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      Using a combination of fruquintinib, raltitrexed, and S-1 as a third-line treatment for metastatic colorectal cancer with co-existence of Hodgkin lymphoma: a case report

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          Abstract

          Background

          Patients with metastatic colorectal cancer (mCRC) beyond second line treatment have a poor prognosis. Fruquintinib, regorafenib, trifluridine/tipiracil (TAS-102), panitumumab and cetuximab combined with single-agent chemotherapy regimens are currently recommended as third-line therapies for patients exhibiting disease progression. Effective late-line therapies for mCRC are urgently needed. The FRESCO randomized clinical trial (RCT) prompts fruquintinib as a third-line treatment in advanced colorectal cancer (CRC). A phase II study in our center reported the efficacy and safety of S-1 plus raltitrexed for the treatment of chemo-refractory mCRC. The combination of the fruquintinib, raltitrexed, and S-1 has not been reported in mCRC.

          Case Description

          This case report presents a patient with mCRC who received third-line treatment with fruquintinib, raltitrexed, and S-1. A 54-year-old male presenting with hematochezia was admitted to West China Hospital of Sichuan University in June 2017 and underwent surgery for a tumor between the rectum and sigmoid colon. Postoperative pathology identified adenocarcinoma (wild-type RAS/RAF, no PIK3CA mutation), and the patient was diagnosed with mCRC (pathological stage, pT3pN1apM0). The mFOLFOX6 regimen was administered. The patient was subsequently diagnosed with Hodgkin lymphoma in May 2018 and treated with the ABVD regimen after multidisciplinary discussions. Liver metastases (intestinal-type adenocarcinoma) were detected in November 2018, and second-line therapy with the FOLFIRI regimen was initiated in January 2019. Lung metastases were identified in September 2019, so the patient was treated with a combination of raltitrexed, S-1, and fruquintinib. A partial response (PR) was detected in November 2019, and the patient underwent resection of the hepatic lesion on November 5, 2020. Computed tomography (CT) images in November 2021 revealed a stable disease; thus, raltitrexed was discontinued, and S-1 and fruquintinib were maintained. The treatment is still responding until the last follow-up (December 2022).

          Conclusions

          The case was characterized by the simultaneous existence of mCRC and Hodgkin lymphoma, which required management by a multidisciplinary team. Third-line therapy with fruquintinib, raltitrexed, and S-1 achieved a PR that permitted surgical resection and enabled a relatively long progression-free survival. The findings suggest that the three agents regimen might be clinically effective as late-line therapy for mCRC.

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          Most cited references17

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          Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up†

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            A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer.

            Panitumumab, a fully human antibody targeting the epidermal growth factor receptor, is active in patients with metastatic colorectal cancer (mCRC). This trial evaluated panitumumab added to bevacizumab and chemotherapy (oxaliplatin- and irinotecan-based) as first-line treatment for mCRC. Patients were randomly assigned within each chemotherapy cohort to bevacizumab and chemotherapy with or without panitumumab 6 mg/kg every 2 weeks. The primary end point was progression-free survival (PFS) within the oxaliplatin cohort. Tumor assessments were performed every 12 weeks and reviewed centrally. A total of 823 and 230 patients were randomly assigned to the oxaliplatin and irinotecan cohorts, respectively. Panitumumab was discontinued after a planned interim analysis of 812 oxaliplatin patients showed worse efficacy in the panitumumab arm. In the final analysis, median PFS was 10.0 and 11.4 months for the panitumumab and control arms, respectively (HR, 1.27; 95% CI, 1.06 to 1.52); median survival was 19.4 months and 24.5 months for the panitumumab and control arms, respectively. Grade 3/4 adverse events in the oxaliplatin cohort (panitumumab v control) included skin toxicity (36% v 1%), diarrhea (24% v 13%), infections (19% v 10%), and pulmonary embolism (6% v 4%). Increased toxicity without evidence of improved efficacy was observed in the panitumumab arm of the irinotecan cohort. KRAS analyses showed adverse outcomes for the panitumumab arm in both wild-type and mutant groups. The addition of panitumumab to bevacizumab and oxaliplatin- or irinotecan-based chemotherapy results in increased toxicity and decreased PFS. These combinations are not recommended for the treatment of mCRC in clinical practice.
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              Effect of Fruquintinib vs Placebo on Overall Survival in Patients With Previously Treated Metastatic Colorectal Cancer

              Patients with metastatic colorectal cancer (CRC) have limited effective and tolerable treatment options.
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                Author and article information

                Journal
                J Gastrointest Oncol
                J Gastrointest Oncol
                JGO
                Journal of Gastrointestinal Oncology
                AME Publishing Company
                2078-6891
                2219-679X
                21 February 2023
                28 February 2023
                : 14
                : 1
                : 450-457
                Affiliations
                [1]deptDepartment of Abdominal Cancer, Cancer Center , West China Hospital of Sichuan University , Chengdu, China
                Author notes

                Contributions: (I) Conception and design: Both authors; (II) Administrative support: D Luo; (III) Provision of study materials or patients: Both authors; (IV) Collection and assembly of data: Y Wan; (V) Data analysis and interpretation: Both authors; (VI) Manuscript writing: Both authors; (VII) Final approval of manuscript: Both authors.

                Correspondence to: Deyun Luo. Department of Abdominal Cancer, Cancer Center, West China Hospital of Sichuan University, Chengdu, China. Email: luodeyun999@ 123456163.com .
                Article
                jgo-14-01-450
                10.21037/jgo-23-39
                10007946
                36915460
                86e8af10-b0aa-4f1f-9e04-a698e8f6f863
                2023 Journal of Gastrointestinal Oncology. All rights reserved.

                Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0.

                History
                : 02 December 2022
                : 06 February 2023
                Categories
                Case Report

                colorectal cancer (crc),metastasis,chemotherapy,vascular endothelial growth factor receptor inhibitor (vegfr inhibitor),case report

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