Medical Oncology Unit, San Filippo Neri Hospital, 00135 Roma, Italy.
Department of Sciences and Technologies, University of Sannio, 82100 Benevento, Italy.
World J Gastroenterol. 2017 Aug 28;23(32):5875-5886. doi: 10.3748/wjg.v23.i32.5875.
Pancreatic cancer (PDAC) is an aggressive and chemoresistant disease, representing the fourth cause of cancer related deaths in western countries. Majority of patients have unresectable, locally advanced or metastatic disease at time of diagnosis and the 5-year survival rate in these conditions is extremely low. For more than a decade gemcitabine has been the cornerstone of metastatic PDAC treatment, although survival benefit was very poor. PDAC cells are surrounded by an intense desmoplastic reaction that may create a barrier to the drugs penetration within the tumor. Recently PDAC stroma has been addressed as a potential therapeutic target. Nano albumin bound (Nab)-paclitaxel is an innovative molecule depleting tumor stroma, through interaction between albumin and secreted protein acidic and rich in cysteine. Addition of nab-paclitaxel to gemcitabine has showed activity and efficacy in metastatic PDAC first-line treatment improving survival and overall response rate gemcitabine alone in the MPACT phase III study. This combination represents one of the standards of care in advanced PDAC therapy and is suitable to a broader spectrum of patients compared to other schedules. Nab-paclitaxel is under investigation as a backbone of chemotherapy in novel combinations with target agents or immunotherapy in locally advanced or metastatic PDAC. In this article, we provide an updated and critical overview about the role of nab-paclitaxel in PDAC treatment based on the latest advances in preclinical and clinical research. Furthermore, we focus on the use of nab-paclitaxel within the context of metastatic PDAC treatment landscape and we discuss about future implications in the light of current clinical ongoing trials.
胰腺癌(PDAC)是一种侵袭性和化疗耐药性疾病,是西方国家癌症相关死亡的第四大原因。大多数患者在诊断时已患有不可切除的局部晚期或转移性疾病,这些情况下的 5 年生存率极低。十多年来,吉西他滨一直是转移性 PDAC 治疗的基石,尽管生存获益非常有限。PDAC 细胞被强烈的促结缔组织增生反应所包围,这可能会在药物渗透到肿瘤内部时形成障碍。最近,PDAC 基质已被视为潜在的治疗靶点。纳米白蛋白结合(nab)紫杉醇是一种创新的分子,通过白蛋白与分泌蛋白酸和富含半胱氨酸的相互作用来消耗肿瘤基质。在转移性 PDAC 的一线治疗中,与吉西他滨联合使用 nab-紫杉醇在 MPACT 三期研究中显示出了活性和疗效,提高了生存率和总缓解率,优于单独使用吉西他滨。在晚期 PDAC 治疗中,该联合方案是一种标准治疗方案,与其他方案相比,适用于更广泛的患者群体。nab-紫杉醇正在与局部晚期或转移性 PDAC 的靶向药物或免疫疗法进行新型联合化疗的研究。在本文中,我们根据临床前和临床研究的最新进展,对 nab-紫杉醇在 PDAC 治疗中的作用进行了更新和批判性的综述。此外,我们还重点讨论了在转移性 PDAC 治疗领域中使用 nab-紫杉醇的情况,并根据当前正在进行的临床试验讨论了未来的影响。