Department of Medicine, David Geffen School of Medicine at University of California Los Angeles (UCLA), 1301 20th Street, Suite 280, Santa Monica, CA, 90404, USA.
Department of Surgery, Division of General Surgery, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, USA.
Target Oncol. 2018 Aug;13(4):461-468. doi: 10.1007/s11523-018-0572-3.
Continuous-infusion 5-fluorouracil (5FU) and calcium leucovorin plus nab-paclitaxel and oxaliplatin have been shown to be active in patients with pancreatic cancer. As a protracted low-dose infusion, 5FU is antiangiogenic, and has synergy with bevacizumab. As shown in the treatment of breast cancer, bevacizumab and nab-paclitaxel are also synergetic.
In this paper we retrospectively analyze the survival of 65 patients with advanced pancreatic cancer who were treated with low-dose continuous (metronomic) chemotherapy given in conjunction with conventional anti-VEGF therapy.
Since July of 2008, we have treated 65 patients with 5FU (180 mg/m/day × 14 days) via an ambulatory pump. Calcium leucovorin (20 mg/m IV), nab-paclitaxel (60 mg/m) IV as a 30-min infusion, and oxaliplatin (50 mg/m) IV as a 60-min infusion were given on days 1, 8, and 15. Bevacizumab (5 mg/kg) IV over 30 min was administered on days 1 and 15. Cycles were repeated every 28-35 days. There were 42 women and 23 men, and the median age was 59 years. Forty-six patients had stage IV disease.
The median survival was 19 months, with 82% of patients surviving 12 months or longer. The overall response rate was 49%. There were 28 patients who had received prior treatment, 15 of whom responded to therapy. Fifty-two patients had elevated CA 19-9 prior to treatment. Of these, 21 patients had 90% or greater reduction in CA 19-9 levels. This cohort had an objective response rate of 71% and a median survival of 27 months. Thirty patients stopped treatment due to disease progression, and an additional 22 stopped because of toxicity. One patient died while on therapy.
This non-gemcitabine-based regimen resulted in higher response rates and better survival than what is commonly observed with therapy given at conventional dosing schedules. Low-dose continuous (metronomic therapy) cytotoxic chemotherapy combined with antiangiogenic therapy is safe and effective.
持续输注氟尿嘧啶（5FU）和亚叶酸钙加 nab-紫杉醇和奥沙利铂已被证明对胰腺癌患者有效。作为一种延长的低剂量输注，5FU 具有抗血管生成作用，并与贝伐珠单抗具有协同作用。如在乳腺癌治疗中所示，贝伐珠单抗和 nab-紫杉醇也具有协同作用。
在本文中，我们回顾性分析了 65 例晚期胰腺癌患者的生存情况，这些患者接受了低剂量连续（节拍）化疗联合常规抗 VEGF 治疗。
自 2008 年 7 月以来，我们通过便携式泵为 65 例患者输注 5FU（180mg/m/天×14 天）。亚叶酸钙（20mg/m 静脉注射）、nab-紫杉醇（60mg/m）静脉注射 30 分钟，奥沙利铂（50mg/m）静脉注射 60 分钟，均在第 1、8 和 15 天给予。贝伐珠单抗（5mg/kg）静脉输注 30 分钟，在第 1 和第 15 天给予。每 28-35 天重复一个周期。其中女性 42 例，男性 23 例，中位年龄 59 岁。46 例患者为 IV 期疾病。
中位生存时间为 19 个月，82%的患者存活 12 个月或更长时间。总体缓解率为 49%。有 28 例患者之前接受过治疗，其中 15 例对治疗有反应。52 例患者在治疗前 CA19-9 升高。其中，21 例患者的 CA19-9 水平降低 90%或更多。该队列的客观缓解率为 71%，中位生存时间为 27 个月。30 例患者因疾病进展停止治疗，另有 22 例因毒性停止治疗。1 例患者在治疗期间死亡。
与常规剂量方案治疗相比，这种非吉西他滨为基础的方案导致更高的缓解率和更好的生存。低剂量连续（节拍治疗）细胞毒化疗联合抗血管生成治疗是安全有效的。
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