Centro Integral Oncológico Clara Campal, Oña 10, 28050 Madrid, Spain.
Br J Cancer. 2013 Aug 20;109(4):926-33. doi: 10.1038/bjc.2013.415. Epub 2013 Aug 1.
Nab-paclitaxel and gemcitabine have demonstrated a survival benefit over gemcitabine alone in advanced pancreatic cancer (PDA). This study aimed to investigate the clinical, biological, and imaging effects of the regimen in patients with operable PDA.
Patients with operable PDA received two cycles of nab-paclitaxel and gemcitabine before surgical resection. FDG-PET and CA19.9 tumour marker levels were used to measure clinical activity. Effects on tumour stroma were determined by endoscopic ultrasound (EUS) elastography. The collagen content and architecture as well as density of cancer-associated fibroblasts (CAFs) were determined in the resected surgical specimen and compared with a group of untreated and treated with conventional chemoradiation therapy controls. A co-clinical study in a mouse model of PDA was conducted to differentiate between the effects of nab-paclitaxel and gemcitabine.
A total of 16 patients were enrolled. Treatment resulted in significant antitumour effects with 50% of patients achieving a >75% decrease in circulating CA19.9 tumour marker and a response by FDG-PET. There was also a significant decrement in tumour stiffness as measured by EUS elastography. Seven of 12 patients who completed treatment and were operated had major pathological regressions. Analysis of residual tumours showed a marked disorganised collagen with a very low density of CAF, which was not observed in the untreated or conventionally treated control groups. The preclinical co-clinical study showed that these effects were specific of nab-paclitaxel and not gemcitabine.
These data suggest that nab-paclitaxel and gemcitabine decreases CAF content inducing a marked alteration in cancer stroma that results in tumour softening. This regimen should be studied in patients with operable PDA.
纳布紫杉醇和吉西他滨在晚期胰腺癌（PDA）中已显示出比吉西他滨单药治疗更具生存优势。本研究旨在研究该方案在可手术 PDA 患者中的临床、生物学和影像学效果。
可手术的 PDA 患者在手术切除前接受两周期纳布紫杉醇和吉西他滨治疗。使用 FDG-PET 和 CA19.9 肿瘤标志物水平来衡量临床疗效。通过内镜超声（EUS）弹性成像来确定肿瘤基质的影响。在切除的手术标本中测定胶原含量和结构以及癌相关成纤维细胞（CAF）的密度，并与一组未经治疗和接受常规放化疗的对照组进行比较。在 PDA 小鼠模型中进行了一项合作临床研究，以区分纳布紫杉醇和吉西他滨的作用。
共纳入 16 例患者。治疗后肿瘤有明显的抗肿瘤作用，50%的患者循环 CA19.9 肿瘤标志物下降>75%，FDG-PET 有反应。EUS 弹性成像也显示肿瘤硬度显著降低。12 例完成治疗并接受手术的患者中有 7 例发生主要病理缓解。对残留肿瘤的分析显示，胶原排列紊乱，CAF 密度极低，这在未经治疗或常规治疗对照组中未观察到。临床前合作研究表明，这些作用是纳布紫杉醇特有的，而不是吉西他滨的作用。
这些数据表明，纳布紫杉醇和吉西他滨可降低 CAF 含量，导致肿瘤基质发生明显改变，从而使肿瘤变软。该方案应在可手术的 PDA 患者中进行研究。
