Oh William K, Hagmann Elizabeth, Manola Judith, George Daniel J, Gilligan Timothy D, Jacobson Joseph O, Smith Matthew R, Kaufman Donald S, Kantoff Philip W
Lank Center for Genitourinary Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Massachusetts 02115, USA.
Clin Cancer Res. 2005 Jan 1;11(1):284-9.
To define the maximal tolerated dose, safety, and efficacy of docetaxel, carboplatin, and estramustine in patients with hormone-refractory prostate cancer (HRPC).
Patients with HRPC received docetaxel for 3 weeks, followed by a rest week. Docetaxel (20, 25, 30, 36, or 43 mg/m2) was given on days 2, 9, and 16 of a 28-day cycle. Patients also received estramustine (140 mg p.o. three times daily on days 1-5, 8-12, and 15-19) and carboplatin [area under the curve, AUC (5) or (6) on day 2].
Thirty patients were treated. Five patients received carboplatin [AUC (6)] but experienced delayed thrombocytopenia. After a protocol amendment, 25 subsequent patients received carboplatin [AUC (5)]. Median age was 64 years. Median prostate-specific antigen (PSA) was 117 ng/mL. Fifty-three percent received prior ketoconazole and 10% had mitoxantrone. No dose-limiting toxicities were noted. Although maximal tolerated dose was not reached, docetaxel dose escalation was stopped at 43 mg/m2. Significant myelosuppression was not seen until the highest dose level, when seven and four patients experienced grade 3 and 4 toxicities, respectively. Among all patients, PSA declines of > or =50% occurred in 63%. At the recommended phase II dose, PSA declines of > or =50% occurred in 75% (95% confidence interval, 43-95). Four of 14 (29%) patients with measurable disease had partial responses. Median survival was 14.6 months.
Estramustine, docetaxel, and carboplatin are well tolerated and active in HRPC. Myelosuppression is the primary toxicity. The recommended phase II dose of docetaxel is 43 mg/m2 combined with estramustine and carboplatin. PSA declines were seen at every dose level.
确定多西他赛、卡铂和雌莫司汀在激素难治性前列腺癌（HRPC）患者中的最大耐受剂量、安全性和疗效。
HRPC患者接受3周的多西他赛治疗，随后休息1周。在28天周期的第2、9和16天给予多西他赛（20、25、30、36或43mg/m²）。患者还接受雌莫司汀（第1 - 5天、8 - 12天和15 - 19天口服140mg，每日3次）和卡铂[第2天曲线下面积，AUC（5）或（6）]。
30例患者接受治疗。5例患者接受卡铂[AUC（6）]，但出现延迟性血小板减少。方案修订后，随后的25例患者接受卡铂[AUC（5）]。中位年龄为64岁。中位前列腺特异性抗原（PSA）为117ng/mL。53%的患者曾接受酮康唑治疗，10%的患者曾接受米托蒽醌治疗。未观察到剂量限制性毒性。尽管未达到最大耐受剂量，但多西他赛剂量递增在43mg/m²时停止。直到最高剂量水平才出现显著的骨髓抑制，此时分别有7例和4例患者出现3级和4级毒性。在所有患者中，63%的患者PSA下降≥50%。在推荐的II期剂量下，75%（95%置信区间，43 - 95）的患者PSA下降≥50%。14例可测量疾病患者中有4例（29%）出现部分缓解。中位生存期为14.6个月。
雌莫司汀、多西他赛和卡铂在HRPC中耐受性良好且有活性。骨髓抑制是主要毒性。多西他赛推荐的II期剂量为43mg/m²，联合雌莫司汀和卡铂。每个剂量水平均可见PSA下降。
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