Phase II, Multicenter, Randomized Trial of Docetaxel plus Prednisone with or Without Cediranib in Men with Chemotherapy‐Naive Metastatic Castrate‐Resistant Prostate Cancer.
In: Oncologist, Jg. 24 (2019-09-01), Heft 9, S. 1149-1149
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Lessons Learned: The negative results are consistent with the negative results of large phase III trials in which docetaxel plus antiangiogenic agents were used in patients with metastatic castrate‐resistant prostate cancer (mCRPC).The negative data underscore that, despite a sound biological rationale and supportive early‐phase clinical results, adding antiangiogenic agents to docetaxel for mCRPC is a great challenge. Background: Inhibition of vascular endothelial growth factor (VEGF) signaling abrogates tumor‐induced angiogenesis to constrain tumor growth, and can be exploited therapeutically by using cediranib, an oral tyrosine kinase inhibitor of VEGF receptor signaling. Our preliminary phase I trial data showed that adding cediranib to docetaxel plus prednisone (DP) was safe and feasible, with early evidence for efficacy in patients with metastatic castrate‐resistant prostate cancer (mCRPC). Methods: This multicenter phase II trial assessed whether adding cediranib to DP improves efficacy of DP in patients with mCRPC. Chemotherapy‐naive patients with mCRPC were randomly assigned to receive either docetaxel (75 mg/m2 intravenously every 3 weeks) with prednisone (5 mg twice daily) plus cediranib (30 mg once daily; the DP+C arm) or DP only (the DP arm). The primary endpoint was to compare 6‐month progression‐free survival (PFS) rate between the two arms. Secondary endpoints included 6‐month overall survival (OS), objective tumor and prostate‐specific antigen (PSA) response rates, biomarkers, and adverse events. Results: The 6‐month PFS rate in a total of 58 patients was only numerically higher in the DP+C arm (61%) compared with the DP arm (57%). Similarly, the 6‐month OS rate, objective tumor and PSA response rates, and biomarkers were not significantly different between the two arms. Increased baseline levels of interleukin 6 (IL‐6), however, were significantly associated with increased risk of progression. Neutropenia was the only grade 4 toxicity (38% in the DP+C arm vs. 18% in the DP arm). Conclusion: Combining cediranib with docetaxel + prednisone failed to demonstrate superior efficacy, compared with docetaxel + prednisone, and added toxicity. Our data do not support pursuing the combination further in patients with mCRPC. [ABSTRACT FROM AUTHOR]
经验总结 • 所得阴性结果与大型 III 期试验的阴性结果一致,此 III 期试验旨在研究多西他赛联合抗血管生成剂用于转移性去势抵抗性前列腺癌 (mCRPC) 患者的治疗效果。 • 阴性结果数据表明,尽管有完善的生物学原理和早期临床结果为依据,但在多西他赛中添加抗血管生成剂治疗mCRPC仍面临巨大的挑战。 摘要 背景。抑制血管内皮生长因子 (VEGF) 信号传导可消除肿瘤诱导的血管生成,从而抑制肿瘤生长,且可通过使用西地尼布(一种口服VEGF受体信号传导酪氨酸激酶抑制剂)进行治疗。我们初步的 I 期试验数据表明,在多西他赛联合泼尼松 (DP) 方案中加入西地尼布安全可行,且早期证据表明,这对于转移性去势抵抗性前列腺癌 (mCRPC) 患者有效。 方法。此项多中心 II 期试验对在 DP 方案中加入西地尼布能否改善 DP 方案对mCRPC患者的疗效进行了评估。对未接受化疗的mCRPC患者进行随机分配,接受多西他赛(75 mg/m2,每 3 周静脉注射一次)和泼尼松(5 mg,每日两次)联合西地尼布(30 mg,每日一次;DP+C 组)治疗或仅 DP(DP 组)治疗。主要终点是对比两组患者 6 个月无进展生存 (PFS) 率。次要终点包括确定 6 个月总生存 (OS) 率、客观肿瘤缓解率和前列腺特异性抗原 (PSA) 反应率、生物标志物及不良事件。 结果。在 58 例患者中,6 个月的PFS率在 DP+C 组 (61%) 中仅数值上高于 DP 组 (57%)。同样地,两组患者 6 个月的OS率、客观肿瘤缓解率和PSA反应率及生物标志物无显著差异。然而,白细胞介素 6 (IL‐6) 基线水平升高与疾病进展风险增加显著相关。中性粒细胞减少是唯一产生的 4 级毒性反应(DP+C 组为 38%,而 DP 组为 18%)。 结论。与多西他赛+泼尼松方案相比,西地尼布联合多西他赛+泼尼松的治疗方案并未显示出更好的疗效,且增加了毒性。我们的数据不支持对mCRPC患者实施进一步联合治疗。 [ABSTRACT FROM AUTHOR]
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Titel: |
Phase II, Multicenter, Randomized Trial of Docetaxel plus Prednisone with or Without Cediranib in Men with Chemotherapy‐Naive Metastatic Castrate‐Resistant Prostate Cancer.
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Autor/in / Beteiligte Person: | Heath, Elisabeth ; Heilbrun, Lance ; Mannuel, Heather ; Liu, Glenn ; Lara, Primo ; Monk, J. Paul ; Flaig, Thomas ; Zurita, Amado ; Mack, Philip ; Vaishampayan, Ulka ; Stella, Philip ; Smith, Daryn ; Bolton, Susan ; Hussain, Arif ; Al‐Janadi, Anas ; Silbiger, Daniel ; Usman, Muhammad ; Ivy, S. Percy |
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Zeitschrift: | Oncologist, Jg. 24 (2019-09-01), Heft 9, S. 1149-1149 |
Veröffentlichung: | 2019 |
Medientyp: | academicJournal |
ISSN: | 1083-7159 (print) |
DOI: | 10.1634/theoncologist.2019-0331 |
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