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多西他赛和顺铂用于转移性雄激素非依赖性前列腺癌及循环神经内分泌标志物患者的治疗

Docetaxel and cisplatin in patients with metastatic androgen independent prostate cancer and circulating neuroendocrine markers.

作者信息

Culine Stéphane, El Demery Mounira, Lamy Pierre-Jean, Iborra François, Avancès Christophe, Pinguet Frédéric

机构信息

Centre Régional de Lutte Contre le Cancer Val d'Aurelle, Montpellier, France.

出版信息

J Urol. 2007 Sep;178(3 Pt 1):844-8; discussion 848. doi: 10.1016/j.juro.2007.05.044. Epub 2007 Jul 16.

Abstract

PURPOSE

A link between neuroendocrine cell differentiation and resistance to androgen deprivation has been observed in prostate cancer, suggesting the possible efficacy of specific treatments. We assessed the efficacy and toxicity of a chemotherapy regimen combining docetaxel and cisplatin in men with androgen independent prostatic adenocarcinoma and circulating neuroendocrine markers.

MATERIALS AND METHODS

A total of 41 patients were treated with a combination of 75 mg/m(2) docetaxel and 75 mg/m(2) cisplatin every 3 weeks for a maximum of 6 cycles. The primary study end point was the neuroendocrine response rate, defined as a decrease in neuron specific enolase and/or chromogranin A to 50% or greater of the supranormal baseline serum value. Median followup was 40 months.

RESULTS

A median of 6 cycles per patient was delivered. A neuroendocrine response was observed in 13 patients (33%). The median response duration was 4 months (range 2 to 10). The prostate specific antigen response rate was 48%. A clinical benefit was observed in 45% of patients who required analgesics at study entry. The objective response rate was 41% in 29 patients with measurable metastases. Five patients had to stop therapy due to toxicity. The main side effects were cumulative asthenia and sensitive neuropathy. Median survival was 12 months (range 1 to 38).

CONCLUSIONS

Regarding the disappointing efficacy and significant toxicity observed in this study, the combination of docetaxel and cisplatin cannot be recommended in daily practice. Further studies are necessary to determine whether patients with circulating neuroendocrine markers require specific therapeutic approaches.

摘要

目的

在前列腺癌中已观察到神经内分泌细胞分化与雄激素剥夺抵抗之间的联系,提示特定治疗可能有效。我们评估了多西他赛和顺铂联合化疗方案对雄激素非依赖性前列腺腺癌且伴有循环神经内分泌标志物的男性患者的疗效及毒性。

材料与方法

41例患者接受每3周一次的75mg/m²多西他赛与75mg/m²顺铂联合治疗,最多6个周期。主要研究终点为神经内分泌反应率,定义为神经元特异性烯醇化酶和/或嗜铬粒蛋白A降至高于正常基线血清值的50%或更低。中位随访时间为40个月。

结果

每位患者中位接受6个周期治疗。13例患者(33%)出现神经内分泌反应。中位反应持续时间为4个月(范围2至10个月)。前列腺特异性抗原反应率为48%。在研究入组时需要镇痛药物的患者中,45%观察到临床获益。29例有可测量转移灶的患者客观反应率为41%。5例患者因毒性不得不停止治疗。主要副作用为累积性乏力和感觉神经病变。中位生存期为12个月(范围1至38个月)。

结论

鉴于本研究中观察到的令人失望的疗效和显著毒性,在日常实践中不推荐多西他赛和顺铂联合使用。有必要进一步研究以确定伴有循环神经内分泌标志物的患者是否需要特定的治疗方法。

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