Department of Engineering for Innovation Medicine, Section of Oncology, University and Hospital Trust of Verona, Verona, Italy.
Department of Interdisciplinary Medicine, University of Bari Aldo Moro, Bari, Italy.
J Natl Compr Canc Netw. 2024 May 14;22(5):e247005. doi: 10.6004/jnccn.2024.7005.
High-grade neuroendocrine neoplasms (NENs) comprise both well-differentiated grade 3 neuroendocrine tumors (G3 NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) nearly always include poorly differentiated NEC as the neuroendocrine component. The efficacy and safety of frontline mFOLFIRINOX chemotherapy has never been investigated in patients with high-grade NENs.
We conducted a multi-institutional retrospective analysis of patients with advanced high-grade NEN of the gastroenteropancreatic tract or of unknown origin seen between February 2016 and April 2023 who received treatment with frontline mFOLFIRINOX.
A total of 35 patients were included (G3 NETs: n=2; NECs: n=25; MiNENs: n=8; stage III: n=5; stage IV: n=30). The objective response rate was 77% (complete response: 3%; partial response: 74%). Median progression-free survival was 12 months (95% CI, 9.2-16.2 months) and median overall survival was 20.6 months (95% CI, 17.2-30.6 months). No significant differences in efficacy were seen according to primary site, histopathology, and Ki-67 proliferative index. All 5 patients with stage III disease who received mFOLFIRINOX obtained an objective response and underwent radical surgery or definitive radiotherapy with curative intent, with a recurrence rate of 40%. Grade 3 or 4 adverse events were observed in 43% of patients (mainly neutropenia and diarrhea). Females were at significantly increased risk of developing severe toxicities.
mFOLFIRINOX shows antitumor activity against high-grade NENs. Well-designed, prospective clinical trials are needed to assess the efficacy of mFOLFIRINOX in both the neoadjuvant and metastatic settings.
高级别神经内分泌肿瘤（NENs）包括分化良好的 3 级神经内分泌肿瘤（G3 NETs）和分化差的神经内分泌癌（NECs）。混合性神经内分泌-非神经内分泌肿瘤（MiNENs）几乎总是包含分化差的 NEC 作为神经内分泌成分。一线 mFOLFIRINOX 化疗在高级别 NEN 患者中的疗效和安全性尚未得到研究。
我们对 2016 年 2 月至 2023 年 4 月期间接受一线 mFOLFIRINOX 治疗的晚期胃肠胰或来源不明的高级别 NEN 患者进行了多机构回顾性分析。
共纳入 35 例患者（G3 NETs：n=2；NECs：n=25；MiNENs：n=8；III 期：n=5；IV 期：n=30）。客观缓解率为 77%（完全缓解：3%；部分缓解：74%）。中位无进展生存期为 12 个月（95%CI，9.2-16.2 个月），中位总生存期为 20.6 个月（95%CI，17.2-30.6 个月）。根据原发部位、组织病理学和 Ki-67 增殖指数，疗效无显著差异。所有 5 例 III 期患者接受 mFOLFIRINOX 治疗后均获得客观缓解，并接受根治性手术或明确的有治愈意图的放疗，复发率为 40%。43%的患者出现 3 级或 4 级不良事件（主要为中性粒细胞减少和腹泻）。女性发生严重毒性的风险显著增加。
mFOLFIRINOX 对高级别 NEN 具有抗肿瘤活性。需要进行精心设计的前瞻性临床试验，以评估 mFOLFIRINOX 在新辅助和转移性环境中的疗效。
