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首页> 外文期刊>Patient Preference and Adherence >Update on treatment of follicular non-Hodgkin’s lymphoma: focus on potential of bortezomib
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Update on treatment of follicular non-Hodgkin’s lymphoma: focus on potential of bortezomib

机译：滤泡性非霍奇金淋巴瘤的治疗最新进展：关注硼替佐米的潜力

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Abstract: Follicular lymphoma is predominantly managed as a chronic disease, with intermittent chemo/immunotherapy reserved for symptomatic progression. It is considered incurable with conventional treatments, and current therapeutic options are associated with significant toxicities that are especially limiting in older patients. Bortezomib (PS-341; Velcade?), a first-in-class drug targeting the proteolytic core subunit of the 26S proteasome, has emerged as a therapeutic alternative in follicular lymphoma, with promising preclinical data and efficacy in patients with other hematological malignancies. Several clinical trials were conducted with bortezomib for the treatment of non-Hodgkin’s lymphoma. As a single agent, overall responses in follicular lymphoma varied greatly (16%–41%), with weekly bortezomib showing less neurotoxicity than twice-weekly regimens, but with concern about decreased responses. Combination with rituximab was projected to improve the efficacy of bortezomib, but this resulted in increased toxicities and questionable added benefit. Although the largest Phase III study in follicular lymphoma of bortezomib plus rituximab versus rituximab alone demonstrated a significant progression-free survival difference, the absolute difference was small (12.8 months versus 11 months). Combining bortezomib with established regimens, such as rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP), or rituximab-bendamustine also did not show definite benefit, and many of these studies did not meet their primary endpoint when bortezomib failed to improve responses or survival to the degree anticipated. In a disease where the goal of treatment is palliative and affected patients often have other medical and treatment-related comorbidities, decisions regarding therapies which carry risks of additional toxicities must be considered carefully. Conclusive evidence of the ability of bortezomib to improve patient outcomes meaningfully and to justify the added toxicity is lacking, but limitations in cross-trial comparisons are recognized. Large randomized trials and investigations of combinations with promising novel targeted agents will aid in determining the role of bortezomib, if any, in the future treatment of follicular lymphoma.
机译：摘要：滤泡性淋巴瘤主要作为一种慢性疾病进行管理，间歇性化学/免疫疗法可用于症状发展。它被认为是常规治疗无法治愈的，目前的治疗选择与明显的毒性有关，这在老年患者中尤为有限。 Bortezomib（PS-341; Velcade？）是针对26S蛋白酶体蛋白水解核心亚基的一流药物，已成为滤泡性淋巴瘤的替代治疗方法，在其他血液系统恶性肿瘤患者中具有可观的临床前数据和疗效。硼替佐米治疗非霍奇金淋巴瘤的多项临床试验。作为单一药物，滤泡性淋巴瘤的总体反应差异很大（16％–41％），硼替佐米每周的神经毒性低于每周两次，但担心反应降低。预计与利妥昔单抗联合使用可改善硼替佐米的疗效，但这会增加毒性并增加可疑的获益。尽管在硼替佐米加利妥昔单抗与单独使用利妥昔单抗的滤泡性淋巴瘤的最大的III期研究显示了无进展的生存期差异，但绝对差异很小（12.8个月对11个月）。将硼替佐米与已确立的方案如利妥昔单抗加环磷酰胺，阿霉素，长春新碱和泼尼松（R-CHOP），利妥昔单抗，环磷酰胺，长春新碱和泼尼松（R-CVP）或利妥昔单抗-贝达莫司汀联合使用也未显示明确的获益，并且当硼替佐米未能将疗效或生存率提高到预期水平时，其中许多研究未达到其主要终点。在治疗目标为姑息性疾病且受影响的患者经常患有其他与医学和治疗相关的合并症的疾病中，必须谨慎考虑关于可能带来其他毒性风险的疗法的决定。缺乏硼替佐米有效改善患者预后并证明增加毒性的能力的确凿证据，但人们认识到交叉试验比较的局限性。大型随机试验和与有前途的新型靶向药物联合使用的研究将有助于确定硼替佐米（如果有）在未来滤泡性淋巴瘤治疗中的作用。

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