Safety Assessment on Serious Adverse Events of Targeted Therapeutic Agents Prescribed for RAS Wild-Type Metastatic Colorectal Cancer: Systematic Review and Network Meta-Analysis

Choi, Yeo Jin; Choi, Chang-Young; Rhie, Sandy Jeong; Shin, Sug Kyun

doi:10.3390/ijerph19159196

Cited by 3 publications

(3 citation statements)

References 51 publications

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“…After surgery, chemotherapy can be administered to kill any remaining cancer cells and reduce the risk of cancer recurrence. The National Comprehensive Cancer Network (NCCN) guidelines recommend the use of chemotherapy regimens, including CAPOX (capecitabine and oxaliplatin), FOLFIRI (folinic acid, fluorouracil, and irinotecan), FOLFOX (folinic acid, fluorouracil, and oxaliplatin), or FOLFOXIRI (folinic acid, fluorouracil, oxaliplatin, and irinotecan), for unresectable metastatic CRC [77]. The most commonly used chemotherapeutic regimens for CRC are FOLFOX and FOLFIRI [78].…”

Section: Clinical Status Of Irinotecan Combination Therapy In Crcmentioning

confidence: 99%

Recent Developments in Combination Chemotherapy for Colorectal and Breast Cancers with Topoisomerase Inhibitors

Jang

Kim

2023

IJMS

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DNA topoisomerases are important enzymes that stabilize DNA supercoiling and resolve entanglements. There are two main types of topoisomerases in all cells: type I, which causes single-stranded DNA breaks, and type II, which cuts double-stranded DNA. Topoisomerase activity is particularly increased in rapidly dividing cells, such as cancer cells. Topoisomerase inhibitors have been an effective chemotherapeutic option for the treatment of several cancers. In addition, combination cancer therapy with topoisomerase inhibitors may increase therapeutic efficacy and decrease resistance or side effects. Topoisomerase inhibitors are currently being used worldwide, including in the United States, and clinical trials on the combination of topoisomerase inhibitors with other drugs are currently underway. The primary objective of this review was to comprehensively analyze the current clinical landscape concerning the combined application of irinotecan, an extensively investigated type I topoisomerase inhibitor for colorectal cancer, and doxorubicin, an extensively researched type II topoisomerase inhibitor for breast cancer, while presenting a novel approach for cancer therapy.

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Section: Clinical Status Of Irinotecan Combination Therapy In Crcmentioning

confidence: 99%

Recent Developments in Combination Chemotherapy for Colorectal and Breast Cancers with Topoisomerase Inhibitors

Jang

Kim

2023

IJMS

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“…The results of this study showed no difference in the incidence of thromboembolism (ATE or VTE) between VEGF and EGFR inhibitors, and no difference in the time to thromboembolism, suggesting that the risk of thromboembolism is similar between molecular-targeted therapies. Recently, it has been reported that panitumumab-based chemotherapy is associated with an increased incidence of serious thromboembolism compared to bevacizumab-based chemotherapy [ 18 ]. In this study, the overall incidence of thromboembolism was twice as high in the EGFR inhibitor group, but the possibility of a beta error cannot be ruled out due to the limited number of cases.…”

Section: Main Textmentioning

confidence: 99%

Risk factors for thromboembolism during first-line treatment of patients with unresectable advanced or recurrent colorectal cancer: a retrospective short study

Takada

Fujiwara

Maki

et al. 2023

J Pharm Health Care Sci

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Background While cancer is a risk factor for developing thromboembolism, so is the use of molecularly targeted therapies. This study aimed to determine whether thromboembolism incidence differed between vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) inhibitor use in patients with unresectable advanced or recurrent colorectal cancer, and to compare the risk of thromboembolism caused by cancer and the use of molecular targeted therapy drugs. Main body We retrospectively evaluated patients with unresectable advanced or recurrent colorectal cancer who were treated with a cytotoxic anticancer drug and a VEGF or EGFR inhibitor combination between April 2016 and October 2021. Patients were compared in terms of the regimen administered, thromboembolism occurrence during the first-line treatment period, patient background, and clinical laboratory values. Of the 179 included patients, 12 of 134 (8.9%) in the VEGF-inhibitor group and 8 of 45 (17.8%) in the EGFR-inhibitor group developed thromboembolism, with no significant difference between the groups (P = 0.11). There was no significant difference in time to thromboembolism between patients in the VEGF- inhibitor group and patients in the EGFR-inhibitor group (P = 0.206). The cutoff value determined by a receiver operating characteristic analysis for the occurrence of thromboembolism was one point. Multivariate analysis using the occurrence of thromboembolism as the response variable identified at least one risk factor for thromboembolism (odds ratio = 4.17, P = 0.006, 95% confidence interval = 1.51–11.50). Molecular targeted therapies were not identified as a risk factor. Conclusions Although the small sample size, there was no difference in the incidence of thromboembolism between the two molecular-targeted therapies in first-line treatment of patients with unresectable advanced or recurrent colorectal cancer. Our results suggest that risk factors for thromboembolism may be more strongly influenced by cancer itself than by the use of molecularly targeted therapies.

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“…Real-world data highlight the complexity of treating RAS-positive CRC, demonstrating that patients with RAS-mutant CRC have a median overall survival ranging from 20 to 30 months when treated with current standard systemic therapies, compared to longer survival in those with RAS wild-type tumors [23]. Furthermore, the adverse effects associated with systemic treatments, including chemotherapy-induced neuropathy and the dermatological toxicities from targeted therapies, can significantly impair patients' quality of life [24,25].…”

Section: Introductionmentioning

confidence: 99%

Impact of Systemic Treatments on Outcomes and Quality of Life in Patients with RAS-Positive Stage IV Colorectal Cancer: A Systematic Review

Braicu,

Stelian,

Fulger

et al. 2024

Diseases

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This systematic review critically evaluates the impact of systemic treatments on outcomes and quality of life (QoL) in patients with RAS-positive stage IV colorectal cancer, with studies published up to December 2023 across PubMed, Scopus, and Web of Science. From an initial pool of 1345 articles, 11 relevant studies were selected for inclusion, encompassing a diverse range of systemic treatments, including panitumumab combined with FOLFOX4 and FOLFIRI, irinotecan paired with panitumumab, regorafenib followed by cetuximab ± irinotecan and vice versa, and panitumumab as a maintenance therapy post-induction. Patient demographics predominantly included middle-aged to elderly individuals, with a slight male predominance. Racial composition, where reported, showed a majority of Caucasian participants, highlighting the need for broader demographic inclusivity in future research. Key findings revealed that the addition of panitumumab to chemotherapy (FOLFOX4 or FOLFIRI) did not significantly compromise QoL while notably improving disease-free survival, with baseline EQ-5D HSI mean scores ranging from 0.76 to 0.78 and VAS mean scores from 70.1 to 74.1. Improvements in FACT-C scores and EQ-5D Index scores particularly favored panitumumab plus best supportive care in KRAS wild-type mCRC, with early dropout rates of 38–42% for panitumumab + BSC. Notably, cetuximab + FOLFIRI was associated with a median survival of 25.7 months versus 16.4 months for FOLFIRI alone, emphasizing the potential benefits of integrating targeted therapies with chemotherapy. In conclusion, the review underscores the significant impact of systemic treatments, particularly targeted therapies and their combinations with chemotherapy, on survival outcomes and QoL in patients with RAS-positive stage IV colorectal cancer, and the need for personalized treatment.

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Safety Assessment on Serious Adverse Events of Targeted Therapeutic Agents Prescribed for RAS Wild-Type Metastatic Colorectal Cancer: Systematic Review and Network Meta-Analysis

Cited by 3 publications

References 51 publications

Recent Developments in Combination Chemotherapy for Colorectal and Breast Cancers with Topoisomerase Inhibitors

Recent Developments in Combination Chemotherapy for Colorectal and Breast Cancers with Topoisomerase Inhibitors

Risk factors for thromboembolism during first-line treatment of patients with unresectable advanced or recurrent colorectal cancer: a retrospective short study

Impact of Systemic Treatments on Outcomes and Quality of Life in Patients with RAS-Positive Stage IV Colorectal Cancer: A Systematic Review

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