Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
Department of Surgical Oncology, UT MD Anderson Cancer Center, Houston, TX, USA.
Ann Surg Oncol. 2023 Oct;30(11):6558-6566. doi: 10.1245/s10434-023-13809-5. Epub 2023 Jun 27.
Most patients with intrahepatic cholangiocarcinoma (IHCC) develop recurrence after resection. Adjuvant capecitabine remains the standard of care for resected IHCC. A combination of gemcitabine, cisplatin, and nab-paclitaxel (GAP) was associated with a 45% response rate and 20% conversion rate among patients with unresectable biliary tract cancers. The aim of this study was to evaluate the feasibility of delivering GAP in the neoadjuvant setting for resectable, high-risk IHCC.
A multi-institutional, single-arm, phase II trial was conducted for patients with resectable, high-risk IHCC, defined as tumor size > 5 cm, multiple tumors, presence of radiographic major vascular invasion, or lymph node involvement. Patients received preoperative GAP (gemcitabine 800 mg/m, cisplatin 25 mg/m, and nab-paclitaxel 100 mg/m on days 1 and 8 of a 21-day cycle) for a total of 4 cycles prior to an attempt at curative-intent surgical resection. The primary endpoint was completion of both preoperative chemotherapy and surgical resection. Secondary endpoints were adverse events, radiologic response, recurrence-free survival (RFS), and overall survival (OS).
Thirty evaluable patients were enrolled. Median age was 60.5 years. Median follow-up for all patients was 17 months. Ten patients (33%) experienced grade ≥ 3 treatment-related adverse events, the most common being neutropenia and diarrhea; 50% required ≥ 1 dose reduction. The disease control rate was 90% (progressive disease: 10%, partial response: 23%, stable disease: 67%). There was zero treatment-related mortality. Twenty-two patients (73%, 90% CI 57-86; p = 0.008) completed all chemotherapy and surgery. Two patients (9%) who successfully underwent resection had minor postoperative complications. Median length of hospital stay was 4 days. Median RFS was 7.1 months. Median OS for the entire cohort was 24 months and was not reached in patients who underwent surgical resection.
Neoadjuvant treatment with gemcitabine, cisplatin, and nab-paclitaxel is feasible and safe prior to resection of intrahepatic cholangiocarcinoma and does not adversely impact perioperative outcomes.
大多数肝内胆管癌（IHCC）患者在手术后会复发。对于接受手术的 IHCC 患者，卡培他滨辅助治疗仍然是标准治疗方案。吉西他滨、顺铂和nab-紫杉醇（GAP）联合治疗不可切除胆道癌患者的缓解率为 45%，转化率为 20%。本研究旨在评估 GAP 在可切除高危 IHCC 新辅助治疗中的可行性。
对可切除高危 IHCC 患者（肿瘤大小>5cm、多个肿瘤、存在影像学大血管侵犯或淋巴结受累）进行多机构、单臂、二期临床试验。患者接受术前 GAP（吉西他滨 800mg/m²，顺铂 25mg/m²，nab-紫杉醇 100mg/m²，于 21 天周期的第 1 和第 8 天）治疗，共 4 个周期，然后尝试进行根治性手术切除。主要终点是完成术前化疗和手术切除。次要终点是不良事件、影像学反应、无复发生存（RFS）和总生存（OS）。
30 例可评估患者入组。中位年龄为 60.5 岁。所有患者的中位随访时间为 17 个月。10 例患者（33%）发生≥3 级治疗相关不良事件，最常见的是中性粒细胞减少和腹泻；50%需要≥1 次剂量减少。疾病控制率为 90%（进展性疾病：10%，部分缓解：23%，稳定疾病：67%）。无治疗相关死亡。22 例患者（73%，90%CI 57-86；p=0.008）完成了所有化疗和手术。2 例（9%）成功接受手术切除的患者仅有轻微的术后并发症。中位住院时间为 4 天。中位 RFS 为 7.1 个月。全组中位 OS 为 24 个月，接受手术切除的患者未达到。
吉西他滨、顺铂和 nab-紫杉醇新辅助治疗在切除肝内胆管癌之前是可行且安全的，不会对围手术期结果产生不利影响。
