Platinum-based chemotherapy for variant castrate-resistant prostate cancer.
Platinum-based chemotherapy for variant castrate-resistant prostate cancer.
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DOI：
10.1158/1078-0432.ccr-12-3791
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发表时间：
2013-07-01
期刊：
影响因子：
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通讯作者：
Logothetis CJ
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文献类型：
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作者：
Aparicio AM;Harzstark AL;Corn PG;Wen S;Araujo JC;Tu SM;Pagliaro LC;Kim J;Millikan RE;Ryan C;Tannir NM;Zurita AJ;Mathew P;Arap W;Troncoso P;Thall PF;Logothetis CJ
小细胞前列腺癌（SCPC）（“间变性”）的临床特征通常在前列腺癌进展期间出现。我们试图确定铂类药物化疗在符合至少一个前瞻性定义的“间变性”临床标准的患者中的疗效，这些标准包括单纯内脏或主要溶解性骨转移、巨大肿瘤肿块、相对于肿瘤负荷的低PSA水平或对雄激素剥夺治疗的短反应。一项120例患者的一线卡铂和多西他赛（CD）与二线依托泊苷和顺铂（EP）的II期试验旨在根据贝叶斯概率模型提供可靠的临床应答估计值，并针对无效和毒性制定了提前停止规则。113例中有74例（65.4%）和71例中有24例（33.8%）分别在4个周期的CD和EP治疗后无进展。中位总生存期（OS）为16个月（95% CI，13.6-19.0个月）。在7个“间变性”标准中，巨大的肿瘤肿块与不良预后显著相关。乳酸脱氢酶（LDH）可强烈预测OS和快速进展。血清癌胚抗原（CEA）浓度强烈预测OS，但不能快速进展。神经内分泌标志物不能预测治疗结果或疗效。我们的研究结果支持这一假设，即“间变性”前列腺癌患者是一个可识别的子集，其特征是对含铂化疗的短期高反应率，类似于SCPC。我们的研究结果表明，CEA是有用的选择治疗男性CRPC和巩固治疗巨大的高级别肿瘤肿块，应考虑在这一患者群体。
Clinical features characteristic of small-cell prostate carcinoma (SCPC), (““anaplastic””) often emerge during the progression of prostate cancer. We sought to determine the efficacy of platinum-based chemotherapy in patients meeting at least one of seven prospectively defined “anaplastic” clinical criteria, including exclusive visceral or predominantly lytic bone metastases, bulky tumor masses, low PSA levels relative to tumor burden or short response to androgen deprivation therapy. A 120-patient phase II trial of frontline carboplatin and docetaxel (CD) and second-line etoposide and cisplatin (EP) was designed to provide reliable clinical response estimates under a Bayesian probability model with early stopping rules in place for futility and toxicity. Seventy-four of 113 (65.4%) and 24 of 71 (33.8%) were progression free after 4 cycles of CD and EP, respectively. Median overall survival (OS) was 16 months (95% CI, 13.6-19.0 months). Of the 7 “anaplastic” criteria, bulky tumor mass was significantly associated with poor outcome. Lactic acid dehydrogenase (LDH) strongly predicted for OS and rapid progression. Serum carcinoembryonic antigen (CEA) concentration strongly predicted OS but not rapid progression. Neuroendocrine markers did not predict outcome or response to therapy. Our findings support the hypothesis that patients with “anaplastic” prostate cancer are a recognizable subset characterized by a high response rate of short duration to platinum-containing chemotherapies, similar to SCPC. Our results suggest that CEA is useful for selecting therapy in men with CRPC and consolidative therapies to bulky high-grade tumor masses should be considered in this patient population.