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

Abstract

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. 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. 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). 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. 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.