Combination of Anti-EGFR and Anti-VEGF Drugs for the Treatment of Previously Treated Metastatic Colorectal Cancer: A Case Report and Literature Review

Li, Yong; Chen, Xian; Li, Wenzhu; Ye, Yongsong; Du, Xuemin; Sun, Shaodan; Liu, Lirong; Zhang, Haibo

doi:10.3389/fonc.2021.684309

Cited by 11 publications

(10 citation statements)

References 27 publications

(38 reference statements)

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“…The patient described in this case report exhibited a PR to treatment with this combination of drugs that allowed him to meet the indications for surgery and achieve a long PFS. The potential bene ts of fruquintinib-based combination therapies are supported by another case report describing a patient with mCRC who was successfully treated with cetuximab and fruquintinib [14]. Nevertheless, the patient in the present study developed lung metastases during treatment.…”

Section: Discussionsupporting

confidence: 62%

The combination of fruquintinib, raltitrexed and S-1 as a third-line treatment for metastatic colorectal cancer: A case report

Wan

Luo

2022

Preprint

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Effective late-line therapies for metastatic colorectal cancer (mCRC) are urgently needed. 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 our hospital 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 the combination of raltitrexed, S-1 and fruquintinib. A partial response was detected in November 2019, and the patient underwent resection of the hepatic lesion on November 5, 2020. CT images in November 2021 revealed stable disease, thus raltitrexed was discontinued and S-1 and fruquintinib was maintained. The patient remains alive at the time of writing. 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 partial response that permitted surgical resection as well as a relatively long progression-free survival. This regimen may have potential as a late-line therapy for mCRC.

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Section: Discussionsupporting

confidence: 62%

The combination of fruquintinib, raltitrexed and S-1 as a third-line treatment for metastatic colorectal cancer: A case report

Wan

Luo

2022

Preprint

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“…In addition, combined therapy did not reduce tumor-infiltrating Treg cells but transformed them into an effector phenotype that expresses a Th1 signature and cooperates with CD8 T cells to kill CT-26 tumor cells through TCR-MHC engagement-dependent mechanisms. These immune responses are likely enhanced by the induced expression of type I IFN gene signatures, which are known to elicit chemotherapydependent antitumor immunity through several mechanisms, including promoting cross-priming, supporting cytotoxic T lymphocyte and immune effector functions, and releasing In the recent past, TPI was used in clinical trials in combination with checkpoint blockers, viz., bevacizumab and cetuximab, in patients with colorectal cancers (36,52). However, these attempts were performed using pMMR-MSI-L type CRC.…”

Section: Discussionmentioning

confidence: 99%

“…In the recent past, TPI was used in clinical trials in combination with checkpoint blockers, viz., bevacizumab and cetuximab, in patients with colorectal cancers ( 36 , 52 ). However, these attempts were performed using pMMR-MSI-L type CRC.…”

Section: Discussionmentioning

confidence: 99%

Targeting thymidine phosphorylase alleviates resistance to dendritic cell immunotherapy in colorectal cancer and promotes antitumor immunity

et al. 2022

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T-cell exhaustion plays a pivotal role in the resistance of microsatellite-stable colorectal cancer (CRC) to immunotherapy. Identifying and targeting T-cell exhaustion-activating mechanisms is a promising strategy to augment the effects of immunotherapy. Here, we found that thymidine phosphorylase (TYMP) plays a decisive role in inducing systemic T-cell exhaustion and abrogating the efficacy of dendritic cell (DC) therapy in a CRC model. Targeting TYMP with tipiracil hydrochloride (TPI) induces immunological cell death (ICD). The combined effects of TPI and imiquimod-activated DCs turn CT26 tumors into immunologically ‘hot’ tumors by inducing ICD in vivo. High-dimensional cytometry analysis revealed T-cell and IFN-γ dependency on the therapeutic outcome. In addition, chemoimmunotherapy converts intratumoral Treg cells into Th1 effector cells and eliminates tumor-associated macrophages, resulting in higher cytotoxic T lymphocyte infiltration and activation. This effect is also associated with the downregulation of PD-L1 expression in tumors, leading to the prevention of T-cell exhaustion. Thus, cooperative and cognitive interactions between dendritic cells and immunogenic cell death induced by therapy with TPI promote the immune response and tumoricidal activities against microsatellite stable colorectal cancer. Our results support TYMP targeting to improve the effects of DC immunotherapy and outcomes in CRC.

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“…This combination therapy is adopted as single anti-angiogenic therapy was faced with resistance and even promoted metastasis [ 73 ]. Accordingly, a case study reported successful treatment of a CRC patient with RAS/BRAF wild-type using a combination of anti-VEGF (fruquintinib) and anti-EGFR (cetuximab) drugs for the treatment of previously treated metastatic CRC, after resistance to chemotherapy, cetuximab, bevacizumab, and regorafenib [ 74 ].…”

Section: Drug Resistance Mechanisms In Crcmentioning

confidence: 99%

Recent advances in targeted drug delivery systems for resistant colorectal cancer

et al. 2022

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Colorectal cancer (CRC) is one of the deadliest cancers in the world, the incidences and morality rate are rising and poses an important threat to the public health. It is known that multiple drug resistance (MDR) is one of the major obstacles in CRC treatment. Tumor microenvironment plus genomic instability, tumor derived exosomes (TDE), cancer stem cells (CSCs), circulating tumor cells (CTCs), cell-free DNA (cfDNA), as well as cellular signaling pathways are important issues regarding resistance. Since non-targeted therapy causes toxicity, diverse side effects, and undesired efficacy, targeted therapy with contribution of various carriers has been developed to address the mentioned shortcomings. In this paper the underlying causes of MDR and then various targeting strategies including exosomes, liposomes, hydrogels, cell-based carriers and theranostics which are utilized to overcome therapeutic resistance will be described. We also discuss implication of emerging approaches involving single cell approaches and computer-aided drug delivery with high potential for meeting CRC medical needs.

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Combination of Anti-EGFR and Anti-VEGF Drugs for the Treatment of Previously Treated Metastatic Colorectal Cancer: A Case Report and Literature Review

Cited by 11 publications

References 27 publications

The combination of fruquintinib, raltitrexed and S-1 as a third-line treatment for metastatic colorectal cancer: A case report

The combination of fruquintinib, raltitrexed and S-1 as a third-line treatment for metastatic colorectal cancer: A case report

Targeting thymidine phosphorylase alleviates resistance to dendritic cell immunotherapy in colorectal cancer and promotes antitumor immunity

Recent advances in targeted drug delivery systems for resistant colorectal cancer

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