Brzezniak Christina, Schmitz Bruno A, Peterson Paul G, Degesys Aiste, Oronsky Bryan T, Scicinski Jan J, Caroen Scott Z, Carter Corey A
Walter Reed National Military Medical Center, Bethesda, Md., USA.
EpicentRx, Inc., Mountain View, Calif., USA.
Case Rep Oncol. 2016 Jan 15;9(1):45-50. doi: 10.1159/000443605. eCollection 2016 Jan-Apr.
We present the case of a 49-year-old male with metastatic epidermal growth factor receptor (EGFR) mutation-positive adenocarcinoma of the lung that continues to outlive stage IV diagnosis of non-small cell lung cancer after treatment with RRx-001, an experimental anticancer agent with epigenetic and immunologic activity, in the context of a phase II clinical trial called TRIPLE THREAT. Currently, no adequate treatment options exist for patients with EGFR mutation-positive tumors who have failed a 1st-generation tyrosine kinase inhibitor (erlotinib or gefitinib) treatment and do not develop a resistant mutation. Biopsy of a large pancreatic metastasis after RRx-001 demonstrated extensive necrosis with CD3+ and CD8+ immune cell infiltration that appears to correlate with prolonged survival despite end-stage disease. These results suggest that the mode of action of RRx-001 is related to immune stimulation in addition to epigenetic inhibition.
我们报告了一例49岁男性转移性表皮生长因子受体（EGFR）突变阳性肺腺癌患者的病例。在一项名为“TRIPLE THREAT”的II期临床试验中，该患者接受了具有表观遗传和免疫活性的实验性抗癌药物RRx-001治疗，在IV期非小细胞肺癌诊断后仍存活至今。目前，对于第一代酪氨酸激酶抑制剂（厄洛替尼或吉非替尼）治疗失败且未发生耐药突变的EGFR突变阳性肿瘤患者，尚无足够的治疗选择。RRx-001治疗后对一个大的胰腺转移灶进行活检，显示广泛坏死，伴有CD3+和CD8+免疫细胞浸润，尽管处于终末期疾病，但这似乎与生存期延长相关。这些结果表明，RRx-001的作用方式除了表观遗传抑制外，还与免疫刺激有关。
