Annals of Coloproctology

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Colorectal cancer

Effectiveness of primary tumor resection for survival after first-line cetuximab or bevacizumab in KRAS wild-type metastatic colorectal cancer treated with subsequent trifluridine/tipiracil or regorafenib: Yu-Hsun Chen, Chih-Chien Wu, Chien-Chou Su, Pei-Ting Lee, Yi-Chia Su; Ann Coloproctol. 2026;42(1):127-140. Published online February 27, 2026; DOI: https://doi.org/10.3393/ac.2025.00759.0108

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Abstract PDF: Purpose
The optimal sequencing of targeted therapies and the role of primary tumor resection (PTR) in KRAS wild-type metastatic colorectal cancer (mCRC) remain unclear. This study compared survival outcomes in patients treated with first-line cetuximab plus FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan) versus bevacizumab plus FOLFIRI, followed by second-line oxaliplatin-based chemotherapy and later-line trifluridine/tipiracil or regorafenib.
Methods
This retrospective cohort study used Taiwan’s National Health Insurance Research Database and the Taiwan Cancer Registry. Patients diagnosed with mCRC between 2013 and 2019 were included if they received first-line cetuximab or bevacizumab plus FOLFIRI, followed by later-line trifluridine/tipiracil or regorafenib. Patients were stratified by PTR status. Primary endpoints were overall survival and survival during trifluridine/tipiracil or regorafenib treatment. Secondary endpoints included time to treatment discontinuation (TTD) and TTD during trifluridine/tipiracil or regorafenib therapy. Stabilized inverse probability of treatment weighting was used for adjustment.
Results
Among 559 patients, 278 were assigned to the non-PTR group and 281 to the PTR group. In the non-PTR group, the cetuximab cohort demonstrated significantly longer survival during trifluridine/tipiracil or regorafenib therapy (6.2 months vs. 4.9 months; hazard ratio [HR], 0.72) and longer TTD1 (the interval between initiation of first-line therapy and the start of second-line chemotherapy; 11.8 months vs. 9.5 months; HR, 0.67) than the bevacizumab cohort. Survival differences between regimens were less pronounced among patients who underwent PTR.
Conclusion
First-line cetuximab plus FOLFIRI may confer a survival advantage over bevacizumab in patients with KRAS wild-type mCRC without PTR, including during later-line therapy with trifluridine/tipiracil or regorafenib, whereas bevacizumab appears to provide more consistent benefits in those with PTR.

Metastasis or chemotherapy

Comparative effectiveness of bevacizumab, cetuximab, and panitumumab for improving outcomes in metastatic colorectal cancer: a propensity overlap weighting analysis: Yi-Chia Su, Chien-Chou Su, Pei-Ting Lee, Chih-Chien Wu; Ann Coloproctol. 2025;41(5):462-472. Published online October 27, 2025; DOI: https://doi.org/10.3393/ac.2025.00059.0008

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Abstract PDF Supplementary Material: Purpose
Metastatic colorectal cancer (mCRC) remains a leading cause of cancer-related mortality despite advancements in targeted therapies. Monoclonal antibody medications—namely, bevacizumab, cetuximab, and panitumumab—are widely used in combination with chemotherapy as first-line treatments for unresectable mCRC in patients harboring wild-type KRAS tumors. However, the comparative effectiveness of these treatments in improving survival outcomes has not been clearly evaluated. This study aimed to directly compare the effectiveness of these 3 targeted therapies on survival outcomes in patients with unresectable mCRC.
Methods
In this retrospective cohort study, we utilized Taiwan’s National Health Insurance Database and Taiwan Cancer Registry to identify patients newly diagnosed with mCRC who were treated with at least 6 cycles of bevacizumab, cetuximab, or panitumumab between 2011 and 2021. Propensity score overlap weighting was applied to adjust for baseline differences, and outcomes were evaluated using Cox proportional hazards models. Additionally, subgroup analyses were performed separately for left- and right-sided tumors.
Results
Among 4,849 patients, treatment with cetuximab and panitumumab was associated with improved overall survival compared to bevacizumab, particularly in patients with left-sided tumors (adjusted hazard ratio, 0.77 and 0.75, respectively). Both cetuximab and panitumumab also showed significantly higher rates of conversion surgery, with panitumumab demonstrating the strongest effect. For right-sided tumors, however, the effectiveness of all 3 agents was limited, and no significant differences were observed in overall survival.
Conclusion
Cetuximab and panitumumab were more effective than bevacizumab at improving survival outcomes and facilitating conversion surgery in left-sided mCRC. These findings highlight the importance of tumor laterality and molecular profiling in guiding therapeutic strategies.

Metastasis or chemotherapy

Effectiveness of oxaliplatin-based second-line therapy following cetuximab+FOLFIRI or bevacizumab+FOLFIRI in KRAS wild-type metastatic colorectal cancer without primary tumor resection: Yi-Chia Su, Chien-Chou Su, Pei-Ting Lee, Chih-Chien Wu; Ann Coloproctol. 2025;41(4):319-329. Published online August 21, 2025; DOI: https://doi.org/10.3393/ac.2025.00087.0012

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Abstract PDF: Purpose
Wild-type unresectable metastatic colorectal cancer (mCRC) poses challenges for treatment optimization. Effective first-line targeted therapies are crucial for improving outcomes, particularly when combined with second-line oxaliplatin-based chemotherapies. This study examined the effects of first-line cetuximab+FOLFIRI versus bevacizumab+FOLFIRI, followed by second-line oxaliplatin-based chemotherapy, on survival among patients with KRAS wild-type mCRC without primary tumor resection (PTR).
Methods
A retrospective analysis of Taiwanese data (2013–2019) included patients with KRAS wild-type unresectable mCRC who received first-line cetuximab+FOLFIRI or bevacizumab+FOLFIRI, followed by second-line oxaliplatin-based chemotherapy. Survival outcomes—overall survival (OS) and time to treatment discontinuation (TTD)—were compared between these regimens using stabilized inverse probability of treatment weighting to adjust for potential confounders, followed by multivariate Cox proportional hazards regression analysis to account for clinical and biological variables.
Results
In patients without PTR, first-line cetuximab+FOLFIRI with second-line oxaliplatin-based chemotherapy significantly improved OS from the start dates of first- and second-line treatment compared to first-line bevacizumab+FOLFIRI with second-line oxaliplatin-based therapy, yielding adjusted hazard ratios (HRs) of 0.60 (95% confidence interval [CI], 0.46–0.78) and 0.56 (95% CI, 0.42–0.73), respectively. No significant difference in TTD was observed (HR, 0.82; 95% CI, 0.65–1.04).
Conclusion
First-line cetuximab+FOLFIRI followed by second-line oxaliplatin-based chemotherapy offers superior OS compared to bevacizumab+FOLFIRI followed by second-line oxaliplatin‑based chemotherapy in KRAS wild-type mCRC without PTR. These findings underscore the importance of personalized treatment sequencing, highlighting the need for further research to optimize mCRC management.

Invasiveness of and Drug Sensitivity to Various Anti-cancer Regimens in Five Colorectal Cancer Cell Lines.: Lee, Yoo Mi , Yoon, Yong Sik , Roh, Seon Ae , Cho, Dong Hyung , Kim, Jin Cheon; J Korean Soc Coloproctol. 2010;26(2):98-104.; DOI: https://doi.org/10.3393/jksc.2010.26.2.98

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Abstract PDF

PURPOSE
Colorectal cancer (CRC) is one of the leading causes of cancer death in South Korea. Angiogenesis has been associated with invasion and metastasis of tumors and with the secretion of various growth factors. Bevacizumab is a humanized monoclonal antibody that recognizes and blocks vascular endothelial growth factor (VEGF) and that targets integrin alphaVbeta3 and matrix metalloproteinases (MMPs) as angiogensis inhibitors. The aims of this study were identification of the mechanism of target molecules related to angiogenesis and demonstration of identifiable invasion by using chemotherapeutic regimens in vitro.
METHODS
The five colorectal cancer cell lines were treated with bevacizumab using standard or combined regimens. The expression of integrin alphaVbeta3 was detected and the investigation of apoptosis was done by using flow cytometry. The activations of MMP-2 and MMP-9 were measured by using gelatin zymography.
RESULTS
The apoptotic cell death was significantly increased for the combined regimens, especially for FOLFOX (5-FU, leucovorin, and oxaliplatin) with bevacizumab. Bevacizumab inhibited the expression of integrin alphaVbeta3 in the HT29 (59%), LoVo (67%), and SW480 (17%) cell lines, but did not in the AMC5 and the RKO cell lines. The activations of MMP-2 and MMP-9 were significantly reduced by treatment with bevacizumab in the HT29 and the LoVo cell lines. In the HT29 and the LoVo cell lines, thus, bevacizumab inhibited invasion and metastasis activity through down-regulation of integrin alphaVbeta3 and MMPs.
CONCLUSION
Our results provide biological evidence of potent angiogenic activity and indicate that angiogenesis is a complex process that involves multiple factors, including VEGF, integrin alphaVbeta3, and MMPs.

Citations

Citations to this article as recorded by

RGD peptide in cancer targeting: Benefits, challenges, solutions, and possible integrin–RGD interactions
Hossein Javid, Mahsa Akbari Oryani, Nastaran Rezagholinejad, Ali Esparham, Mahboubeh Tajaldini, Mehdi Karimi‐Shahri
Cancer Medicine.2024;[Epub] CrossRef

Controlled Clinical Trial

The Role of Targeted Therapy in the Treatment of Metastatic Colorectal Cancer.: Kim, Hyung Jin , Oh, Seong Taek; J Korean Soc Coloproctol. 2007;23(6):524-532.; DOI: https://doi.org/10.3393/jksc.2007.23.6.524

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1 Citations

Abstract PDF

Colorectal cancer is the fourth most common malignant disease in Korea. Until recently, fluorouracil was the only effective chemotherapeutic agent for colorectal cancer. But during the past decades, the Food and Drug Administration (FDA) has approved four new drugs for advanced colorectal cancer. Two of them (irinotecan and oxaliplatin) are cytotoxic drugs, whereas the other two (bevacizumab and cetuximab) are monoclonal antibodies against molecular targets. Bevacizumab, a humanized antibody directed against the vascular endothelial growth factor, has been examined in combination with chemotherapeutic agents in several clinical trials in patients with advanced colorectal cancer. According to the phase III randomized controlled clinical trial, the addition of bevacizumab to IFL (irinotecan, 5-FU, leucovorin) led to an impressive, statistically significant increase in the rate of response and prolongation in median overall survival. Recently, a statistically significant prolongation in median survival was also reported with the addition of bevacizumab to FOLFOX4 (oxaliplain, 5-FU, leucovorin) regimen in patients with advanced colorectal cancer. Cetuximab is a monoclonal antibody against the epidermal growth factor receptor. It appears to be synergistic with irinotecan, even in irinotecan-refractory tumors. The most common side effect of cetuximab is acne-like rash, and interestingly, the development and severity of it have been correlated with an increased likelihood of an objective response. In the future, additional research will be required to define the optimal selection and scheduling of available cytotoxic and biologic treatment in individually tailored therapeutic strategies.

Citations

Citations to this article as recorded by

Retrospective Analysis of Patients Treated with Cetuximab plus FOLFIRI for Previous Irinotecan-combined Chemotherapy in Metastatic Colorectal Cancer
Jae Woo Park, Sun-Mi Moon, Dae-Yong Hwang
Journal of the Korean Society of Coloproctology.2008; 24(5): 345. CrossRef

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