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肝动脉化疗栓塞术联合FOLFIRI化疗用于一线治疗具有癌基因突变的转移性结直肠癌患者的疗效和安全性

Efficacy and Safety of Liver Chemoembolization Procedures, Combined with FOLFIRI Chemotherapy, in First-Line Treatment of Metastatic Colorectal Cancer in Patients with Oncogene Mutations.

作者信息

Szemitko Marcin, Falkowski Aleksander, Modrzejewska Monika, Golubinska-Szemitko Elzbieta

机构信息

Department of Interventional Radiology, Pomeranian Medical University, Al. Pow. Wielkopolskich 72, 70-111 Szczecin, Poland.

II Department of Ophthalmology, Pomeranian Medical University, Al. Pow. Wielkopolskich 72, 70-111 Szczecin, Poland.

出版信息

Cancers (Basel). 2023 Dec 22;16(1):71. doi: 10.3390/cancers16010071.

Abstract

PURPOSE

The usual first- and second-line treatments for inoperable liver metastases from colorectal cancer (CRC) involve systemic chemotherapy, often with molecular targeted therapy. Chemoembolization, using microspheres loaded with irinotecan, has also been available as a treatment option for many years, used mainly in later lines of treatment when, due to increasing resistance, other chemotherapy regimens may have been exhausted. However, when there are contraindications to molecular therapies, the use of chemoembolization as first or second lines of treatment, in combination with FOLFIRI chemotherapy, may provide greater efficacy due to reduced irinotecan resistance.

OBJECTIVE

The aim of the study was to evaluate the efficacy and safety of transarterial chemoembolization (DEB-TACE) procedures for the treatment of metastatic liver lesions from CRC, using irinotecan-loaded microspheres as first-line treatment together with FOLFIRI chemotherapy.

PATIENTS AND METHODS

The analysis included 20 patients (12 females; 8 males) with unresectable liver metastases in the course of CRC with KRAS, NRAS and BRAF mutations, who underwent 73 chemoembolization procedures with microspheres loaded with 100 mg of irinotecan, in combination with interspersed FOLFIRI chemotherapy. Response to treatment was assessed through computed tomography according to the Modified Response Evaluation Criteria in Solid Tumors (mRECIST). Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Assessment of adverse events utilized the Cancer Therapy Evaluation Program's Common Terminology Criteria for Adverse Events (CTCAE; version 5.0).

RESULTS

Partial remission (PR) was observed in 11 (55%) patients while 5 (25%) patients showed stable disease (SD). Progression (PD) was observed in 4 (20%) patients. Median PFS was 9.1 months (95% CI: 7.2-10.1 months) and median OS was 20.7 months (95% CI: 18.2-23.3 months). The most common adverse events (AEs) resulting in treatment delay were hematological disorders, notably neutropenia (CTCAE grades 1-3). No deaths or AEs above grade 3 occurred during TACE. Continued FOLFIRI chemotherapy after TACE treatments resulted in grade 4 neutropenia in two patients, grade 3 in four patients and grade 2 thrombocytopenia in two patients.

CONCLUSION

Combining FOLFIRI chemotherapy with chemoembolization procedures for liver metastatic lesions from colorectal cancer may provide a valuable treatment option for patients not qualified for monoclonal antibody therapy.

摘要

目的

结直肠癌(CRC)不可切除肝转移的常用一线和二线治疗包括全身化疗,通常联合分子靶向治疗。使用载有伊立替康的微球进行化疗栓塞多年来也一直是一种治疗选择,主要用于后期治疗,此时由于耐药性增加,其他化疗方案可能已用尽。然而,当存在分子治疗的禁忌证时,将化疗栓塞作为一线或二线治疗并联合FOLFIRI化疗,可能因降低伊立替康耐药性而提供更高的疗效。

目的

本研究的目的是评估使用载有伊立替康的微球作为一线治疗并联合FOLFIRI化疗的经动脉化疗栓塞(DEB-TACE)程序治疗CRC肝转移灶的疗效和安全性。

患者和方法

分析纳入20例(12例女性;8例男性)患有不可切除肝转移的CRC患者,伴有KRAS、NRAS和BRAF突变,接受了73次用载有100mg伊立替康的微球进行的化疗栓塞程序,并穿插FOLFIRI化疗。根据实体瘤改良反应评估标准(mRECIST)通过计算机断层扫描评估治疗反应。使用Kaplan-Meier方法计算无进展生存期(PFS)和总生存期(OS)。利用癌症治疗评估计划的不良事件通用术语标准(CTCAE;第5.0版)评估不良事件。

结果

11例(55%)患者观察到部分缓解(PR),5例(25%)患者疾病稳定(SD)。4例(20%)患者出现疾病进展(PD)。中位PFS为9.1个月(95%CI:7.2 - 10.1个月),中位OS为20.7个月(95%CI:18.2 - 23.3个月)。导致治疗延迟的最常见不良事件(AE)是血液系统疾病,尤其是中性粒细胞减少(CTCAE 1 - 3级)。TACE期间未发生3级以上的死亡或AE。TACE治疗后继续进行FOLFIRI化疗导致2例患者出现4级中性粒细胞减少,4例患者出现3级,2例患者出现2级血小板减少。

结论

将FOLFIRI化疗与CRC肝转移灶的化疗栓塞程序相结合,可能为不符合单克隆抗体治疗条件的患者提供一种有价值的治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8947/10778126/22ffe6ef1112/cancers-16-00071-g001.jpg

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