Department of Gastroenterology, Gifu Municipal Hospital, Japan 7-1 Kashimacho, Gifu City, 500-8513, Japan.
Department of Gastroenterology, Matsunami General Hospital, Kanazawa, Japan.
Med Oncol. 2024 Jul 5;41(8):195. doi: 10.1007/s12032-024-02438-x.
Gemcitabine plus nab-paclitaxel (GnP) and FOLFIRINOX are widely used as first-line regimens for unresectable pancreatic cancer (PC). When GnP therapy is selected, considering patient age or condition, second-line FOLFIRINOX is sometimes difficult to administer owing to its toxicity. This study aimed to determine the recommended dose (RD) of S-IROX (S-1, oxaliplatin, and irinotecan combination) regimens in patients with unresectable PC after first-line GnP failure. This phase-I study used the "3 + 3" dose-escalation design with two dose levels. Patients who failed first-line GnP therapy for unresectable PC were enrolled. Oxaliplatin and irinotecan were administered on day 1, and S-1 was administered orally twice daily on days 1-7, followed by 7 days of rest. The primary endpoints were dose-limiting toxicities (DLTs) and determination of RD. The secondary endpoint was the evaluation of potential antitumor activity. Nine patients received the second-line S-IROX regimen. In level-0 (S-1, 80 mg/m; oxaliplatin, 85 mg/m; and irinotecan, 120 mg/m), no patient experienced DLT; however, one patient experienced grade 3 neutropenia. At level-1 (irinotecan increased to 150 mg/m), one of six patients experienced DLTs, including G3 diarrhea. The RD was confirmed at the level-1 dose. The response rate, disease control rate, median progression-free survival, and median overall survival were 33.3%, 77.8%, 172 (range:77-422) days, and 414 (101-685) days, respectively. One patient underwent surgery after the second-line S-IROX therapy. Second-line S-IROX treatment was deemed acceptable. The RD was set at level-1 dose (S-1, 80 mg/m; oxaliplatin, 85 mg/m; and irinotecan, 150 mg/m).
吉西他滨联合 nab-紫杉醇（GnP）和 FOLFIRINOX 广泛用于不可切除的胰腺癌（PC）的一线治疗方案。当选择 GnP 治疗时，由于其毒性，考虑到患者的年龄或身体状况，二线 FOLFIRINOX 有时难以给药。本研究旨在确定不可切除 PC 一线 GnP 治疗失败后二线 S-IROX（S-1、奥沙利铂和伊立替康联合）方案的推荐剂量（RD）。这项 I 期研究采用了“3+3”剂量递增设计，有两个剂量水平。入组患者为不可切除 PC 一线 GnP 治疗失败的患者。奥沙利铂和伊立替康于第 1 天给药，S-1 于第 1-7 天每天口服 2 次，随后休息 7 天。主要终点是剂量限制性毒性（DLT）和确定 RD。次要终点是评估潜在的抗肿瘤活性。9 名患者接受了二线 S-IROX 治疗方案。在 0 级（S-1，80mg/m；奥沙利铂，85mg/m；伊立替康，120mg/m），无患者发生 DLT；然而，1 名患者发生 3 级中性粒细胞减少症。在 1 级（伊立替康增加至 150mg/m），6 名患者中有 1 名发生 DLT，包括 G3 腹泻。在 1 级剂量下确认了 RD。客观缓解率、疾病控制率、中位无进展生存期和中位总生存期分别为 33.3%、77.8%、172（范围：77-422）天和 414（101-685）天。1 名患者在二线 S-IROX 治疗后接受了手术。二线 S-IROX 治疗被认为是可接受的。RD 设定在 1 级剂量（S-1，80mg/m；奥沙利铂，85mg/m；伊立替康，150mg/m）。
