scholarly journals Prognostic role of a new index (multi inflammatory index) in patients with metastatic colorectal cancer: results from the randomized ITACa trial

2020 ◽  
Vol 12 ◽  
pp. 175883592095836
Author(s):  
Andrea Casadei Gardini ◽  
Emanuela Scarpi ◽  
Martina Valgiusti ◽  
Manlio Monti ◽  
Silvia Ruscelli ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Predictive Capacity ◽  
Lymphocyte Ratio ◽  
Inflammatory Index ◽  
Reactive Protein ◽  
Clinical Covariates ◽  
Registration Date

Aims: We created a new index (Multi Inflammatory Index, MII) composed of an inflammatory index [neutrophil-to lymphocyte-ratio (NLR): MII-1; platelet-to-lymphocyte ratio (PLR): MII-2; or systemic immune-inflammation index (SII): MII-3] and C-reactive protein (CRP). Our aim was to evaluate the prognostic and/or predictive capacity of the MII in the randomized ITACa (Italian Trial in Advanced Colorectal Cancer) study on patients with metastatic colorectal cancer undergoing first-line chemotherapy. Methods: Between November 2007 and March 2012, baseline NLR, PLR; SII and CRP were available for 131 patients, 66 receiving chemotherapy plus bevacizumab and 65 receiving chemotherapy alone. Results: Patients with low (<25) MII-1 levels had a better outcome than those with high (⩾25) levels: median progression-free survival (PFS) was 12.4 versus 8.9 months [hazard ratio (HR) = 1.74, 95% confidence interval (CI) 1.21–2.51, p = 0.003] and median overall survival (OS) was 30.9 months versus 15.0 months (HR = 2.05, 95% CI 1.40–3.02, p = 0.0002), respectively. Similar results were obtained for patients with low (<1424) MII-2 levels compared with those with high (⩾1424) levels: median PFS was 12.6 versus 8.9 months (HR = 1.95, 95% CI 1.35–2.82, p = 0.0004) and median OS was 32.4 versus 14.6 months, respectively (HR = 2.42, 95% CI 1.64–3.57, p < 0.0001). Patients with low (<6068) MII-3 levels had a longer median PFS and OS than those with high (⩾6068) levels: 12.6 versus 8.9 months (HR = 1.91, 95% CI 1.33–2.76, p = 0.005) and 30.9 versus15.0 months (HR = 2.10, 95% CI 1.43–3.09, p = 0.0002), respectively. Following adjustment for clinical covariates, multivariate analysis confirmed all MII indexes as independent prognostic factors for predicting PFS and OS. Conclusion: All MII indexes appear to be useful as prognostic markers. Trial registration ClinicalTrials.gov identifier: NCT01878422 (registration date: 07/06/2013) https://clinicaltrials.gov/ct2/show/NCT01878422

Ziv-aflibercept: A novel angiogenesis inhibitor for the treatment of metastatic colorectal cancer

2013 ◽  
Vol 70 (21) ◽  
pp. 1887-1896 ◽  
Author(s):  
Clement Chung ◽  
Nisha Pherwani
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Performance Status ◽  
Angiogenesis Inhibitor ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Second Line ◽  
Patient Response ◽  
Line Setting

Abstract Purpose The pharmacology, pharmacokinetics, clinical efficacy, safety, and administration of ziv-aflibercept in combination therapy for metastatic colorectal cancer (mCRC) are reviewed. Summary Ziv-aflibercept (Zaltrap, Regeneron Pharmaceuticals and sanofi-aventis) is a novel recombinant fusion protein that targets the angiogenesis signaling pathway of tumor cells by blocking vascular endothelial growth factor (VEGF) receptors that play a key role in tumor growth and metastasis; it is a more potent VEGF blocker than bevacizumab. Ziv-aflibercept is approved by the Food and Drug Administration for use in combination with fluorouracil, irinotecan, and leucovorin (the FOLFIRI regimen) for second-line treatment of patients with mCRC who have disease progression during first-line oxaliplatin-based chemotherapy. A Phase III trial demonstrated that relative to FOLFIRI therapy alone, the use of ziv-aflibercept was associated with significantly improved patient response, overall survival, and progression-free survival in patients with good performance status at baseline, including some who had received prior bevacizumab therapy. The most common grade 3 or 4 adverse effects associated with ziv-aflibercept use in clinical studies were neutropenia, hypertension, and diarrhea; the U.S. product labeling warns of potential hemorrhage and other treatment-related risks. Conclusion Current clinical data are insufficient to directly compare ziv-aflibercept and bevacizumab when used with standard combination chemotherapy as first- or second-line regimens for mCRC. The role of ziv-aflibercept is currently limited to the second-line setting in combination with irinotecan-based regimens in mCRC patients who have not received irinotecan previously. The role of ziv-aflibercept in chemotherapy for other tumor types is yet to be determined.

scholarly journals Prognostic role of aspartate aminotransferase-lymphocyte ratio index in patients with metastatic colorectal cancer: results from the randomized ITACa trial

2018 ◽  
Vol Volume 11 ◽  
pp. 5261-5268 ◽  
Author(s):  
Andrea Casadei Gardini ◽  
Emanuela Scarpi ◽  
Elena Orlandi ◽  
Davide Tassinari ◽  
Silvana Leo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Aspartate Aminotransferase ◽  
Prognostic Role ◽  
Lymphocyte Ratio

scholarly journals Aflibercept in the Treatment of Metastatic Colorectal Cancer

2012 ◽  
Vol 6 ◽  
pp. CMO.S7432 ◽  
Author(s):  
Tzu-Fei Wang ◽  
Albert Craig Lockhart
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Free Survival ◽  
The Third ◽  
Common Cancer ◽  
The Us

Colorectal cancer is the third most common cancer in the US. In recent decades, an improved understanding of the role of the angiogenesis pathway in colorectal cancer has led to advancements in treatment. Bevacizumab has been shown to improve the progression-free survival and overall survival when combined with cytotoxic chemotherapy in patients with metastatic colorectal cancer, and at present is the only antiangiogenesis agent approved for the treatment of this cancer. Aflibercept is a novel angiogenesis-targeting agent, and has demonstrated efficacy in treating metastatic colorectal cancer in a recent randomized Phase III trial. Here we review the role of angiogenesis in the tumorigenesis of colorectal cancer, strategies for targeting angiogenesis, and the clinical development of aflibercept.

scholarly journals Prognostic Value of Sarcopenia in Metastatic Colorectal Cancer Patients Treated with Trifluridine/Tipiracil

2021 ◽  
Vol 10 (21) ◽  
pp. 5107
Author(s):  
Mateusz Malik ◽  
Maciej Michalak ◽  
Barbara Radecka ◽  
Marek Gełej ◽  
Aleksandra Jackowska ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Skeletal Muscle ◽  
Metastatic Colorectal Cancer ◽  
Performance Status ◽  
Lumbar Vertebra ◽  
Progression Free Survival ◽  
Muscle Area ◽  
Skeletal Muscle Index ◽  
Skeletal Mass

Sarcopenia is common in metastatic colorectal cancer (mCRC), increases the risk of treatment-related toxicity and reduces survival. Trifluridine/tipiracil (TT) chemotherapy significantly improved survival in refractory mCRC patients, but the prognostic and predictive role of pretherapeutic sarcopenia and variation in the skeletal muscle index (SMI) during this treatment has not been investigated so far. In this retrospective, observational study, clinical data on mCRC patients treated with TT at six cancer centres in Poland were collected. Computed tomography (CT) scans acquired at the time of initiation of TT (CT1) and on the first restaging (CT2), were evaluated. SMI was assessed based on the skeletal muscle area (SMA) at the level of the third lumbar vertebra. Progression-free survival (PFS) and overall survival (OS) were calculated from the treatment start. Neither initial sarcopenia nor ≥5% skeletal mass loss (SML) between CT1 and CT2 had a significant effect on PFS in treated patients (p = 0.5526 and p = 0.1092, respectively). In the multivariate analysis, reduced OS was found in patients with ≥5% SML (HR: 2.03 (1.11–3.72), p = 0.0039). We describe the prognostic role of sarcopenia beyond second line treatment and analyze other factors, such as performance status, tumor histological differentiation or carcinoembryonic antigen level that could predict TT treatment response.

Association of a polymorphism in amphiregulin with worse prognosis in metastatic colorectal cancer patients treated with cetuximab.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14543-e14543
Author(s):  
Peter M. D. Wilson ◽  
Takeru Wakatsuki ◽  
Fotios Loupakis ◽  
Wu Zhang ◽  
Dongyun Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Direct Dna Sequencing ◽  
Predictive Role ◽  
Third Line ◽  
Colorectal Cancer Patients ◽  
Gene Expression Levels

e14543 Background: Accumulating data suggests that Amphiregulin (AREG) and Epiregulin (EREG), ligands of the EGFR pathway, are potential prognostic and predictive markers in metastatic colorectal cancer (mCRC). Elevated AREG and EREG gene expression levels are predictive of improved response rates in mCRC patients treated with cetuximab and longer overall survival (OS) in patients with mCRC who did not receive cetuximab. Since polymorphisms in AREG and EREG may affect their expression or function, we tested whether AREG and EREG polymorphisms were associated with clinical outcome in mCRC patients treated with cetuximab. Methods: Seventy-three patients (n=73) with histopathologically-confirmed mCRC with Kras/Braf wild type were enrolled in Italy. These patients were treated with cetuximab monotherapy or irinotecan plus cetuximab as second or third line treatment. Genomic DNA was extracted from blood and 4 SNPs in AREG and 5 SNPs in EREG were analyzed by direct DNA-sequencing. Results: The median follow-up period was 13.3 months in this cohort. The median progression-free survival (PFS) and OS were 5.2 and 12.9 months respectively. The results indicate that the intronic AREG polymorphism rs28364983 A/C was associated with shorter PFS and OS. Patients with homozygous C/C (n=2) showed a median PFS of 2.3 months vs. 5.3 months for patients harboring at least one-A allele (n=71) (HR: 4.26 [95%CI: 0.98-18.5], p=0.05). Patients with homozygous C/C showed a median OS of 3.0 months vs. 13.1 months for patients harboring at least one-A allele (HR: 3.98 [95%CI: 0.93-16.9], p=0.062). An independent cohort of thirty-three patients was used to validate these initial findings and showed that patients with homozygous C/C (n=3) had a median PFS of 2.3 months vs. 3.8 months for patients harboring at least one-A allele (n=103) (HR: 3.79 [95%CI: 1.16-12.3], p=0.027) and a median OS of 3.0 months vs. 8.4 months (HR: 3.01 [95%CI: 0.93-9.71], p=0.065), respectively. Conclusions: AREG rs28364983 predicted worse outcome in mCRC patients treated with cetuximab; however, further analyses are necessary to understand the mechanism and further validate the prognostic and/or predictive role of this polymorphism.

The prognostic value of systemic inflammatory factors in BRAF (V600E) mutant metastatic colorectal cancer (mCRC).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 622-622
Author(s):  
Nieves Martinez Lago ◽  
Marta Covela Rúa ◽  
Elena Brozos Vazquez ◽  
Ana Fernandez Fernandez Montes ◽  
Juan Cruz de la Cámara Gómez ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factors ◽  
Metastatic Colorectal Cancer ◽  
Tumor Resection ◽  
Progression Free Survival ◽  
Braf V600e ◽  
Inflammatory Factors ◽  
Prognostic Impact ◽  
Multicentric Study ◽  
Lymphocyte Ratio

622 Background: Multiple studies have reported prognostic association of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLT) and albumin levels including patients with early and advanced metastatic colorectal cancer. However, it is unknown the prognostic impact in patients with BRAF (V600E) mutant metastatic colorectal cancer (mCRC). Methods: We conducted an observational, retrospective, multicentric study of patients with BRAF V600E-mt mCRC treated at nine university Spanish hospitals belonging to GITuD (Galician Research Group on Digestive Tumors). Demographic, clinic, pathological characteristics, overall survival (OS) and progression free survival (PFS) data were retrospectively analyzed. Results: Data from 65 pts. treated between November 2010 to June 2018 were recorded. Median age was 62.8 years (range 30-83), 55.4 % female, 75.4% ECOG PS0-1, 49.2% right-sided, 35.2% high grade, 69.2% synchronous presentation, 66.2% primary tumor resection and median metastatic locations was 2 (range 1-5). With a median follow up of 64.6 months, median OS was 12.9 months (95% CI, 9.8-16.0) and first line PFS was 4.1 months (95% CI, 2.7-5.5). NLR (HR 2.294; p = 0.004), PLR (HR 6.329; p = 0.028) and albumin levels (HR 2.575, p = 0.011) were independent prognostic factors for OS. Patients with higher NLR (> 3 vs. < 3): had a significantly lower OS 6.8 versus 17.5 months (HR 2.294; 95% CI 1.3-4.1, p = 0.004), which was also true for patients with higher PLR (> 200 vs. < 200): with OS 6.3 versus 14.5 months (HR 1.879; 95% CI 1.1-3.3, p = 0.028), while patients with low albumin had lower OS 6.8 versus 13.4 months (HR 2.575; 95% CI 1.2-5.5, p = 0.011). NLR was positively associated with PLR (p < 0.001). Neither NLR (p = 0.190) or PLR (p = 0.327) were associated with low albumin levels. A Systemic Inflammation Score (assigning one point for each factor) was predictive of survival: OS 0/1/2/3 factors were 17.7 versus 8.7 versus 9.7 versus 5.0 months (p < 0.001). Patients with Systemic Inflamation Score = 0 had significantly higher OS: 17.7 versus 8.2 months (HR 0.357; 95% CI 0.2-0.7, p = 0.001). Conclusions: NLR, PLR and albumin levels are significant prognostic factors in patients with BRAF V600E-mt mCRC.

Sign in / Sign up

Export Citation Format

Share Document