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

Kawai, Shinya; Takeshima, Nozomi; Hayasaka, Yu; Notsu, Akifumi; Yamazaki, Mutsumi; Kawabata, Takanori; Yamazaki, Kentaro; Mori, Keita; Yasui, Hirofumi

doi:10.1186/s12885-021-07823-7

Cited by 28 publications

(20 citation statements)

References 46 publications

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“…When comparing first-line therapies combined with bevacizumab, the group of patients treated with irinotecan-based chemotherapy had better median OS as compared to the oxaliplatin group (24 vs. 21 months respectively). However, these findings were not statistically significant and are consistent with Kawai’s recent meta-analysis that demonstrated that these two regimens are similar in terms of OS [ 20 ]. Notably, we found that patients who received more administrations of bevacizumab experienced longer OS.…”

Section: Discussionsupporting

confidence: 78%

Bevacizumab in metastatic colorectal cancer in a real-life setting – toxicity profile, survival outcomes, and impact of tumor sidedness

Chibani¹,

Bairi²,

Jarroudi³

et al. 2022

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Introduction Targeting angiogenesis in metastatic colorectal cancer (mCRC) using bevacizumab is a standard of care. The addition of this targeted biological agent to first-line infusional fluoropyrimidine-based chemotherapy was associated with superior overall survival (OS) in several randomized and controlled studies for CRC patients in the metastatic setting. However, access to this therapy in countries with limited resources is challenging. In Morocco, bevacizumab was introduced for this indication after considerable efforts of the Ministry of Health and Lalla Salma Foundation to support cancer patients with a limited income. In this report, the real-world efficacy and safety of the combination of bevacizumab with chemotherapy in mCRC are reported based on a retrospective cohort in Eastern Morocco. Material and methods The archives of the medical records of 98 mCRC patients treated with first-line bevacizumab at the Hassan II Regional Cancer Center (Oujda, Morocco) were sampled from 1 st January 2014 to 31 st December 2019 and analyzed using descriptive statistics, Kaplan-Meier estimation, and a multivariable Cox regression model for a time-to-event study. Results The toxicity profile was dominated by grade I–II proteinuria (10%), bleeding events (10%), thromboembolic events (9%), grade I–III hypertension (3%), and other rare events such as delayed healing of the stoma, scar dehiscence, intestinal perforation, and heart failure deterioration. In terms of survival, median OS and progression-free survival in the whole cohort were 22 and 13 months respectively. Patients who benefited from a metastasectomy after bevacizumab treatment had 31 months of median OS as compared to 14 months in the matched cohort with non-resectable liver metastasis. Notably, we demonstrated that tumor sidedness is a predictive factor of OS [hazard ratio (HR) = 2.452; 95% CI: 1.434–4.191, p = 0.001]. Moreover, the median OS for patients who received between 10 and 20 or more than 20 bevacizumab administrations was 24 and 33 months respectively as compared to those who received less than 10 cures (17 months) (log rank p < 0.0001). These markedly improved outcomes were also confirmed in multivariate Cox regression. A highly significant association of bevacizumab use and OS was found after adjusting for covariates (HR = 0.518, 95% CI: 0.374–0.717; p < 0.0001). Conclusions The current study confirmed the important place of this therapeutic strategy in mCRC. Additional studies with prospective enrollment are awaited to validate these findings.

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Section: Discussionsupporting

confidence: 78%

Bevacizumab in metastatic colorectal cancer in a real-life setting – toxicity profile, survival outcomes, and impact of tumor sidedness

Chibani¹,

Bairi²,

Jarroudi³

et al. 2022

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“…However, this group included patients with poor performance status and the treatment was given as a salvage regimen. On the other hand, there was no difference in PFS between FOLFIRI and FOLFOX, comparable to the literature 12 …”

Section: Discussionsupporting

confidence: 89%

The effect of primary tumour resection on patients with synchronous metastatic colorectal cancer treated with cetuximab‐containing regimens

Sertesen

Yekedüz

Köksoy

et al. 2022

ANZ Journal of Surgery

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Background: This study aims to assess the effect of primary tumour resection (PTR) on patients with metastatic colorectal cancer (mCRC) treated with cetuximab. Methods: This retrospective cohort study was conducted in a tertiary cancer center in Turkey. Patients with mCRC between January 2009 and December 2020 were extracted from the electronic hospital management system. Patients with RAS wild-type synchronous metastatic left-sided colon or rectum cancer who had cetuximab-containing treatment protocol were included in the study. The primary outcomes were overall survival (OS) and progression-free survival (PFS). The secondary outcome was response rates. Results: A total of 111 patients with mCRC were included in this study. PTR was performed in 57.7% of all patients. Fifty-nine (53.2%) and 52 (46.8%) patients had rectal and left colon tumours, respectively. The combination treatment with cetuximab was FOLFIRI in 62.2% and FOLFOX in 29.7% of all patients. In subgroup analysis, the median PFS was 7.9 and 9 months in PTR (+) and PTR (À) patients, respectively. The difference between the groups was not statistically significant (P = 0.3). The median OS was 33 months in all patients. In subgroup analysis, the median OS was 39 and 27.9 months in PTR (+) and PTR (À) patients, respectively. The difference between the groups was statistically significant (P = 0.002). After adjusting for confounding factors, PTR and ECOG performance score were the independent prognostic factors for OS. Conclusion: PTR improved the OS in patients with RAS wild-type synchronous left-sided colon or rectum cancer treated with cetuximab-containing chemotherapy regimens.

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“…Mutations in UGT genes in the tumor that reduce the glucuronidation of anticancer drugs can increase intratumoral drug concentrations, thus potentially enhancing therapy efficacy and inhibiting tumor growth. For example, irinotecan is commonly used for treating colorectal cancer (COAD), and its active metabolite, SN-38, is primarily glucuronidated by UGT1A1 with weak activity from all other UGT1As except UGT1A4 [ 101 , 102 , 103 , 104 , 105 ]. We recently showed the expression of all nine UGT1As at varying levels in COAD tumors, suggesting that there is in situ glucuronidation of SN-38 within the tumor [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

The Somatic Mutation Landscape of UDP-Glycosyltransferase (UGT) Genes in Human Cancers

Marri

Hulin

et al. 2022

Cancers

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The human UDP-glycosyltransferase (UGTs) superfamily has a critical role in the metabolism of anticancer drugs and numerous pro/anti-cancer molecules (e.g., steroids, lipids, fatty acids, bile acids and carcinogens). Recent studies have shown wide and abundant expression of UGT genes in human cancers. However, the extent to which UGT genes acquire somatic mutations within tumors remains to be systematically investigated. In the present study, our comprehensive analysis of the somatic mutation profiles of 10,069 tumors from 33 different TCGA cancer types identified 3427 somatic mutations in UGT genes. Overall, nearly 18% (1802/10,069) of the assessed tumors had mutations in UGT genes with huge variations in mutation frequency across different cancer types, ranging from over 25% in five cancers (COAD, LUAD, LUSC, SKCM and UCSC) to less than 5% in eight cancers (LAML, MESO, PCPG, PAAD, PRAD, TGCT, THYM and UVM). All 22 UGT genes showed somatic mutations in tumors, with UGT2B4, UGT3A1 and UGT3A2 showing the largest number of mutations (289, 307 and 255 mutations, respectively). Nearly 65% (2260/3427) of the mutations were missense, frame-shift and nonsense mutations that have been predicted to code for variant UGT proteins. Furthermore, about 10% (362/3427) of the mutations occurred in non-coding regions (5′ UTR, 3′ UTR and splice sites) that may be able to alter the efficiency of translation initiation, miRNA regulation or the splicing of UGT transcripts. In conclusion, our data show widespread somatic mutations of UGT genes in human cancers that may affect the capacity of cancer cells to metabolize anticancer drugs and endobiotics that control pro/anti-cancer signaling pathways. This highlights their potential utility as biomarkers for predicting therapeutic efficacy and clinical outcomes.

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

Cited by 28 publications

References 46 publications

Bevacizumab in metastatic colorectal cancer in a real-life setting – toxicity profile, survival outcomes, and impact of tumor sidedness

Bevacizumab in metastatic colorectal cancer in a real-life setting – toxicity profile, survival outcomes, and impact of tumor sidedness

The effect of primary tumour resection on patients with synchronous metastatic colorectal cancer treated with cetuximab‐containing regimens

The Somatic Mutation Landscape of UDP-Glycosyltransferase (UGT) Genes in Human Cancers

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