Pharmacy Clinical Programs, U.T. M.D. Anderson Cancer Center, Houston, Texas, USA.
Department of Biostatistics, U.T. M.D. Anderson Cancer Center, Houston, Texas, USA.
Oncology. 2020;98(5):289-294. doi: 10.1159/000505974. Epub 2020 Feb 25.
Advanced unresectable gastroesophageal cancers continue to confer a dismal patient prognosis. Limited options remain once the cancer is refractory to cytotoxics/biologics (like irinotecan, taxane, and ramucirumab). Recently, anti-programmed death-1 (anti-PD-1) inhibitors have been used with limited efficacy in select patients with adenocarcinoma. Similarly, irinotecan-based therapy has marginal efficacy. We combined irinotecan plus a fluoropyrimidine with an anti-PD-1 antibody, nivolumab, with hopes of having a higher advantage for patients.
Primary objective was to assess safety judged by toxicities, dose delays, or dose reductions. Secondary endpoints included the assessment of response, overall survival (OS), and progression-free survival (PFS).
We treated 15 patients with this combination during July 2017 to April 2019. Patients were included if they had follow-up at our institution.
Median doses given were nivolumab 240 mg + irinotecan 120 mg/m2 + 5-FU 2,000 mg/m2 over 46-48 h (or capecitabine 1,250 mg/m2/day; 7 days on, 7 days off) given every 2 weeks. Median age of the patients was 55 years, and all patients had an ECOG performance status of 0-1. The patients had a median of 1 prior therapy. Slightly over half of the patients had PD-L1 expression. The median number of cycles was 7. Five patients (33%) had a dose delay or dose adjustment. The most common reason for dose delay or adjustment was grade 2 fatigue. Disease control (response or stability) on first scan was 73.3% (n = 11). Median PFS and OS for the entire group was 7 and 13.3 months, respectively.
In this small cohort of patients, we conclude that this combination is quite feasible and resulted in prolonged stability in some patients. Further development of this regimen is warranted.
晚期不可切除的胃食管腺癌患者预后仍然较差。一旦癌症对细胞毒药物/生物制剂（如伊立替康、紫杉烷和雷莫芦单抗）产生耐药性，治疗选择非常有限。最近，抗程序性死亡-1（抗 PD-1）抑制剂已在少数腺癌患者中显示出一定的疗效。同样，伊立替康为基础的治疗也仅有轻微疗效。我们联合伊立替康和氟嘧啶类药物与抗 PD-1 抗体纳武利尤单抗，希望能为患者带来更高的优势。
主要目的是评估毒性、剂量延迟或剂量减少判断的安全性。次要终点包括反应评估、总生存期（OS）和无进展生存期（PFS）。
我们在 2017 年 7 月至 2019 年 4 月期间用该联合方案治疗了 15 例患者。如果患者在我们机构有随访，就可以纳入本研究。
中位给予的剂量为：nivolumab 240mg+irinotecan 120mg/m2+5-FU 2000mg/m2 持续 46-48 小时（或卡培他滨 1250mg/m2/天；7 天给药，7 天停药），每 2 周一次。患者的中位年龄为 55 岁，所有患者的 ECOG 体能状态为 0-1。患者的中位治疗线数为 1 线。略超过一半的患者有 PD-L1 表达。中位治疗周期数为 7 个。5 例（33%）患者出现剂量延迟或剂量调整。剂量延迟或调整的最常见原因是 2 级疲劳。首次扫描的疾病控制（反应或稳定）率为 73.3%（n=11）。整个队列的中位 PFS 和 OS 分别为 7 个月和 13.3 个月。
在这个小患者队列中，我们的结论是，这种联合方案非常可行，并使一些患者的病情稳定时间延长。需要进一步开发这种方案。
