目的:最近的临床试验显示,联合使用聚ADP核糖聚合酶(PARP)抑制剂(PARP)和新型激素治疗(NHT)可改善转移性前列腺癌(mPC)男性患者的无进展生存期。美国的监管机构,加拿大,欧洲,日本最近批准了这种用于mPC的联合疗法。常见的不良事件(AE)包括疲劳,恶心和呕吐,和贫血。缺乏对这些组合的细微差别的AE管理指导。小组目标是就PARPi+NHT联合治疗的mPC患者的AE管理形成专家共识。
方法:使用RAND/加州大学洛杉矶分校改良的DelphiPanel方法。使用不良事件通用术语标准定义AE。十二名专家(七名医学肿瘤学家,一名高级执业注册护士,三位泌尿科医生,和一名患者倡导者)回顾了相关文献;以1-9量表对419例患者情景中怀疑引起AE的药物的初始AE治疗方案进行了独立评估;在2023年3月的会议上讨论了协议领域(AoA)和分歧领域(AoD);并在会议后重复了这些评级。第二轮评级构成了指导方针的基础。
■在第一轮和第二轮评分之间,AoD从41%下降到21%,就每个AE至少一个管理策略达成一致。AoAs包括:(1)对轻度AE患者继续对症治疗;(2)中度疲劳,推荐非药物治疗,暂时举行治疗,并在症状缓解时以减少的剂量重新开始;(3)严重恶心或任何程度的呕吐,其中对症治疗失败,暂时停止治疗,并在症状缓解后以减少的剂量重新开始;(4)血红蛋白7.1-8.0g/dl和贫血症状,暂时保持治疗,并在红细胞输血后以减少的剂量重新开始。
结论:本专家指南可支持接受PARPi+NHT联合治疗的mPC患者的AE管理。
结果:一组专家制定了转移性前列腺癌患者不良事件(AE)管理指南,该指南联合使用聚ADP核糖聚合酶抑制剂和新型激素治疗。对于轻度不良事件,建议在对症治疗的同时继续癌症治疗.对于中度或重度不良事件,癌症治疗应暂时停止,并在AE消退时以相同或减少的剂量重新开始.
OBJECTIVE: Recent clinical trials have shown improvement in progression-free survival in men with metastatic prostate cancer (mPC) treated with combination poly-ADP ribose polymerase (PARP) inhibitors (PARPi) and novel hormonal therapy (NHT). Regulatory bodies in the USA, Canada, Europe, and Japan have recently approved this combination therapy for mPC. Common adverse events (AEs) include fatigue, nausea and vomiting, and anemia. Nuanced AE management guidance for these combinations is lacking. The panel objective was to develop expert consensus on AE management in patients with mPC treated with the combination PARPi + NHT.
METHODS: The RAND/University of California Los Angeles modified Delphi Panel method was used. AEs were defined using the Common Terminology Criteria for Adverse Events. Twelve experts (seven medical oncologists, one advanced practice registered nurse, three urologists, and one patient advocate) reviewed the relevant literature; independently rated initial AE management options for the agent suspected of causing the AE for 419 patient scenarios on a 1-9 scale; discussed areas of agreement (AoAs) and disagreement (AoDs) at a March 2023 meeting; and repeated these ratings following the meeting. Second-round ratings formed the basis of guidelines.
UNASSIGNED: AoDs decreased from 41% to 21% between the first and second round ratings, with agreement on at least one management strategy for every AE. AoAs included the following: (1) continue therapy with symptomatic treatment for patients with mild AEs; (2) for moderate fatigue, recommend nonpharmacologic treatment, hold treatment temporarily, and restart at a reduced dose when symptoms resolve; (3) for severe nausea or any degree of vomiting where symptomatic treatment fails, hold treatment temporarily and restart at a reduced dose when symptoms resolve; and (4) for hemoglobin 7.1-8.0 g/dl and symptoms of anemia, hold treatment temporarily and restart at a reduced dose after red blood cell transfusion.
CONCLUSIONS: This expert guidance can support management of AEs in patients with mPC receiving combination PARPi + NHT therapy.
RESULTS: A panel of experts developed guidelines for adverse event (AE) management in patients with metastatic prostate cancer treated with a combination of poly-ADP ribose polymerase inhibitors and novel hormonal therapy. For mild AEs, continuation of cancer therapy along with symptomatic treatment is recommended. For moderate or severe AEs, cancer therapy should be stopped temporarily and restarted at the same or a reduced dose when AE resolves.