Madan Ravi A, Karzai Fatima H, Ning Yang-Min, Adesunloye Bamidele A, Huang Xuan, Harold Nancy, Couvillon Anna, Chun Guinevere, Cordes Lisa, Sissung Tristan, Beedie Shaunna L, Dawson Nancy A, Theoret Marc R, McLeod David G, Rosner Inger, Trepel Jane B, Lee Min-Jung, Tomita Yusuke, Lee Sunmin, Chen Clara, Steinberg Seth M, Arlen Philip M, Gulley James L, Figg William D, Dahut William L
Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Lombardi Comprehensive Cancer Center, Georgetown University, Washington, D.C., USA.
BJU Int. 2016 Oct;118(4):590-7. doi: 10.1111/bju.13412. Epub 2016 Feb 19.
To determine the safety and clinical efficacy of two anti-angiogenic agents, bevacizumab and lenalidomide, with docetaxel and prednisone.
Eligible patients with metastatic castration-resistant prostate cancer enrolled in this open-label, phase II study of lenalidomide with bevacizumab (15 mg/kg), docetaxel (75 mg/m(2) ) and prednisone (10 mg daily). Docetaxel and bevacizumab were administered on day 1 of a 3-week treatment cycle. To establish safety, lenalidomide dosing in this combination was escalated in a conventional 3 + 3 design (15, 20 and 25 mg daily for 2 weeks followed by 1 week off). Patients received supportive measures including prophylactic pegfilgrastim and enoxaparin. The primary endpoints were safety and clinical efficacy.
A total of 63 patients enrolled in this trial. Toxicities were manageable with most common adverse events (AEs) being haematological, and were ascertained by weekly blood counts. Twenty-nine patients (46%) had grade 4 neutropenia, 20 (32%) had grade 3 anaemia and seven (11%) had grade 3 thrombocytopenia. Despite frequent neutropenia, serious infections were rare. Other common non-haematological grade 3 AEs included fatigue (10%) and diarrhoea (10%). Grade 2 AEs in >10% of patients included anorexia, weight loss, constipation, osteonecrosis of the jaw, rash and dyspnoea. Of 61 evaluable patients, 57 (93%), 55 (90%) and 33 (54%) had PSA declines of >30, >50 and >90%, respectively. Of the 29 evaluable patients, 24 (86%) had a confirmed radiographic partial response. The median times to progression and overall survival were 18.2 and 24.6 months, respectively.
With appropriate supportive measures, combination angiogenesis inhibition can be safely administered and potentially provide clinical benefit. These hypothesis-generating data would require randomized trials to confirm the findings.
确定两种抗血管生成药物贝伐单抗和来那度胺与多西他赛及泼尼松联合使用的安全性和临床疗效。
符合条件的转移性去势抵抗性前列腺癌患者参加了这项来那度胺联合贝伐单抗（15mg/kg）、多西他赛（75mg/m²）和泼尼松（每日10mg）的开放标签II期研究。多西他赛和贝伐单抗在3周治疗周期的第1天给药。为确定安全性，该联合用药中来那度胺的剂量按照传统的3+3设计逐步增加（每日15、20和25mg，持续2周，随后停药1周）。患者接受了包括预防性聚乙二醇化重组人粒细胞刺激因子和依诺肝素在内的支持性措施。主要终点为安全性和临床疗效。
共有63例患者参加了该试验。毒性反应可控，最常见的不良事件为血液学方面的，通过每周血常规检查确定。29例患者（46%）出现4级中性粒细胞减少，20例（32%）出现3级贫血，7例（11%）出现3级血小板减少。尽管中性粒细胞减少频繁，但严重感染罕见。其他常见的3级非血液学不良事件包括疲劳（10%）和腹泻（10%）。超过10%患者出现的2级不良事件包括厌食、体重减轻、便秘、颌骨坏死、皮疹和呼吸困难。在61例可评估患者中，分别有57例（93%）、55例（90%）和33例（54%）的前列腺特异性抗原（PSA）下降超过30%、50%和90%。在29例可评估患者中，24例（86%）有影像学证实的部分缓解。进展时间和总生存的中位时间分别为18.2个月和24.6个月。
采取适当的支持性措施后，联合血管生成抑制治疗可安全给药，并可能带来临床获益。这些产生假设的数据需要通过随机试验来证实研究结果。
