Department of Gastrointestinal Medical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital (Fujian Branch of Fudan University Shanghai Cancer Center), Fuzhou, China.
Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou, China.
Cancer Sci. 2024 May;115(5):1611-1621. doi: 10.1111/cas.16110. Epub 2024 Feb 14.
Chinese guidelines recommend POF (paclitaxel, oxaliplatin, and 5-FU/levoleucovorin) as first-line treatment for advanced gastric cancer (AGC). Apatinib can augment the antitumor effect of paclitaxel, oxaliplatin, or fluorouracil in preclinical studies of AGC. A phase I clinical trial was conducted to evaluate the anticancer activity and maximum tolerated dose (MTD) of apatinib plus POF in treatment-naïve patients with AGC and to establish a recommended phase II dose. Participants received escalating doses of daily oral apatinib (250, 375, 500, 625, 750, and 850 mg) plus POF every 2 weeks using a conventional "3 + 3" study design. Among 21 treated patients, one experienced a dose-limiting toxicity (grade 3 skin ulceration at 850 mg). No MTD was reached. Apatinib 750 mg plus POF was recommended for phase II study. The most common grade 3-4 adverse events (AEs) were neutropenia (33.3%), mucositis (14.3%), and hand-foot syndrome (14.3%). Median progression-free and overall survival were 10.4 months (95% CI: 6.3, 14.6) and 18.4 months (95% CI: 9.8, 28.2), respectively. Apatinib up to 850 mg coadministered with POF was well tolerated with manageable AEs. The safety and anticancer activity of this regimen warrants its further investigation as first-line treatment for AGC in a larger study.
中国指南推荐 POF（紫杉醇、奥沙利铂和 5-FU/左亚叶酸）作为晚期胃癌（AGC）的一线治疗方案。在 AGC 的临床前研究中，阿帕替尼可以增强紫杉醇、奥沙利铂或氟尿嘧啶的抗肿瘤作用。一项 I 期临床试验旨在评估阿帕替尼联合 POF 治疗初治 AGC 患者的抗癌活性和最大耐受剂量（MTD），并确定推荐的 II 期剂量。参与者接受每日口服阿帕替尼（250、375、500、625、750 和 850mg）递增剂量联合 POF 每 2 周一次，采用常规的“3+3”研究设计。在 21 名接受治疗的患者中，1 名患者发生剂量限制毒性（850mg 时 3 级皮肤溃疡）。未达到 MTD。推荐阿帕替尼 750mg 联合 POF 进行 II 期研究。最常见的 3-4 级不良事件（AE）为中性粒细胞减少症（33.3%）、黏膜炎（14.3%）和手足综合征（14.3%）。中位无进展生存期和总生存期分别为 10.4 个月（95%CI：6.3，14.6）和 18.4 个月（95%CI：9.8，28.2）。阿帕替尼联合 POF 剂量高达 850mg 耐受性良好，AE 可管理。该方案的安全性和抗癌活性值得进一步研究，以作为更大规模研究中 AGC 的一线治疗方案。
