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Efficacy of bevacizumab-containing chemotherapy in metastatic colorectal cancer and CXCL5 expression: Six case reports.

ABSTRACT: BACKGROUND:In metastatic colorectal cancer (mCRC), the anti-vascular endothelial growth factor drug bevacizumab (BVZ) plus chemotherapy significantly improves progression-free survival compared to chemotherapy (CT) alone. This benefit is not, however, observed in all patients. While increased chemokine CXCL5 gene expression promoting angiogenesis has been proposed as a prognostic mCRC biomarker, few studies have examined its relationship with drug efficacy. This study sought to analyze tumor CXCL5 gene expression in six patients with different efficacy of BVZ-containing CT in terms of the tumor response to treatment. CASE SUMMARY:We report six cases of stage IV KRAS-mutated mCRC. Patients were given first line treatment with BVZ-containing chemotherapy in University Hospital of Fuenlabrada. The six patients differed in terms of primary tumor location (right/left side), tumor burden (mostly hepatic and peritoneal disease) and clinical disease course. Before treatment onset, total RNA was isolated from paraffinated tumor biopsy specimens and CXCL5 gene expression quantified through conventional RT-qPCR procedures. Our main finding was that CXCL5 expression levels were several times higher in three patients with lower progression free survival (under 6 mo) from the start of treatment. CONCLUSION:A higher expression of CXCL5 was observed in the three patients showing worse tumor response to treatment.

SUBMITTER: Novillo A

PROVIDER: S-EPMC7201148 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Efficacy of bevacizumab-containing chemotherapy in metastatic colorectal cancer and <i>CXCL5</i> expression: Six case reports.

Novillo Apolonia A Gaibar María M Romero-Lorca Alicia A Gilsanz María Fuencisla MF Beltrán Laura L Galán Miguel M Antón Beatriz B Malón Diego D Moreno Amalia A Fernández-Santander Ana A

World journal of gastroenterology 20200401 16

<h4>Background</h4>In metastatic colorectal cancer (mCRC), the anti-vascular endothelial growth factor drug bevacizumab (BVZ) plus chemotherapy significantly improves progression-free survival compared to chemotherapy (CT) alone. This benefit is not, however, observed in all patients. While increased chemokine <i>CXCL5</i> gene expression promoting angiogenesis has been proposed as a prognostic mCRC biomarker, few studies have examined its relationship with drug efficacy. This study sought to an ...[more]

PMID: 32390708

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Project description:BackgroundAlthough bevacizumab is an important treatment for metastatic colorectal cancer (CRC), not all patients with CRC benefit from it; in unselected patient populations, only modest survival benefits have been reported.MethodsWe evaluated clinical outcomes in 110 patients using comprehensive molecular characterization to identify biomarkers for a response to bevacizumab-containing treatment. The molecular analysis comprised whole-exome sequencing, ribonucleic acid sequencing, and a methylation array on patient tissues.ResultsGenomic and molecular characterization was successfully conducted in 103 patients. Six of 103 CRC samples were hypermutated, and none of the non-hypermutant tumors were microsatellite unstable. Among those 103 patients, 89 had adenocarcinoma (ADC), 15 were diagnosed with mucinous ADC, and six had signet-ring cell carcinoma (SRCC). Consensus molecular subtype (CMS) 2 was unique to ADC. Of the four SRCCs, two were CMS1, one was CMS4, and the other was CMS3. APC mutation status was a significantly enriched factor in responders to bevacizumab treatment. Fibroblast growth factor receptor (FGFR) 1/2 signaling was upregulated in non-responders, whereas cell cycle, transfer ribonucleic acid processing, nucleotide excision repair, and oxidative phosphorylation pathways were enriched in responders. In addition, IGF1 was differentially expressed in non-responders (log2 fold change = -1.43, p = 4.11 × 10-5, false discovery rate = 0.098), and FLT1 was highly methylated in non-responders (p = 7.55 × 10-3). When the molecular pathways were reanalyzed separately according to the backbone chemotherapy (FOLFOX vs. FOLFIRI), the significance of the molecular pathways varied according to the backbone chemotherapy.ConclusionsThis study sought a subset of CRC patients with a distinct clinical response to chemotherapy containing bevacizumab. Our results need to be validated in a large group of homogenous patient cohort and examined according to the different chemotherapy backbones to create personalized therapeutic opportunities in CRC.

Project description:ImportanceTriplet chemotherapy with fluorouracil, folinic acid, oxaliplatin, and irinotecan plus bevacizumab (FOLFOXIRI-B) is an effective first-line treatment option for patients with metastatic colorectal cancer (mCRC). However, the degree of implementation of FOLFOXIRI-B in daily practice is unknown.ObjectivesTo evaluate the current adoption rate of FOLFOXIRI-B in patients with mCRC and investigate the perspectives of medical oncologists toward this treatment option.Design, setting, and participantsThis 1-week, multicenter, cross-sectional study in the Netherlands used a flash mob design, which facilitates ultrafast data generation (flash) through the engagement of numerous researchers (mob). During the study week (March 1-5, 2021), patient data were retrieved from electronic health records of 47 hospitals on patients with mCRC who were referred to a medical oncologist between November 1, 2020, and January 31, 2021. Interviews were simultaneously conducted with 101 medical oncologists from 52 hospitals who regularly treat patients with mCRC.ExposureFirst-line systemic treatment as determined by the treating physician.Main outcomes and measuresThe FOLFOXIRI-B prescription rate was the main outcome. Current practice was compared with prescription rates in 2015 to 2018. Eligibility for treatment with FOLFOXIRI-B was estimated. An exploratory outcome was medical oncologists' reported perspectives on FOLFOXIRI-B.ResultsA total of 5948 patients in the Netherlands (median age [interquartile range], 66 [57-73] years; 3503 [59%] male; and 3712 [62%] with left-sided or rectal tumor) were treated with first-line systemic therapy for synchronous mCRC. A total of 282 patients with mCRC underwent systemic therapy during the study period (2021). Of these 282 patients, 199 (71%) were treated with intensive first-line therapy other than FOLFOXIRI-B, of whom 184 (65%) were treated with oxaliplatin doublets with or without bevacizumab; 14 (5%) with irinotecan doublets with or without bevacizumab, panitumumab, or cetuximab; and 1 (0.4%) with irinotecan with bevacizumab. Fifty-four patients (19%) were treated with fluoropyrimidine monotherapy with or without bevacizumab, 1 patient (0.4%) with panitumumab monotherapy, and 3 (1%) with immune checkpoint inhibitors. In total, 25 patients (9%; 95% CI, 6%-12%) were treated with first-line FOLFOXIRI-B compared with 142 (2%; 95% CI, 2%-3%) in 2015 to 2018. During the study period, 21 of 157 eligible patients (13.4%) in the Netherlands were treated with FOLFOXIRI-B. A total of 87 medical oncologists (86%) reported discussing FOLFOXIRI-B as a treatment option with eligible patients. A total of 47 of 85 (55%) generally communicated a preference for a chemotherapy doublet to patients. These oncologists reported a significantly lower awareness of guidelines and trial results. Toxic effects were the most reported reason to prefer an alternative regimen.Conclusions and relevanceThe findings of this study suggest that FOLFOXIRI-B prescription rates have marginally increased in the last 5 years. Considering that most medical oncologists discuss this treatment option, the prescription rate found in this study was below expectations. Awareness of guidelines and trial data seems to contribute to the discussion of available treatment options by medical oncologists, and the findings of this study suggest a need for repeated and continuing medical education.

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Efficacy of bevacizumab-containing chemotherapy in metastatic colorectal cancer and CXCL5 expression: Six case reports.

Publications

Efficacy of bevacizumab-containing chemotherapy in metastatic colorectal cancer and <i>CXCL5</i> expression: Six case reports.

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