Ramanathan Ramesh K, Weiss Glen J, Posner Richard G, Rajeshkumar N V, Jameson Gayle, Aziz Meraj, Hoering Antje, Bolejack Vanessa, Maitra Anirban, Fulk Monica, Stites Edward C, Hlavacek William S, Gatalica Zoran, Xiu Joanne, Hidalgo Manuel, Von Hoff Daniel D, Barrett Michael T
Honor Health Research Institute, Scottsdale, AZ, USA.
Mayo Clinic Cancer Center, Phoenix, AZ, USA.
J Gastrointest Oncol. 2017 Dec;8(6):925-935. doi: 10.21037/jgo.2017.09.05.
The choice of a regimen in metastatic pancreatic cancer patients following progression on 1st line therapy is empiric and outcomes are unsatisfactory. This phase II study was performed to evaluate the efficacy of therapy selected by immunohistochemistry (IHC) in these patients following progression after one or more therapies.
Eligible patients underwent a percutaneous biopsy of a metastatic lesion and treatment selection was determined by IHC. The study required 35 evaluable patients (power of 86%) for detecting a true 1-year survival rate of >20%.
A tumor biopsy was performed in 48 of 49 accrued patients. Study therapy was not given (n=13) either due to insufficient tumor on biopsy (n=8) or due to worsening cancer related symptoms after biopsy (n=5). The demographics of evaluable patients (n=35) are male/female (59%/41%), with age range 34-78 years (median 63 years). Patients had 1-6 prior regimens (median of 2). The most common IHC targets were topoisomerase 1 or 2, thymidylate synthase, excision repair cross-complementation group 1 protein (ERCC1), and osteonectin secreted protein acidic and rich in cysteine (SPARC). Commercially available treatment regimens prescribed included FOLFIRI, FOLFOX, irinotecan, and doxorubicin. The response (RECIST) was 9%, the median survival was 5.6 months (94% CI, 3.8-8.2), and the 1-year survival was 20% (95% CI, 7-33%).
In all patients, IHC assays resulted in identification of at least two targets for therapy and a non-cross resistant regimen could be prescribed for therapy with evidence of some benefit. An IHC based treatment strategy is feasible and needs validation in larger studies.
一线治疗进展后的转移性胰腺癌患者的治疗方案选择是经验性的，且治疗效果不尽人意。本II期研究旨在评估在接受一种或多种治疗进展后，通过免疫组织化学（IHC）选择的治疗方案对这些患者的疗效。
符合条件的患者接受转移性病灶的经皮活检，并通过IHC确定治疗方案。该研究需要35例可评估患者（检验效能为86%）以检测真实的1年生存率>20%。
49例入组患者中的48例进行了肿瘤活检。由于活检时肿瘤不足（n=8）或活检后癌症相关症状恶化（n=5），13例患者未接受研究治疗。可评估患者（n=35）的人口统计学特征为男性/女性（59%/41%），年龄范围为34 - 78岁（中位数63岁）。患者之前接受过1 - 6种治疗方案（中位数为2种）。最常见的IHC靶点是拓扑异构酶1或2、胸苷酸合成酶、切除修复交叉互补组1蛋白（ERCC1）以及富含半胱氨酸的酸性分泌蛋白（SPARC）。所开具的市售治疗方案包括FOLFIRI、FOLFOX、伊立替康和多柔比星。缓解率（根据实体瘤疗效评价标准）为9%，中位生存期为5.6个月（94%置信区间，3.8 - 8.2），1年生存率为20%（95%置信区间，7 - 33%）。
在所有患者中，IHC检测可确定至少两个治疗靶点，并且可以开具一种无交叉耐药的治疗方案，且有一定获益证据。基于IHC的治疗策略是可行的，需要在更大规模的研究中进行验证。
