A phase II randomized trial of RAdium-223 dichloride and SABR Versus SABR for oligomEtastatic prostate caNcerS (RAVENS)
A phase II randomized trial of RAdium-223 dichloride and SABR Versus SABR for oligomEtastatic prostate caNcerS (RAVENS)
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DOI：
10.1186/s12885-020-07000-2
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发表时间：
2020-06-01
期刊：
影响因子：
3.8
通讯作者：
Tran, Phuoc T.
中科院分区：
文献类型：
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作者：
Hasan, Hamza;Deek, Matthew P.;Tran, Phuoc T.
背景与单纯全身治疗相比，转移导向治疗（MDT）与无进展生存期（PFS）和总生存期（OS）的改善相关。此外，在前列腺癌特异性队列中，与观察结果相比，MDT能够阻止前列腺癌敏感性寡转移性前列腺癌（HSOPCa）男性患者开始雄激素剥夺治疗（ADT）。虽然MDT在HSOPCa中似乎是安全有效的，但很大比例的男性最终会出现疾病复发。HSOPCa的失败模式表明患者在MDT后倾向于骨复发，提出了亚临床明显骨病的问题。镭-223二氯化物是一种放射性药物，与钙的结构相似，使其能够被骨吸收，在骨中释放α粒子，因此可能用于治疗微转移性骨病。因此，II期RAVENS试验的主要目的是评价MDT +镭-223二氯化物在延长HSOPCa男性患者无进展生存期方面的疗效。方法将患有HSOPCa和3个或3个以下转移灶（至少1个骨转移灶）的患者以1：1的比例随机分配至单独立体定向消融放射（SABR，也称为立体定向体部放射治疗（SBRT））组与SABR +镭-223二氯化物组，采用最小化算法来平衡机构、主要干预、既往激素治疗和PSA倍增时间的分配。SABR分1至5次给药，SABR +镭-223二氯化物组的患者将接受6次镭-223二氯化物输注，间隔4周。主要终点是无进展生存期。次要临床终点包括毒性和生活质量评估、12个月时的局部控制、局部进展、至远处进展的时间、至新转移的时间和缓解持续时间。讨论RAVENS试验将是第一个描述的II期、非盲、随机化研究，比较SABR +/-镭-223二氯化物治疗HSOPCa和3个或3个以下转移灶伴至少1个骨转移灶的患者。主要假设是SABR +镭-223二氯化物将使中位无进展生存期从SABR组的10个月增加至SABR +镭-223二氯化物组的20个月。
Background Metastasis directed therapy (MDT) for patients with oligometastatic disease is associated with improvements in progression free survival (PFS) and overall survival (OS) compared to systemic therapy alone. Additionally, within a prostate-cancer-specific cohort, MDT is able to forestall initiation of androgen deprivation therapy (ADT) in men with hormone-sensitive, oligometastatic prostate cancer (HSOPCa) compared to observation. While MDT appears to be safe and effective in HSOPCa, a large percentage of men will eventually have disease recurrence. Patterns of failure in HSOPCa demonstrate patients tend to have recurrence in the bone following MDT, raising the question of sub-clinically-apparent osseous disease. Radium-223 dichloride is a radiopharmaceutical with structural similarity to calcium, allowing it to be taken up by bone where it emits alpha particles, and therefore might have utility in the treatment of micrometastatic osseous disease. Therefore, the primary goal of the phase II RAVENS trial is to evaluate the efficacy of MDT + radium-223 dichloride in prolonging progression free survival in men with HSOPCa. Methods Patients with HSOPCa and 3 or less metastases with at least 1 bone metastasis will be randomized 1:1 to stereotactic ablative radiation (SABR, also known as stereotactic body radiation therapy (SBRT)) alone vs SABR + radium-223 dichloride with a minimization algorithm to balance assignment by institution, primary intervention, prior hormonal therapy, and PSA doubling time. SABR is delivered in one to five fractions and patients in the SABR + radium-223 dichloride arm will receive six infusions of radium-223 dichloride at four-week intervals. The primary end point is progression free survival. The secondary clinical endpoints include toxicity and quality of life assessments, local control at 12 months, locoregional progression, time to distant progression, time to new metastasis, and duration of response. Discussion The RAVENS trial will be the first described phase II, non-blinded, randomized study to compare SABR +/- radium-223 dichloride in patients with HSOPCa and 3 or less metastases with at least one bone metastasis. The primary hypothesis is that SABR + radium-223 dichloride will increase median progression-free survival from 10 months in the SABR arm to 20 months in the SABR + radium-223 dichloride arm.