水平(<4ng/L),4例PSA值下降超过50%,1例PSA值变化不明显。化疗前12例有骨转移灶疼痛(按VRS分级Ⅰ级4例、Ⅱ级5例、Ⅲ级3例),化疗后9例疼痛消失,另3例仍有疼痛(Ⅰ级2例、Ⅱ级1例)。多发性颅内转移灶中最大转移瘤直径由化疗前的3.0cm缩小至0.5cm,化疗后面瘫症状消失。肝脏转移瘤由原先的10.2cm缩小至3.3cm。双侧肾上腺多发性转移瘤化疗后总的肿瘤体积缩小1/3以上。随访3~29个月,平均15.2个月,2例患者死亡,中位生存期14.7个月。平均疼痛缓解期为13.6个月。PSA值降低的平均稳定期为12.3个月。本组病例最常见 相似文献
9.
W. Kreis D. R. Budman J. Fetten A. L. Gonzales B. Barile V. Vinciguerra 《Annals of oncology》1999,10(1):33-38
Background: To apply our preclinical findings of cytotoxic synergy with the combination of estramustine phosphate (EP) and docetaxel as the basis of treatment of hormone refractory metastatic prostate cancer in man. To determine the optimal dosage and the toxicities of these two agents for future trials.Patients and methods: Seventeen patients with hormone refractory metastatic prostate cancer who were ambulatory with performance status 2, normal marrow, renal and hepatic function were entered. Prior exposure to EP or a taxane were exclusion factors. EP was given orally at a dose of 14 mg/kg of body weight daily with concurrent docetaxel administered every 21 days as an intravenous infusion over 1 hour with dexamethasone 8 mg. PO BID for five days. EP dosages were kept static; docetaxel dosages were explored in a minimum of three patients per level for dosages of 40, 60, 70, and 80 mg/m2. Patients were evaluated weekly. Prostate specific antigen (PSA) was measured every three weeks.Results: Five patients were entered at a docetaxel dose of 40 mg/m2, three at 60 mg/m2, six at 70 mg/m2, and three at 80 mg/m2. Only one patient had received prior chemotherapy. Grades 1 or 2 hypocalcemia and hypophosphatemia were seen at all dosage levels. Other grade 2 or less toxicities not related to dosage included alopecia, anorexia, stomatitis, diarrhea, and epigastric pain. Dose limiting toxicities (DLT) as grade 4 leukopenia and grade 4 fatigue were seen at 80 mg/m2. The phase II dose was defined at 70 mg/m2 with rapidly reversible leukopenia and minor liver function abnormalities. At this dosing level, dose intensity was 88% and 86% over consecutive cycles for docetaxel and EP, respectively. Two vascular events occurred at this dose level (70 mg/m2): one arterial and the other venous. PSA decreases greater than 50% from baseline were seen in 14 of 17 patients at all dosage levels. Four of the 17 patients demonstrated a complete biochemical response (PSA 4 ng/ml). One patient had a partial response with measurable lung and liver lesions.Conclusion: EP given continuously with every three-week docetaxel at a dose of 70 mg/m2 is tolerable with evidence of antitumor activity based upon significant declines in PSA in the majority of patients and improvement of lung metastasis in one patient. Larger phase II studies of this combination in a homogenous population are warranted. 相似文献
10.
Carles J Font A Mellado B Domenech M Gallardo E González-Larriba JL Catalan G Alfaro J Gonzalez Del Alba A Nogué M Lianes P Tello JM 《British journal of cancer》2007,97(9):1206-1210
The objective of this study was to evaluate the efficacy and safety profile of weekly docetaxel, estramustine and celecoxib in patients with advanced hormone-refractory prostate cancer. Forty-eight patients received 35 mg m(-2) of weekly docetaxel for 3 out of every 4 weeks, 280 mg of estramustine twice daily on days 1-3, 8-10, 15-17 and 400 mg of celecoxib twice daily until progression or toxicity. Cycles were repeated every 28 days for at least six cycles. Patients were evaluated for response and toxicity. Patients received a median of four cycles (range: 1-9). On an intention-to-treat analysis, prostate-specific antigen (PSA) was decreased greater than 50% in 28 out of 48 patients (overall response rate: 58%, 95% confidence interval (CI): 44-72) and median duration of PSA response was 8.0 months (95% CI: 6.9-9.0). After a median follow-up of 11.3 months, the median time to progression was 7.1 months and the median overall survival was 19.2 months. The most frequent severe toxicity was asthenia (15% of patients), diarrhoea and stomatitis (8% of patients, each). Grade 3/4 neutropenia was reported in two patients. There was a toxic death during the study due to a gastric perforation. Celecoxib with weekly docetaxel and estramustine is an effective and safe treatment for patients with hormone-refractory prostate cancer, but it does not seem to add any benefit to docetaxel. 相似文献
11.
BACKGROUND: The objective of the current study was to determine the histologic and molecular changes that occurred in patients with high-risk, localized prostate cancer (PCa) after neoadjuvant docetaxel chemotherapy. METHODS: Patients who had locally advanced PCa (serum preoperative [initial] prostate-specific antigen [iPSA] level >or=15 ng/mL, or clinical >or=T2b disease, or biopsy Gleason score [GS] >or=8) and no evidence of metastatic disease received 6 doses of intravenous docetaxel (40 mg/m(2)) administered weekly for 6 weeks followed by radical prostatectomy (RP). The Wilcoxon signed-rank test was used to compare pretreatment and posttreatment markers. RESULTS: Twenty-eight patients completed chemotherapy and underwent RP at the Cleveland Clinic; none achieved a pathologic complete response. Pretreatment diagnostic prostate biopsies (PBx) were reviewed in all patients, and unstained sections of formalin-fixed tissue were available from 11 patients. The median patient age was 62 years (range, 49-72 years), and the median iPSA was 6.8 ng/mL (range, 2.5-24 ng/mL). At a median follow-up of 49.5 months (range, 23-72 months), 12 patients (43%) remained clinically and biochemically free of disease with no additional therapy, and 16 patients (57%) had biochemical failure. The pretreatment GS was 6 in 2 patients (7%), 7 in 10 patients (36%), 8 in 11 patients (39%) and 9 in 5 patients (18%). Two patients (7.1%) had organ-confined disease, and 23 patients (82.1%) had extraprostatic extension. Four patients (14.3%) had positive lymph nodes, and 11 patients (39.3%) had seminal vesicle involvement. Immunohistochemical (IHC) staining for a panel of markers involved in various cellular functions (alpha-methylacyl-coenzyme A racemase [AMACR], beta-tubulin I, beta-tubulin III, cyclin D1, p27, p21, Ki-67, p53, Bcl-2, and an apoptosis detection kit [ApopTag]) was performed on a tissue microarray that contained the posttreatment (RP) tissue specimens and on the PBx specimens, if available. When the IHC staining patterns were compared between PBx and RP specimens using the Wilcoxon signed-rank test, only p53 expression (P = .017) and Bcl-2 expression (P = .014) were found to be increased significantly after neoadjuvant docetaxel treatment. However, after performing the Bonferroni adjustment, these differences were no longer significant (P > .005). Ki-67, ApopTag, beta-tubulin I, and beta-tubulin III expression levels also were increased after treatment; however, the differences were not found to be statistically significant. The expression levels of AMACR, p27, p21, and cyclin D1 were comparable in pretreatment and posttreatment specimens. CONCLUSIONS: The current results indicated that, although it will require longer follow-up studies and larger numbers of patients to ascertain the value of neoadjuvant treatment, the negative findings of the current study may explain the lack of clinical response in patients who received neoadjuvant docetaxel for PCa. Although the results were subject to interpretation limits based on the study size, the increased expression of p53 and Bcl-2 that was detected after treatment using the Wilcoxon signed-rank test suggested that the apoptotic pathway may be an important target for this drug, and further investigation is warranted. 相似文献
12.
Narita S Tsuchiya N Yuasa T Maita S Obara T Numakura K Tsuruta H Saito M Inoue T Horikawa Y Satoh S Habuchi T 《International journal of clinical oncology / Japan Society of Clinical Oncology》2012,17(3):204-211
Objectives
Docetaxel-based chemotherapy is effective in patients with castration-resistant prostate cancer (CRPC). This phase II study assessed the outcome and predictive factors for prognosis and toxicity following intermittent chemotherapy with docetaxel, estramustine phosphate, and carboplatin (DEC) in patients with CRPC.Methods
Thirty-five patients were treated with a DEC regimen that consisted of a 28-day cycle of drugs as follows: docetaxel (60?mg/m2 on day 1), carboplatin (AUC 5 on day 1) and estramustine phosphate (560?mg daily). Treatment was continued intermittently. The end point was to test the effect of DEC on the response rate and overall survival (OS). Statistical correlations between the outcomes and predictive factors, including clinical parameters and 8 single-nucleotide polymorphisms (SNPs) related to drug metabolism, were assessed.Results
Prostate-specific antigen levels decreased by more than 30% in 65.7% of the patients. The median OS following DEC was 17.8?months, and the median total time of chemotherapy holiday was 7.7?months (range 1.7?C35.8). On multivariate analysis, serum lactate dehydrogenase (LDH) was an independent prognostic factor for OS (p?=?0.007). On SNP analysis, patients carrying the TT genotype of the ABCB1 C3435T polymorphism showed a significantly more severe leukocytopenia during the first cycle of DEC therapy compared to patients with the CC?+?CT genotype (p?=?0.036).Conclusion
Combination chemotherapy with DEC has a potential effect on CRPC with acceptable toxicity. Serum LDH may be a promising predictor of prognosis, and the ABCB1 C3435T polymorphism may be a genetic predictor of the severity of leukocytopenia in patients with CRPC treated with DEC. 相似文献13.
14.
Koji Hatano Kazuo Nishimura Yasutomo Nakai Takahiro Yoshida Mototaka Sato Atsunari Kawashima Masatoshi Mukai Akira Nagahara Motohide Uemura Daizo Oka Masashi Nakayama Hitoshi Takayama Kiyonori Shimizu Norio Meguro Tsuyoshi Tanigawa Seiji Yamaguchi Akira Tsujimura Norio Nonomura 《International journal of clinical oncology / Japan Society of Clinical Oncology》2013,18(4):704-710
Background
A low-dose chemotherapy consisting of docetaxel, estramustine and dexamethasone was investigated for its beneficial effect and feasibility in Japanese patients with metastatic castration-resistant prostate cancer (CRPC).Methods
Seventy-two Japanese patients with metastatic CRPC were enrolled to receive docetaxel (25 mg/m2 on days 2 and 9), estramustine phosphate (280 mg orally twice daily from day 1 to day 3 and from day 8 to day 10) and dexamethasone (0.5 mg orally twice daily) every 21 days.Results
The median age of the patients was 72 years and 64 patients (89 %) had ≥grade 1 anemia at entry. The median total number of courses administered was 8.5 (range 1–93). Forty-two patients (58 %) had a prostate-specific antigen (PSA) decline of ≥50 %. The median progression-free survival and overall survival were 6 and 23 months, respectively. Fifteen patients (21 %) improved and 53 patients (74 %) were stable in their performance status. Of the 40 patients with bone pain, 25 patients (63 %) showed pain reduction. Among 71 patients assessable for their hemoglobin levels, 21 patients (30 %) achieved an increase of at least 1.0 g/dl. Of the 5 patients who terminated treatment because of ≥grade 3 toxicity, 4 patients had pneumonitis and one patient had anemia. Only one patient developed ≥grade 3 neutropenia.Conclusions
The low-dose combination of docetaxel, estramustine and dexamethasone is active and tolerable with beneficial effects on serum PSA levels, performance status, anemia and bone pain in Japanese patients with CRPC. This regimen is a reasonable option for elderly patients with bone disease at risk of hematologic toxicity. 相似文献15.
目的 探讨去甲斑蝥素联合紫杉醇对激素抵抗性前列腺癌(HRPC)患者的临床疗效及安全性.方法 选择90例HRPC患者,依据随机数字表法将患者分为试验组(n=45)和对照组(n=45),试验组患者接受去甲斑蝥素联合紫杉醇化疗,对照组患者接受紫杉醇单药化疗.分析比较两组患者的疗效、生存情况及不良反应发生情况.结果 试验组患者的总有效率为82.2%(37/45),高于对照组的46.7%(21/45),差异有统计学意义(P﹤0.05).试验组患者的累积生存率为44.4%,中位生存时间为21.9个月(18.5~25.3个月);对照组患者的累积生存率为28.9%,中位生存时间为18.9个月(15.9~21.9个月),组间比较差异有统计学意义(P﹤0.05).试验组患者的好转情况明显优于对照组,差异有统计学意义(P﹤0.01).两组患者的不良反应发生情况比较,差异无统计学意义(P﹥0.05).结论 去甲斑蝥素联合紫杉醇对HRPC患者的临床疗效显著,且安全性好. 相似文献
16.
Dawson NA Halabi S Ou SS Biggs DD Kessinger A Vogelzang N Clamon GH Nanus DM Kelly WK Small EJ;Cancer Leukemia Group B 《Clinical genitourinary cancer》2008,6(2):110-116
PURPOSE: Docetaxel/estramustine is a known active regimen in hormonerefractory prostate cancer (HRPC). A phase II study was conducted to assess the safety and efficacy of docetaxel/estramustine combined with exisulind, an apoptotic antineoplastic drug. PATIENTS AND METHODS: Eighty men with chemotherapy-naive HRPC were enrolled in a multicenter, cooperative group study. The treatment regimen consisted of oral estramustine (280 mg 3 times daily for 5 days), docetaxel 70 mg/m2, oral exisulind (250 mg twice daily), oral dexamethasone (8 mg twice daily for 3 days), and oral warfarin (2 mg daily). RESULTS: Seventy-five eligible patients were treated with a median of 6 cycles of therapy. Fortyseven patients (62.7%; 95% CI, 50.7%-73.6%) had a > or = 50% decline in prostate-specific antigen levels. Forty-six patients had measurable disease with 6 partial responses (13%; 95% CI, 4.9%-26.3%). The main grade 3/4 toxicities were neutrophils (79%), fatigue (15%), and thrombosis/embolism (10%). The median time to first progression was 5.1 months (95% CI, 4.4-6.3 months) and the median survival time was 17.8 months (95% CI, 14.7-20.1 months). CONCLUSION: The combination of estramustine/docetaxel/exisulind was associated with significant thomboembolic toxicity despite prophylactic warfarin. The contribution of exisulind to toxicity is uncertain. Prostate-specific antigen decline, response rates, and progression-free and overall survival are similar to those reported with docetaxel/estramustine. 相似文献
17.
预后较差的激素非依赖性的前列腺癌,目前的治疗方法主要是化疗.米托蒽醌和雌莫司汀都是已经FDA批准的可以用于治疗前列腺癌的化疗药物.两种药物与单用激素相比,未延长患者的生存时间.2004年全美临床肿瘤年会(ASCO)上,报告了两项多西紫杉醇联合化疗治疗激素难治性前列腺癌的临床研究,结果显示能明显改善生存. 相似文献
18.
Dreicer R 《Hematology / Oncology Clinics of North America》2006,20(4):935-46, x
To place appropriately into context the current status of chemotherapy as a management option for patients with hormone-refractory metastatic prostate cancer, it is important to reflect on the widely held historical belief that advanced prostate cancer is a chemotherapeutic-insensitive neoplasm. This article focuses on three disease subsets: (1)metastatic, hormone-refractory, chemotherapy-naive prostate cancer;(2) metastatic, hormone-refractory, progressive prostate cancer after frontline chemotherapy; and (3) locally advanced prostate cancer.Yagoda and Petrylak evaluated the results of 26 phase II trials of antineoplastics in advanced prostate cancer published between 1987 and 1991 and found the average objective response rate was less than 10% with only a few studies having response rates in the 10% to 20%range. 相似文献
19.
PRECIS: Estramustine 600 mg/m2 can be administered safely with 225 mg/m2 of paclitaxel if administered as a 3-hr infusion for the treatment of hormone refractory prostate cancer. Significant anti-tumor activity has been reconfirmed despite the change in schedule of administration of the paclitaxel. PURPOSE: This phase I study was conducted to identify the maximum tolerated dosage of paclitaxel administered as a 3-hr infusion combined with a stable dosage of estramustine capsules daily in men with hormone refractory prostate cancer. A secondary endpoint was to assess anti-tumor efficacy in this targeted patient population. PATIENTS AND METHODS: Twenty-six male patients, all with hormone refractory prostate cancer were enrolled in this trial. Estramustine was administered at a dosage of 600 mg/m2 daily, and paclitaxel was dose-escalated in cohorts from 125 to 250 mg/m2 administered as an infusion over 3 hr every 21 days. Patients were treated until maximum response was achieved, or toxicity or progressive disease precluded further treatment. Toxicity to determine maximum tolerated dose was assessed only during the first 3-week cycle. RESULTS: The maximum tolerated dose of paclitaxel on this schedule was 225 mg/m2 based on unacceptable dose-limiting fatigue observed at the next higher dosage level. Other grade 3 or 4 events included myelosuppression, left ventricular dysfunction, elevated liver function tests, deep venous thrombosis, vomiting, and development of depression. Using a response criteria of prostate specific antigen decline of > 50% persisting for a minimum of 6 weeks, eight of 26 patients responded (30.8%). Two of seven patients with documented soft-tissue disease experienced > 50% reductions in size of lesions or number of sites. The median response duration was 6 months, and the median survival time was 16 months. CONCLUSION: The recommended phase II dose of paclitaxel is 225 mg/m2 when administered over 3 hr in combination with estramustine. This regimen has an acceptable toxicity profile, is a convenient schedule, and results in significant antitumor activity even in a heavily pre-treated population of patients. 相似文献
20.
Yasutomo Nakai Kazuo Nishimura Masashi Nakayama Motohide Uemura Hitoshi Takayama Norio Nonomura Akira Tsujimura 《International journal of clinical oncology / Japan Society of Clinical Oncology》2014,19(1):165-172