Isacoff William H, Cooper Brandon, Bartlett Andrew, McCarthy Brian, Yu Kenneth H
Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA 90095, USA.
Adera Biolabs, Germantown, MD 20876, USA.
Cancers (Basel). 2022 Jun 13;14(12):2906. doi: 10.3390/cancers14122906.
Cytotoxic chemotherapy remains the mainstay of treatment for advanced pancreatic adenocarcinoma (PDAC). Emerging studies support metronomic chemotherapy (MCT) as effective, challenging established paradigms of dosing and schedules. The blood-based ChemoSensitivity Assay has been shown to predict response and survival in advanced PDAC patients treated with standard chemotherapy. The current study combines these concepts for a highly personalized treatment approach. This was a retrospective analysis; a pilot ( = 50) and validation cohort ( = 45) were studied. The ChemoSensitivity Assay was performed at baseline and during therapy; results were correlated to drugs administered and patient outcomes. MCT was administered based on the assay results at the treating physician's discretion. Patients in the pilot cohort experienced favorable survival compared with historical controls (median overall survival (mOS) 16.8 mo). Patients whose treatment closely matched the ChemoSensitivity Assay predictions experienced longer median time on lines of therapy (5.3 vs. 3.3 mo, = 0.02) and showed a trend for longer mOS (20.9 vs. 12.5 mo, = 0.055) compared with those not closely matched. These findings were confirmed in the validation cohort. Overall, patients treated with MCT closely matching Assay results experienced a remarkable mOS of 27.7 mo. ChemoSensitivity profiling-guided MCT is a promising approach for personalized therapy in advanced PDAC.
细胞毒性化疗仍然是晚期胰腺腺癌（PDAC）治疗的主要手段。新出现的研究支持节拍化疗（MCT）是有效的，这对既定的给药剂量和方案范式提出了挑战。基于血液的化疗敏感性检测已被证明可预测接受标准化疗的晚期PDAC患者的反应和生存情况。本研究将这些概念结合起来，形成一种高度个性化的治疗方法。这是一项回顾性分析；研究了一个试点队列（n = 50）和一个验证队列（n = 45）。在基线和治疗期间进行化疗敏感性检测；结果与所给予的药物和患者预后相关。根据检测结果，由主治医生酌情给予MCT。与历史对照相比，试点队列中的患者生存期良好（中位总生存期[mOS]为16.8个月）。与那些治疗方案与化疗敏感性检测预测结果不太匹配的患者相比，治疗方案与检测预测结果紧密匹配的患者中位治疗线时间更长（5.3个月对3.3个月，P = 0.02），且mOS有延长趋势（20.9个月对12.5个月，P = 0.055）。这些发现在验证队列中得到了证实。总体而言，接受MCT且治疗方案与检测结果紧密匹配的患者mOS达到了显著的27.7个月。化疗敏感性分析指导下的MCT是晚期PDAC个性化治疗的一种有前景的方法。
