Nagata Naoki, Mishima Hideyuki, Kurosawa Shuichi, Oba Koji, Sakamoto Junichi
Kitakyushu General Hospital, Kitakyushu, Japan.
Aichi Medical University, Nagakute, Japan.
Clin Colorectal Cancer. 2017 Jun;16(2):154-157.e1. doi: 10.1016/j.clcc.2017.02.001. Epub 2017 Mar 1.
In Japan, oxaliplatin (OXA)/5-fluorouracil (5-FU)/leucovorin (LV)-the mFOLFOX6 regimen-is the most frequently used first-line chemotherapy backbone for metastatic colorectal cancer. However, peripheral nerve disorders caused by OXA during mFOLFOX6 therapy can decrease patients' quality of life. OXA can be safely discontinued from a FOLFOX regimen after 6 cycles during first-line therapy. Also, for patients who discontinue OXA without having experienced peripheral nerve disorders, reintroducing OXA in the later stages of treatment could remain an option.
The study is a phase II, multicenter, open-label, parallel-group, randomized, controlled exploratory study comparing the efficacy and safety of mFOLFOX6 plus panitumumab and 5-FU/LV plus panitumumab in patients with chemotherapy-naïve, unresectable, advanced or recurrent colorectal carcinoma of RAS wild-type (SAPPHIRE; ClinicalTrials.gov identifier, NCT02337946). Eligible patients will receive 6 cycles of mFOLFOX6 plus panitumumab combination therapy, followed by 1:1 randomization to either further treatment with mFOLFOX6 plus panitumumab or discontinuation of OXA and treatment with 5-FU/LV plus panitumumab. Up to 100 randomized patients will receive treatment for approximately 12 months or until any of the criteria for treatment discontinuation have been met. The primary endpoint is progression-free survival rate at 9 months after the day of randomization. The secondary endpoints are progression-free survival, overall survival, response rate, and interval to treatment failure. Safety will be evaluated according to the incidence and severity of adverse events, including the incidence of peripheral nerve and skin disorders. Additional endpoints will include maintenance of performance status, continuation of OXA in the mFOLFOX6 plus panitumumab group, and continuation of panitumumab in both groups.
在日本，奥沙利铂（OXA）/5-氟尿嘧啶（5-FU）/亚叶酸钙（LV）——即mFOLFOX6方案——是转移性结直肠癌最常用的一线化疗基础方案。然而，mFOLFOX6治疗期间奥沙利铂引起的周围神经病变会降低患者的生活质量。在一线治疗中，奥沙利铂在6个周期后可安全地从FOLFOX方案中停用。此外，对于未出现周围神经病变而停用奥沙利铂的患者，在治疗后期重新引入奥沙利铂仍是一种选择。
本研究是一项II期、多中心、开放标签、平行组、随机、对照探索性研究，比较mFOLFOX6联合帕尼单抗与5-FU/LV联合帕尼单抗在RAS野生型、未经化疗、不可切除的晚期或复发性结直肠癌患者中的疗效和安全性（蓝宝石研究；ClinicalTrials.gov标识符，NCT02337946）。符合条件的患者将接受6个周期的mFOLFOX6联合帕尼单抗联合治疗，随后按1:1随机分组，分别接受mFOLFOX6联合帕尼单抗进一步治疗或停用奥沙利铂并接受5-FU/LV联合帕尼单抗治疗。最多100名随机分组患者将接受约12个月的治疗，或直至满足任何治疗中止标准。主要终点是随机分组后9个月的无进展生存率。次要终点是无进展生存期、总生存期、缓解率和至治疗失败时间。将根据不良事件的发生率和严重程度评估安全性，包括周围神经和皮肤疾病的发生率。其他终点将包括体能状态的维持、mFOLFOX6联合帕尼单抗组中奥沙利铂的持续使用以及两组中帕尼单抗的持续使用。
