Ross Robert W, Beer Tomasz M, Jacobus Susanna, Bubley Glenn J, Taplin Mary-Ellen, Ryan Christopher W, Huang Jiaoti, Oh William K
Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Cancer. 2008 Feb 1;112(3):521-6. doi: 10.1002/cncr.23195.
Prostate cancer is the second leading cause of cancer mortality among men in the U.S. To the authors' knowledge, there is no proven, effective, second-line therapy for docetaxel-refractory disease. Recent data suggest that platinum salts may be effective when combined with taxanes in metastatic hormone-refractory prostate cancer (HRPC). The authors conducted a phase 2 trial of docetaxel plus carboplatin chemotherapy in this disease setting.
Eligible men had metastatic HRPC that had progressed during or within 45 days after the completion of docetaxel-based chemotherapy. Patients were treated with intravenous docetaxel at a dose of 60 mg/m(2) plus carboplatin at an area under the curve of 4 once every 21 days until they had either disease progression or unacceptable toxicity.
Thirty-four patients were enrolled. Therapy was tolerated reasonably well; Grade 3 leukopenia (graded according to the Common Toxicity Criteria grading system) was the most common adverse event (experienced by 56% of patients), but there was only 1 episode of febrile neutropenia reported. Prostate-specific antigen (PSA) declines > or =50% were noted in 18% of patients, and measurable responses were observed in 14%. The median duration of PSA response was 5.7 months. The median progression-free survival was 3 months, and the median overall survival was 12.4 months. Patients were more likely to respond to the combination if they previously had responded to docetaxel.
In men with HRPC who developed progressive disease during or shortly after treatment with docetaxel, the addition of carboplatin resulted in modest additional activity. Taxane-refractory HRPC is an area of unmet need, and the current trial has provided evidence that platinum chemotherapy may be an important therapeutic option.
前列腺癌是美国男性癌症死亡的第二大主要原因。据作者所知，对于多西他赛难治性疾病，尚无经证实的有效二线治疗方法。最近的数据表明，铂盐与紫杉烷联合用于转移性激素难治性前列腺癌（HRPC）时可能有效。作者在此疾病背景下开展了一项多西他赛联合卡铂化疗的2期试验。
符合条件的男性患有转移性HRPC，在基于多西他赛的化疗期间或完成后45天内病情进展。患者接受静脉注射多西他赛，剂量为60mg/m²，联合卡铂，曲线下面积为4，每21天一次，直至出现疾病进展或不可接受的毒性。
34名患者入组。治疗耐受性较好；3级白细胞减少（根据常见毒性标准分级系统分级）是最常见的不良事件（56%的患者出现），但仅报告了1例发热性中性粒细胞减少症。18%的患者前列腺特异性抗原（PSA）下降≥50%，14%观察到可测量的反应。PSA反应的中位持续时间为5.7个月。中位无进展生存期为3个月，中位总生存期为12.4个月。如果患者之前对多西他赛有反应，则更有可能对联合治疗有反应。
对于在多西他赛治疗期间或之后不久出现疾病进展的HRPC男性患者，加用卡铂可带来适度的额外活性。紫杉烷难治性HRPC是一个未满足需求的领域，当前试验提供了证据表明铂类化疗可能是一种重要的治疗选择。
