【汤森路透会议报道】ASCO 2014：仿制药吉西他滨联合激素疗法可延长生存期

2014-06-09 汤森路透生命科学与制药

                               
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内容来源：汤森路透

编译者：中国科学院上海生命科学信息中心 张永娟

说明：译文后附英文原文，若翻译有不明之处，请参见英文原文。

美国临床肿瘤学会（ASCO）2014年会大会报告：仿制药吉西他滨联合激素疗法可显著延长生存期

ASCO 2014大会的重要报告之一被称作E3805。该研究发现在标准激素疗法中添加吉西他滨（docetaxel）能够使那些刚被诊断为罹患激素敏感型PC（前列腺癌）的男性的寿命延长13个月，同时对已广泛扩散的癌症也有良好效果。

波士顿Dana-Farber癌症研究所泌尿生殖肿瘤学系Christopher Sweeney医生报道了E3805的相关数据。该研究参试包括那些癌细胞已经转移到骨、肺、肝脏的男性PC患者，且ADT（激素阻断疗法）已经无用，因此采用化学疗法。而作为首个批准治疗PC的化疗药物，吉西他滨于2004年5月面市。而对于这种药物是否能在PC早期起效未知，因而该研究团队设计了这项研究。

在实验中，790位新诊断为转移性PC的男性患者被随机分配为两组，一组接收ADT治疗，另一组接收ADT+吉西他滨治疗，治疗时长18周。约2/3的患者病情严重，当情况进一步恶化时，对45位接受ADT+吉西他滨治疗的患者增加了吉西他滨用量；而在仅实施ADT的小组，123位患者在疾病进展过程中加入了吉西他滨。在接下来的29个月中，ADT组的136位患者死亡，同时ADT+吉西他滨组死亡了101位患者，ADT组的总体存活时间中位数为44个月，而ADT+吉西他滨组为57.6个月。520位重症患者中的OS（总体生存时间）中位数也得到了提升，由32.2个月提升至49.2个月。病情相对轻患者的OS的数据没有完成，但目前看起来ADT+吉西他滨组优于ADT组。

PSA（前列腺特异抗体）、癌症转移情况以及症状恶化的情况证明了吉西他滨同时还能控制疾病进展。治疗一年后，PSA水平低于0.2 ng/ml（症状缓解的标志之一）的比例在两组之间发生了差异，ADT+吉西他滨组为22.7%，ADT组为11.7%。临床进展的中位数时间（即检测到新症状或新转移）也有明显差异，ADT+吉西他滨组为32.7个月，ADT组为19.8个月。

ASCO主席Clifford Hudis认为，这是一个对已有药物开发新用途的研究。而因为吉西他滨是一种仿制药物，将其应用进一步扩大，可明显降低药物成本，因此这项研究成果非常有价值。实际上，在前列腺癌的研究中从未出现过将存活期提高这么长的疗法，而在一般性实体肿瘤中，其存活期中位数也是相当长的了。

英文原文

Among the plenary studieshighlighted was one called E3805, an NIH-financed experiment that found addingdocetaxel to standard hormone therapy for men with newly diagnosed,hormone-sensitive prostate cancer (PC) extended survival by about 13 months,with an ever greater benefit in those with “high-extent” disease, i.e., cancerthat has spread extensively.

“This is an old-dog, new-tricksquestion,” conceded Hudis, noting that docetaxel is “ageneric drug that is available more broadly than ever before, withobviously reducing cost” – which makes the benefit findings even more valuable.“In prostate cancer, I’m not aware of a historical study that ever offered upthis magnitude of improvement in survival,” he said, and in solid tumorsgenerally, the median survival proved “almost unprecedented.”

Christopher Sweeney, doctor inthe genitourinary oncology department at Dana-Farber Cancer Institute inBoston, presented the data, which involved men whose disease has “moved fromprostate to bones, and less commonly, liver and lung,” and whoseandrogen-deprivation therapy (ADT) has failed, thus calling for chemotherapy.The first chemo agent approved for PC in this setting, docetaxel was clearedfor marketing in May 2004, branded Taxotere by Paris-based Sanofi SA.

“Ten years ago today, therewere two plenary sessions [at ASCO] showing docetaxel worked in that diseasespace,” Sweeney said. Scientists have since wanted to explore whether the drugworks in the early stage of PC, “hence this study design,” he said.

In the trial, 790 men withnewly diagnosed, metastatic PC were randomly assigned to receive either ADTalone or ADT with docetaxel over a period of 18 weeks. About two-thirds ofpatients had high-extent disease. When their conditions worsened, 45 patientsin the ADT plus docetaxel group got more docetaxel. In the ADT-only group, 123patients were given docetaxel at disease progression.

At a median follow-up of 29months, 136 deaths happened in the ADT-alone group vs. 101 in the ADT plusdocetaxel group. The median overall survival was 44 months in the ADT group and57.6 months in the ADT plus docetaxel group. The relative improvement in medianoverall survival (OS) turned up even larger among the 520 patients withhigh-extent disease (32.2 months vs. 49.2 months). Median OS for the subsetwith low-extent disease hasn’t been reached, since they respond better to ADT.

Docetaxel held diseaseprogression, too, as measured by a rise in prostate specific antigen (PSA), theappearance of new metastases, or the worsening of symptoms. At one year, theproportion of patients with PSA levels less than 0.2 ng/mL (a sign ofremission) reached 11.7 percent in the ADT group vs. 22.7 percent in the ADTplus docetaxel group. The median time to clinical progression – that is, newsymptoms or metastases detected on a scan – was 19.8 months in the ADT groupvs. 32.7 months in the ADT plus docetaxel group.

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