H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, USA.
Oncologist. 2021 Feb;26(2):115-119. doi: 10.1002/onco.13611. Epub 2020 Dec 8.
5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) has activity in pancreatic neuroendocrine tumors (pNETs), but its use is limited, partly because of toxicities. pNETs can often become aggressive over time. We evaluated the efficacy of FOLFOX in patients with aggressive pNETs who had progressed after capecitabine plus temozolomide (cap/tem) among other treatments.
This was a retrospective study of all patients with well-differentiated metastatic pNETs, treated at an academic cancer center between January 2008 and June 2019, who received FOLFOX and had received cap/tem in the past. The primary endpoint was objective response rate.
Thirty-one patients met eligibility criteria. Twenty-five received FOLFOX, and six received FOLFOX with bevacizumab. Patients were heavily pretreated, having received a median of three prior lines of systemic therapy prior to FOLFOX (range, 1-8). Three (9.7%) patients had grade [G]1 tumors, 16 (51.6%) had G2, and 6 (19.4%) had G3, and grade was unspecified in 6 (19.4%) patients. Fourteen (45.2%) exhibited a best response of partial radiographic response per RECIST 1.1 criteria, 15 (48.4%) stable disease, and 2 (6.4%) progressive disease; overall response rate was 45.2% and disease control rate was 93.5%. Median progression-free survival was 6 months (95% confidence interval [CI], 5.0-7.0), and median overall survival was 16 months from onset of study treatment (95% CI, 11.3-20.7) and 67 months from date of diagnosis (95% CI, 49.8-84.2). Median duration of treatment was 3 months, and median duration of response was 2 months. Toxicity profile was consistent with known adverse events associated with this regimen.
FOLFOX is active in aggressive, heavily pretreated pNETs that have progressed on prior cap/tem chemotherapy; response durations are relatively short.
FOLFOX chemotherapy has robust activity in patients with rapidly progressive, heavily pretreated pancreatic neuroendocrine tumors (NETs), a setting in which few, if any, other options are likely to be effective. Durations of response, however, are relatively short, and new treatments are urgently needed for patients with aggressive transformation of pancreatic NETs.
5-氟尿嘧啶、亚叶酸钙和奥沙利铂（FOLFOX）在胰腺神经内分泌肿瘤（pNETs）中有活性，但由于毒性，其应用受到限制。pNETs 随着时间的推移往往会变得更具侵袭性。我们评估了在接受卡培他滨联合替莫唑胺（cap/tem）等治疗后进展的侵袭性 pNETs 患者中使用 FOLFOX 的疗效。
这是一项回顾性研究，纳入了 2008 年 1 月至 2019 年 6 月期间在一家学术癌症中心接受治疗的所有分化良好的转移性 pNETs 患者，这些患者接受了 FOLFOX 治疗，且在过去曾接受过 cap/tem 治疗。主要终点是客观缓解率。
31 名患者符合入选标准。25 名患者接受了 FOLFOX 治疗，6 名患者接受了 FOLFOX 联合贝伐珠单抗治疗。患者接受了大量的预处理，在接受 FOLFOX 治疗之前，中位数接受了三线全身治疗（范围为 1-8 线）。3 名（9.7%）患者的肿瘤为 G1 级，16 名（51.6%）为 G2 级，6 名（19.4%）为 G3 级，6 名（19.4%）患者的肿瘤分级未明确。14 名（45.2%）患者按 RECIST 1.1 标准表现出部分放射学缓解，15 名（48.4%）患者疾病稳定，2 名（6.4%）患者疾病进展；总体缓解率为 45.2%，疾病控制率为 93.5%。无进展生存期的中位数为 6 个月（95%置信区间[CI]，5.0-7.0），总生存期的中位数为从研究治疗开始的 16 个月（95%CI，11.3-20.7）和从诊断日期的 67 个月（95%CI，49.8-84.2）。中位治疗持续时间为 3 个月，中位缓解持续时间为 2 个月。毒性谱与该方案相关的已知不良事件一致。
FOLFOX 在先前接受 cap/tem 化疗后进展的侵袭性、预处理过多的 pNETs 中具有活性；缓解持续时间相对较短。
FOLFOX 化疗在进展迅速、预处理过多的胰腺神经内分泌肿瘤（NETs）患者中具有较强的活性，在这些患者中，可能很少有（如果有的话）其他有效的治疗选择。然而，缓解持续时间相对较短，对于发生侵袭性转化的胰腺 NETs 患者，迫切需要新的治疗方法。
