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经肝动脉灌注治疗不可切除结直肠癌肝转移患者的改良氟尿苷低剂量方案。

A Modified Floxuridine Reduced-Dose Protocol for Patients with Unresectable Colorectal Liver Metastases Treated with Hepatic Arterial Infusion.

机构信息

Department of Surgery, Division of Surgical Oncology, Knight Cancer Institute, Oregon Health & Science University (OHSU), Portland, OR, USA.

Department of Medicine, Division of Hematology and Medical Oncology, Knight Cancer Institute, OHSU, Portland, OR, USA.

出版信息

Ann Surg Oncol. 2024 Oct;31(10):6537-6545. doi: 10.1245/s10434-024-15729-4. Epub 2024 Jul 12.

Abstract

BACKGROUND

Most patients treated with the standard dosing protocol (SDP) of hepatic arterial infusion (HAI) floxuridine require dose holds and reductions, thereby limiting their HAI therapy. We hypothesized that a modified dosing protocol (MDP) with a reduced floxuridine starting dose would decrease dose holds, dose reductions, and have similar potential to convert patients with unresectable colorectal liver metastases (uCRLM) to resection.

PATIENTS AND METHODS

We reviewed our institutional database of patients with uCRLM treated with HAI between 2016 and 2022. In 2019, we modified the floxuridine starting dose to 50% (0.06 mg/kg) of the SDP (0.12 mg/kg). We compared treatment related outcomes between the SDP and MDP cohorts.

RESULTS

Of n = 33 patients, 15 (45%) were treated on the SDP and 18 (55%) with our new institutional MDP. The MDP cohort completed more cycles before a dose reduction (mean 4.2 vs. 2), received more overall cycles (median 7.5 vs. 5), and averaged 39 more days of treatment (all P < 0.05). The SDP experienced more dose reductions (1.4 vs. 0.61) and dose holds (1.2 vs. 0.2; both P < 0.01). Of the patients in each group potentially convertible to hepatic resection, three patients (23%) in the SDP and six patients (35%) in the MDP group converted to resection (P = 0.691). Overall, four patients (27%) in the SDP developed treatment ending biliary toxicity compared with one patient (6%) in the MDP.

CONCLUSIONS

A 50% starting dose of HAI floxuridine provides fewer treatment disruptions, more consecutive floxuridine cycles, and a similar potential to convert patients with initially uCRLM for disease clearance.

摘要

背景

大多数接受标准剂量方案(SDP)肝动脉输注(HAI)氟尿嘧啶治疗的患者需要剂量暂停和减少,从而限制了他们的 HAI 治疗。我们假设,降低氟尿嘧啶起始剂量的改良剂量方案(MDP)将减少剂量暂停和减少,并具有类似的潜力将不可切除结直肠癌肝转移(uCRLM)患者转化为可切除。

患者和方法

我们回顾了我们机构 2016 年至 2022 年期间接受 HAI 治疗的 uCRLM 患者的数据库。2019 年,我们将氟尿嘧啶的起始剂量降低至 SDP(0.12mg/kg)的 50%(0.06mg/kg)。我们比较了 SDP 和 MDP 队列之间的治疗相关结局。

结果

n = 33 例患者中,15 例(45%)接受 SDP 治疗,18 例(55%)接受我们新的机构 MDP 治疗。MDP 队列在剂量减少前完成了更多的周期(平均 4.2 对 2),接受了更多的总周期(中位数 7.5 对 5),并平均延长了 39 天的治疗(均 P < 0.05)。SDP 经历了更多的剂量减少(1.4 对 0.61)和剂量暂停(1.2 对 0.2;均 P < 0.01)。在每个组中,有潜在可转化为肝切除术的患者中,SDP 组中有 3 例(23%),MDP 组中有 6 例(35%)转化为切除术(P = 0.691)。总的来说,SDP 组中有 4 例(27%)患者发生了治疗结束时的胆道毒性,而 MDP 组中只有 1 例(6%)患者发生了这种情况。

结论

HAI 氟尿嘧啶的 50%起始剂量可减少治疗中断,增加连续氟尿嘧啶周期,并具有类似的潜力将最初患有 uCRLM 的患者转化为疾病清除。

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