scholarly journals Comparison of Irinotecan and Oxaliplatin as the First-Line Therapies for Metastatic Colorectal Cancer: A Meta-analysis

2020 ◽  
Author(s):  
Sadayuki Kawai ◽  
Nozomi Takeshima ◽  
Yu Hayasaka ◽  
Akifumi Notsu ◽  
Mutsumi Yamazaki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Meta Analysis ◽  
Objective Response ◽  
Controlled Trials ◽  
Significant Heterogeneity ◽  
Cochrane Central Register ◽  
First Line ◽  
Significant Difference ◽  
High Incidence

Abstract BackgroundIrinotecan (IRI) and oxaliplatin (Ox) are standard therapeutic agents of the first-line treatments for metastatic colorectal cancer (mCRC). Previous meta-analyses of randomized controlled trials (RCTs) showed that treatment with Ox-based compared with IRI-based regimens was associated with better overall survival (OS). However, these reports did not include trials of molecular targeting agents and did not take methods for the administration of concomitant drugs, such as bolus or continuous infusion of 5-fluorouracil, into account. A systematic literature review was performed to compare the efficacy and toxicity profiles between IRI- and Ox-based regimens as the first-line treatments for mCRC.MethodsThis meta-analysis used data from the Cochrane Central Register of Controlled Trials, PubMed, and SCOPUS. The primary endpoint was OS, and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs).ResultsNineteen trials involving 4,571 patients were included in the analysis. No statistically significant difference was observed between the two groups in terms of OS, PFS, and ORR. There was no significant heterogeneity. Regarding ≥ grade 3 AEs, IRI-based regimens were associated with a high incidence of leukopenia, febrile neutropenia, and diarrhea. Moreover, there was a high incidence of thrombocytopenia and peripheral sensory neuropathy in patients who received Ox-based regimens. In a subgroup analysis, IRI combined with bevacizumab was correlated with a better PFS (HR = 0.90, 95% CI = 0.82–0.98, P = 0.02), but not with OS.ConclusionAlthough the safety profiles of IRI- and Ox-based regimens varied, their efficacy did not significantly differ. Therefore, both regimens could be used as the first-line treatments for mCRC with consideration of the patients’ condition or toxicity profiles.

scholarly journals Comparison of irinotecan and oxaliplatin as the first-line therapies for metastatic colorectal cancer: a meta-analysis

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sadayuki Kawai ◽  
Nozomi Takeshima ◽  
Yu Hayasaka ◽  
Akifumi Notsu ◽  
Mutsumi Yamazaki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Significant Heterogeneity ◽  
Cochrane Central Register ◽  
First Line ◽  
Anti Vegf ◽  
Significant Difference ◽  
High Incidence

Abstract Background Irinotecan (IRI) and oxaliplatin (Ox) are standard therapeutic agents of the first-line treatments for metastatic colorectal cancer (mCRC). Previous meta-analyses of randomized controlled trials (RCTs) showed that treatment with Ox-based compared with IRI-based regimens was associated with better overall survival (OS). However, these reports did not include trials of molecular targeting agents and did not take methods for the administration of concomitant drugs, such as bolus or continuous infusion of 5-fluorouracil, into account. A systematic literature review was performed to compare the efficacy and toxicity profiles between IRI- and Ox-based regimens as the first-line treatments for mCRC. Methods This meta-analysis used data from the Cochrane Central Register of Controlled Trials, PubMed, and SCOPUS. The primary endpoint was OS, and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). Results Nineteen trials involving 4571 patients were included in the analysis. No statistically significant difference was observed between the two groups in terms of OS, PFS, and ORR. There was no significant heterogeneity. Regarding ≥ grade 3 AEs, IRI-based regimens were associated with a high incidence of leukopenia, febrile neutropenia, and diarrhea. Moreover, there was a high incidence of thrombocytopenia and peripheral sensory neuropathy in patients who received Ox-based regimens. In a subgroup analysis, IRI combined with bevacizumab was correlated with a better PFS (HR = 0.90, 95% CI = 0.82–0.98, P = 0.02), but not with OS (pooled HR = 0.91, 95% CI = 0.80–1.03, P = 0.15). Conclusion Although the safety profiles of IRI- and Ox-based regimens varied, their efficacy did not significantly differ. The combination of anti-VEGF antibody and IRI was associated with better PFS compared with anti-VEGF antibody and Ox. Both regimens could be used as the first-line treatments for mCRC with consideration of the patients’ condition or toxicity profiles.

scholarly journals Efferent therapy in the first-line drug treatment of metastatic colorectal cancer

2018 ◽  
pp. 172-175
Author(s):  
Z. S. Kotova ◽  
T. Yu. Semiglazova ◽  
I. A. Baldueva ◽  
D. H. Latipova ◽  
D. O. Yurlov ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Drug Treatment ◽  
Metastatic Colorectal Cancer ◽  
Objective Response ◽  
First Line ◽  
Genetic Characteristics ◽  
Significant Difference ◽  
Before And After ◽  
Line Drug

The aim of this study is to analyse the efficacy of efferent therapy (hemosorption) as part of drug treatment in patients with metastatic colorectal cancer (mCRC) based on the use of standard first-line chemotherapy combined with the bevacizumab biosimilar. The study included 54 patients with histologically verified mCRC who received the first-line FOLFOX + bevacizumab therapy in combination with and without hemosorption. All patients of the FOLFOX + bevacizumab (+) hemosorption group (n = 32) received the hemosorption using Hemophoenix apparatus on Day 4 of the cycle during the first 6 cycles. A total of 182 hemosorption procedures were performed. The control group included 22 patients receiving the FOLFOX + bevacizumab regimen without hemosorption. The bevacizumab biosimilar was introduced in both groups throughout the treatment at standard doses once every 2 weeks. There was no statistically significant difference between the study groups in the main clinical, pathomorphological, molecular genetic characteristics (sex, age, ECOG status, localization of primary tumor, tumor differentiation, RAS, BRAF mutations, microsatellite instability, etc.).Blood sampling to evaluate the effect of hemosorption on the pharmacokinetics (PK) of bevacizumab biosimilar was performed during the 2nd cycle before (PK1) and after (PK2) hemosorption procedures. The bevacizumab biosimilar concentration in the blood of patients before and after hemosorption showed no statistically significant difference (p = 0,423).The use of pharmaceutical treatment in the FOLFOX + bevacizumab (+) hemosorption group contributed to the achievement of an objective response (OR) in 62% of patients (p = 0.001). Median progression-free survival (PFS) was 10 ± 0.9 months [95% CI 8.3-11.7] in the FOLFOX + bevacizumab (+) hemosorption group, and 7 ± 0.5 months [95% CI 4.4-11.6] in the FOLFOX + bevacizumab (-) hemosorption group. There was no significant difference in PFS between the groups of patients treated with FOLFOX + bevacizumab regimen with and without hemosorption (p = 0.445).There were statistically significant differences in the frequency of nausea, diarrhoea and asthenia in the FOLFOX + bevacizumab (+) hemosorption group. The analysis of the dynamics of the quality of life (QoL) level before and after treatment showed that QoL level related to health (p = 0.0001) as well as the emotional (p = 0.0001) and social (p = 0,04) functioning increased in patients receiving the FOLFOX + bevacizumab regimen in combination with hemosorption, 0,039).Thus, the addition of hemosorption to the first-line drug treatment according to the FOLFOX + bevacizumab regimen does not affect bevacizumab pharmacokinetics, increases the frequency of objective response, reduces toxicity of the therapy and improves the quality of patients’ life indicators.

scholarly journals Evaluation of Second-Line Anti-VEGF after First-Line Anti-EGFR Based Therapy in RAS Wild-Type Metastatic Colorectal Cancer: The Multicenter “SLAVE” Study

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1259
Author(s):  
Alessandro Parisi ◽  
Alessio Cortellini ◽  
Katia Cannita ◽  
Olga Venditti ◽  
Floriana Camarda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Performance Status ◽  
Objective Response ◽  
Treated Group ◽  
Line Treatment ◽  
Second Line ◽  
Wild Type ◽  
First Line ◽  
Significant Difference

Background: The optimal anti-angiogenic strategy as second-line treatment in RAS wild-type metastatic colorectal cancer (mCRC) treated with anti-EGFR (Epidermal Growth Factor Receptor) based first-line treatment is still debated. Methods: This multicenter, real-world, retrospective study is aimed at evaluating the effectiveness of second-line Bevacizumab- and Aflibercept-based treatments after an anti-EGFR based first-line regimen. Clinical outcomes measured were: objective response rate (ORR), progression free survival (PFS), overall survival (OS) and adverse events (AEs) profiles. Results: From February 2011 to October 2019, 277 consecutive mCRC patients received Bevacizumab-based (228, 82.3%) or Aflibercept-based (49, 17.7%) regimen. No significant difference was found regarding ORR. The median follow-up was 27.7 months (95%CI: 24.7–34.4). Aflibercept-treated group had a significantly shorter PFS compared to Bevacizumab-treated group (5.6 vs. 7.1 months, respectively) (HR = 1.34 (95%CI: 0.95–1.89); p = 0.0932). The median OS of the Bevacizumab-treated group and Aflibercept-treated group was 16.2 (95%CI: 15.3–18.1) and 12.7 (95%CI: 8.8–17.5) months, respectively (HR= 1.31 (95%CI: 0.89–1.93) p = 0.16). After adjusting for the key covariates (age, gender, performance status, number of metastatic sites and primary tumor side) Bevacizumab-based regimens revealed to be significantly related with a prolonged PFS (HR = 1.44 (95%CI: 1.02–2.03); p = 0.0399) compared to Aflibercept-based regimens, but not with a prolonged OS (HR = 1.47 (95%CI: 0.99–2.17); p = 0.0503). The incidence of G3/G4 VEGF inhibitors class-specific AEs was 7.5% and 26.5% in the Bevacizumab-treated group and the Aflibercept-treated group, respectively (p = 0.0001). Conclusion: Our analysis seems to reveal that Bevacizumab-based regimens have a slightly better PFS and class-specific AEs profile compared to Aflibercept-based regimen as second-line treatment of RAS wild-type mCRC patients previously treated with anti-EGFR based treatments. These results have to be taken with caution and no conclusive considerations are allowed.

scholarly journals Triplet Chemotherapy (FOLFOXIRI) Plus Bevacizumab Versus Doublet Chemotherapy (FOLFOX/FOLFIRI) Plus Bevacizumab in Conversion Therapy for Metastatic Colorectal Cancer: a Meta-Analysis

2018 ◽  
Vol 48 (5) ◽  
pp. 1870-1881 ◽  
Author(s):  
Lin Shui ◽  
Yu-Shen Wu ◽  
Huapeng Lin ◽  
Pixian Shui ◽  
Qin Sun ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Meta Analysis ◽  
Objective Response ◽  
R0 Resection ◽  
Conversion Therapy ◽  
Resection Rate ◽  
Triplet Chemotherapy ◽  
Significant Difference ◽  
Doublet Chemotherapy

Background/Aims: Conversion therapy can convert unresectable metastatic colorectal cancer (mCRC) into resectable. However, the optimal conversion regimen was not yet defined. This meta-analysis aimed to compare the efficacy and safety of the triplet chemotherapy (FOLFOXIRI) plus bevacizumab (Bev) with doublet chemotherapy (FOLFOX/FOLFIRI) plus Bev in conversion therapy. Methods: Randomized controlled trials (RCTs) from databases, including Pubmed, EMBASE, Cochrane clinical trials, clinicaltrial.gov and some conferences, were searched from the inception to November 2017. The R0 resection, objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and the incidence of adverse events were pooled with the use of hazard ratio (HR) or risk ratio (RR). Results: Four RCTs with 1013 patients were included. FOLFOXIRI plus Bev regimen significantly improved the overall R0 resection rate (RR 1.41, 95% confidence interval (CI) 1.07-1.85, I2=37%), liver R0 resection rate (RR 2.28, 95% CI 1.34-3.89, I2=0%), ORR (RR 1.20, 95% CI 1.09-1.32, I2=0%), PFS (HR 0.72, 95% CI 0.62-0.84, I2=36%) and OS (HR 0.80, 95% CI 0.66-0.97, I2=0%). There was no significant difference in any Grade≥3 adverse event (RR 1.08, 95% CI 0.99-1.17, I2=0%) between two regimens. FOLFOXIRI-Bev was associated with a higher risk of neutropenia (RR 1.77, 95% CI 1.13-2.79, I2=68%) and diarrhea (RR 1.65, 95% CI 1.17-2.32, I2=0%). Conclusions: Triplet chemotherapy plus Bev significantly improved the R0 resection rates, ORR, PFS and OS in comparison with doublet chemotherapy plus Bev in conversion therapy for mCRC patients, with a higher risk of neutropenia and diarrhea.

scholarly journals Network Meta-analysis of First-Line Systemic Treatment for Patients With Metastatic Colorectal Cancer

2021 ◽  
Vol 28 ◽  
pp. 107327482110334
Author(s):  
Shan Xu ◽  
Ali Sak ◽  
Yasin Bahadir Erol
Keyword(s):  
Colorectal Cancer ◽  
Adverse Events ◽  
Metastatic Colorectal Cancer ◽  
Meta Analysis ◽  
Random Effect Model ◽  
Treatment Strategies ◽  
Chemotherapeutic Agents ◽  
Controlled Trials ◽  
First Line ◽  
Central Registry

Purpose To assess the relative efficacy and safety of first-line systemic therapies in patients with metastatic colorectal cancer. Experimental Design A comprehensive literature review was conducted including MEDLINE, Embase, and the Cochrane Central Registry of Controlled Trials for phase II or III randomized controlled trials (RCTs) published up to and including July 15, 2019. We included RCTs in which at least 1 intervention was either chemotherapeutic agents (such as fluorouracil, irinotecan, or oxaliplatin) or antibodies targeting angiogenesis (such as bevacizumab) or agents that act on the epidermal growth factor receptor pathway (such as cetuximab and panitumumab) or studies reported at least one of the following outcomes: overall survival (OS), progression-free survival (PFS), and/or Grade 3 + adverse events (AEs). Using a random effect model, we performed a Bayesian network meta-analysis to analyze the probability of optimal therapeutic regime obtained from direct comparisons with indirect evidences. We estimated hazard ratios for OS and PFS. Results A total of 30 RCTs comprising 12,146 mCRC patients with 25 different treatment strategies were included. The triple combination FOLFOXIRI [fluorouracil, leucovorin, oxaliplatin, and irinotecan] plus bevacizumab provided significant survival benefits with improved OS over all other treatments. The network meta-analysis also indicated a significant advantage of using FOLFOXIRI plus bevacizumab in comparison to other treatment strategies for PFS. Besides, FOLFOXIRI plus bevacizumab was associated with the well-tolerated adverse events. Conclusions Our study supported the use of FOLFOXIRI plus bevacizumab as the best first-line regimen and potentially effective and safe strategy for the management of patients with mCRC.

Sequencing of different targeted therapies in management of KRAS wild-type metastatic colorectal cancer: A meta-analysis.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 679-679
Author(s):  
Jin Li ◽  
Gong Chen ◽  
Weijia Fang ◽  
Yongsong Tang
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Targeted Therapies ◽  
Meta Analysis ◽  
Objective Response ◽  
Indirect Comparison ◽  
Cochrane Library ◽  
Wild Type ◽  
Anti Vegf ◽  
Significant Difference

679 Background: First-line (1L) antiendothelial growth factor receptor (anti-EGFR) is considered suitable in metastatic colorectal cancer (mCRC) patients. As no treatment guidelines recommend target therapy sequence in mCRC, this meta-analysis determined the optimal sequence of targeted therapies in patients with KRAS wild type (WT) mCRC. Methods: PICO framework was used to retrieve relevant studies from PubMed, Embase, Cochrane Library and Google Scholar. mCRC patients treated with 1L anti-EGFR and second-line (2L) anti -VEGF were compared with 1L anti-VEGF and 2L anti-EGFR treatment (gp. A). Patients treated with 1L anti-VEGF and 2L anti-EGFR treatment were compared with anti-VEGF in 1L and 2L (gp. B). We also compared 2L and 3L anti-EGFR therapies (gp. C). Primary and secondary outcomes of overall survival (OS) and progression free survival (PFS) were presented as hazard ratio (HR) and 95% confidence intervals (95% CIs). Objective response rate (ORR) was evaluated in terms of relative risk (RR) and 95% CI. P < 0.05 was considered statistically significant. Results: We identified nine studies for this analysis including 1478 KRAS WT mCRC patients. In gp. p A (three studies; two retrospective and one post-hoc analysis; 450 patients), 1L anti-EGFR and 2L anti-VEGF treatment had a significantly higher OS (HR 0.83, 95% CI 0.53-1.32; p = 0.0022) and PFS (HR 0.85, 95% CI 0.76- 0.96; p = 0.0081) than 1L anti-VEGF and 2L anti-EGFR. Comparison in gp. B (n = 3 RCTs involving 431 mCRC KRAS WT patients) showed no significant difference in OS (HR 0.95, 95% CI 0.70- 1.29; p = 0.6897; I2 = 42.69%) and PFS (HR 1.43, 95% CI 0.83- 2.47; p = 0.1962; I2 = 81.55%) between the two lines of treatment. ORR was higher with anti-VEGF in both 1L and 2L in gp. B (RR 3.58, 95% CI 0.72- 17.85; p = 0.1191). In gp. C, indirect comparison showed similar OS with 3L and 2L anti-EGFR therapies ((3L and 2L: n = 2 studies each; HR 0.86. 95% CI 0.71-1.04; HR 0.78, 95% CI 0.51-1.20; 2L vs. 3L; p = 0.06). Conclusions: Patients with KRAS WT mCRC achieved maximum benefit with 1L anti-EGFR and 2L anti-VEGF than with 1L anti-VEGF and 2L anti-EGFR or 1L and 2L anti-VEGF. Hence, it is suggested to initiate the therapy with 1L anti-EGFR to derive the maximum clinical benefit.

Efficacy and Toxicity of Addition of Bevacizumab to Chemotherapy in Patients with Metastatic Colorectal Cancer

2019 ◽  
Vol 21 (10) ◽  
pp. 718-724 ◽  
Author(s):  
Wen-Cong Ruan ◽  
Yue-Ping Che ◽  
Li Ding ◽  
Hai-Feng Li
Keyword(s):  
Colorectal Cancer ◽  
Adverse Event ◽  
Metastatic Colorectal Cancer ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Clinical Prognosis ◽  
Line Therapy ◽  
Significant Difference

Background: Pre-treated patients with first-line treatment can be offered a second treatment with the aim of improving their poor clinical prognosis. The therapy of metastatic colorectal cancer (CRC) patients who did not respond to first-line therapy has limited treatment options. Recently, many studies have paid much attention to the efficacy of bevacizumab as an adjuvant treatment for metastatic colorectal cancer. Objectives: We aimed to evaluate the efficacy and toxicity of bevacizumab plus chemotherapy compared with bevacizumab-naive based chemotherapy as second-line treatment in people with metastatic CRC. Methods: Electronic databases were searched for eligible studies updated to March 2018. Randomized-controlled trials comparing addition of bevacizumab to chemotherapy without bevacizumab in MCRC patients were included, of which, the main interesting results were the efficacy and safety profiles of the addition of bevacizumab in patients with MCRC as second-line therapy. Result: Five trials were eligible in the meta-analysis. Patients who received the combined bevacizumab and chemotherapy treatment in MCRC as second-line therapy showed a longer overall survival (OS) (OR=0.80,95%CI=0.72-0.89, P<0.0001) and progression-free survival (PFS) (OR=0.69,95%CI=0.61-0.77, P<0.00001). In addition, there was no significant difference in objective response rate (ORR) (RR=1.36,95%CI=0.82-2.24, P=0.23) or severe adverse event (SAE) (RR=1.02,95%CI=0.88-1.19, P=0.78) between bevacizumab-based chemotherapy and bevacizumabnaive based chemotherapy. Conclusion: Our results suggest that the addition of bevacizumab to the chemotherapy therapy could be an efficient and safe treatment option for patients with metastatic colorectal cancer as second-line therapy and without increasing the risk of an adverse event.

scholarly journals Short Segment versus Long Segment Pedicle Screws Fixation in Management of Thoracolumbar Burst Fractures: Meta-Analysis

2017 ◽  
Vol 11 (1) ◽  
pp. 150-160 ◽  
Author(s):  
Tarek Ahmed Aly
Keyword(s):  
Pedicle Screw ◽  
Screw Fixation ◽  
Meta Analysis ◽  
Pedicle Screw Fixation ◽  
Risk Of Bias ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Thoracolumbar Burst Fractures ◽  
Burst Fractures ◽  
Significant Difference

<p>Posterior pedicle screw fixation has become a popular method for treating thoracolumbar burst fractures. However, it remains unclear whether additional fixation of more segments could improve clinical and radiological outcomes. This meta-analysis was performed to evaluate the effectiveness of fixation levels with pedicle screw fixation for thoracolumbar burst fractures. MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Springer, and Google Scholar were searched for relevant randomized and quasirandomized controlled trials that compared the clinical and radiological efficacy of short versus long segment for thoracolumbar burst fractures managed by posterior pedicle screw fixation. Risk of bias in included studies was assessed using the Cochrane Risk of Bias tool. Based on predefined inclusion criteria, Nine eligible trials with a total of 365 patients were included in this meta-analysis. Results were expressed as risk difference for dichotomous outcomes and standard mean difference for continuous outcomes with 95% confidence interval. Baseline characteristics were similar between the short and long segment fixation groups. No significant difference was identified between the two groups regarding radiological outcome, functional outcome, neurologic improvement, and implant failure rate. The results of this meta-analysis suggested that extension of fixation was not necessary when thoracolumbar burst fracture was treated by posterior pedicle screw fixation. More randomized controlled trials with high quality are still needed in the future.</p>

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