Annals of Coloproctology

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Original Article

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.

Case Report

Oxaliplatin-induced Pulmonary Fibrosis: Two Case Reports: Chun-Geun Ryu, Eun-Joo Jung, Gangmi Kim, Su Ran Kim, Dae-Yong Hwang; J Korean Soc Coloproctol. 2011;27(5):266-269. Published online October 31, 2011; DOI: https://doi.org/10.3393/jksc.2011.27.5.266

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8 Citations

Abstract PDF

Oxaliplatin with infusional 5-fluorouracil plus leucovorin (FOLFOX regimen) is the one of the standard chemotherapy regimens for treating a colorectal carcinoma. The most common side effects include neutropenia, diarrhea, vomiting and peripheral neuropathy, and these are moderate and manageable. However, pulmonary toxicity is rarely reported to be associated with the FOLFOX regimen. Moreover, there is no established guideline for the management of this side effect. Here, along with a literature review, we report two cases of rapidly developing pulmonary fibrosis related to the use of the FOLFOX regimen in patients with colorectal carcinomas.

Citations

Citations to this article as recorded by

The intervention of B. longum metabolites in Fnevs' carcinogenic capacity: A potential double-edged sword
Jingyu Xu, Xinyu Wu, Luyi Yang, Xiaoxi Xu
Experimental Cell Research.2025; 445(1): 114407. CrossRef
Oxaliplatin-Induced Pulmonary Fibrosis: A Rare but Fatal Reality
Kinnera Sahithi Urlapu, Dmitry Lvovsky
Cureus.2023;[Epub] CrossRef
Pulmonary Fibrosis Secondary to Oxaliplatin Treatment: From Rarity to Reality: A Case Study and Literature Review
Ana C. Moreira, João Portela, Carlos Couto, José Duarte, Natália Martins, Jorge Soares
Oncology and Therapy.2020; 8(2): 183. CrossRef
A case report of acute pulmonary hypertension after hyperthermic intraperitoneal chemotherapy (HIPEC) and review of the literature
Thomas S. Zajonz, Michael Sander, Winfried Padberg, Andreas Hecker, Ruediger Hörbelt, Christian Koch, Emmanuel Schneck
Annals of Medicine and Surgery.2018; 27: 26. CrossRef
Prognosis and treatment of FOLFOX therapy related interstitial pneumonia: a plea for multimodal immune modulating therapy in the respiratory insufficient patient
Annick De Weerdt, Amélie Dendooven, Annemie Snoeckx, Jan Pen, Martin Lammens, Philippe G. Jorens
BMC Cancer.2017;[Epub] CrossRef
Oxaliplatin-Induced Pulmonary Toxicity in Gastrointestinal Malignancies: Two Case Reports and Review of the Literature
Mor Moskovitz, Mira Wollner, Nissim Haim
Case Reports in Oncological Medicine.2015; 2015: 1. CrossRef
Pulmonary Fibrosis Secondary to FOLFOX Chemotherapy: A Case Report
Wai Cheong Soon, Kate West, David Gibeon, Elizabeth Frances Bowen
Case Reports in Oncology.2014; 7(3): 662. CrossRef
Granulomatous Lung Disease Requiring Mechanical Ventilation Induced by a Single Application of Oxaliplatin-Based Chemotherapy for Colorectal Cancer: A Case Report
Dane Wildner, Frank Boxberger, Axel Wein, Kerstin Wolff, Heinz Albrecht, Gudrun Männlein, Rolf Janka, Kerstin Amann, Jürgen Siebler, Werner Hohenberger, Markus F. Neurath, Richard Strauß
Case Reports in Oncological Medicine.2013; 2013: 1. CrossRef

Original Articles

Adjuvant Chemotherapy Using the FOLFOX Regimen in Colon Cancer: Hyeong-Joon Jeon, Jin-Hee Woo, Hak-Yoon Lee, Ki-Jae Park, Hong-Jo Choi; J Korean Soc Coloproctol. 2011;27(3):140-146. Published online June 30, 2011; DOI: https://doi.org/10.3393/jksc.2011.27.3.140

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12 Citations

Abstract PDF

Purpose

Great progress has been made in the adjuvant treatment of colon cancer. The aim of this study was to evaluate the efficacy of postoperative adjuvant chemotherapy using the FOLFOX regimen in patients with stage III and high-risk stage II colon cancer.

Methods

Eighty-two patients who underwent a potentially curative resection for stage III or high-risk stage II colon cancer were enrolled in this retrospective study. They received FOLFOX4 or modified FOLFOX6. The primary endpoint was disease-free survival.

Results

During the median follow-up of 37 months (range, 21 to 61 months), 14 patients experienced disease relapse. The disease-free survival rate at 3 years was 82.9%: 84.6% for stage II and 82.6% for stage III. At the time of the analysis, 8 patients were dead from recurrence. The probability of overall survival at 5 years was 74.5%: 90% for stage II and 74.6% for stage III. Grade 3 or 4 hematologic adverse events included neutropenia (40.2%), anemia (2.4%), and thrombocytopenia (1.2%). Gastrointestinal toxicities included grade 3 or 4 nausea (4.9%) and stomatitis (2.4%). Peripheral sensory neuropathy was observed in 81.7% of the patients during treatment. Of the 11 patients (13.4%) who had grade 3 peripheral sensory neuropathy during treatment, grade 3 symptoms were persistent in 3 patients with gait disturbance at the time of analysis. No treatment-related deaths were recorded.

Conclusion

Postoperative chemotherapy using the FOLFOX regimen, oxaliplatin in combination with 5-fluorouracil and leucovorin, is effective and tolerable in patients with stage III and high-risk stage II colon cancer.

Citations

Citations to this article as recorded by

Management of metastatic colorectal cancer: consensus in the Gulf Cooperation Council countries
Bazarbashi Shouki, Alnajjar Abdelsalam, Al Sharm Abdullah, Alshammari Kanan, Al Sherhi Ahmed, Dawoud Emad, Heinemann Volker, Aseafan Mohamed, Chehal Aref, Alghamdi Mohammed, Hamza Dina, Khoury Maroun, Venniyoor Ajit, Mahrous Mervat, Rasul Kakil, Elsamany
Therapeutic Advances in Medical Oncology.2025;[Epub] CrossRef
Cathayanon E induces apoptosis and enhances oxaliplatin sensitivity in colorectal cancer through suppression of MCL1
Liang Cen, Xin Hu, Guozhen An, Lichao Wang, Yanghao Hu, Junjie He, Hanghang Qin, Yongsen Li, Hongjuan Cui
Apoptosis.2025; 30(11-12): 2830. CrossRef
Transcriptomic and Cytogenetic Analysis of Oxaliplatin-Resistant Colorectal Adenocarcinoma HCT116 Cells to Identify Markers Associated with Platinum Resistance
Alisa Morshneva, Olga Gnedina, Ksenia Fedotova, Natalija Yartseva, Nikolay Aksenov, Maria Igotti
International Journal of Molecular Sciences.2025; 26(18): 8869. CrossRef
Neoadjuvant chemotherapy outcome with taxane-based versus non-taxane protocols in gastric cancer
Shirin Kianersi, Sina Salari, Hamid Rezvani, Mohammad A. Araskhan, Alireza Shirangi, Mohammad R. Fathi, Mahmoud D. Ghorbi
Journal of Education and Health Promotion.2023;[Epub] CrossRef
Extending the boundaries of cancer therapeutic complexity with literature text mining
Danna Niezni, Hillel Taub-Tabib, Yuval Harris, Hagit Sason, Yakir Amrusi, Dana Meron-Azagury, Maytal Avrashami, Shaked Launer-Wachs, Jon Borchardt, M. Kusold, Aryeh Tiktinsky, Tom Hope, Yoav Goldberg, Yosi Shamay
Artificial Intelligence in Medicine.2023; 145: 102681. CrossRef
Modified Folfox6 as Adjuvant Chemotherapy in Vietnamese Patients With Colorectal Cancer
T. Quang Nguyen, T. Oanh Bui, P. Thao Tran, V. Thuan Tran, V. Hieu Nguyen, Q. Hoan Chu, T. A. Tuyet Bui, N. Quynh Le, V. Quang Le, V. Tu Dao
Cancer Control.2019;[Epub] CrossRef
Operative Versus Nonoperative Management of Appendicitis: A Long-Term Cost Effectiveness Analysis
Lindsay A. Sceats, Seul Ku, Alanna Coughran, Britainy Barnes, Emily Grimm, Matthew Muffly, David A. Spain, Cindy Kin, Douglas K. Owens, Jeremy D. Goldhaber-Fiebert
MDM Policy & Practice.2019;[Epub] CrossRef
Efficacy and clinical monitoring strategies for immune checkpoint inhibitors and targeted cytokine immunotherapy for locally advanced and metastatic colorectal cancer
Shelby N. Bess, Gage J. Greening, Timothy J. Muldoon
Cytokine & Growth Factor Reviews.2019; 49: 1. CrossRef
Association of baseline patient characteristics with adjuvant chemotherapy toxicities in stage III colorectal cancer patients
Akie Watanabe, Chang Cheng Yang, Winson Y. Cheung
Medical Oncology.2018;[Epub] CrossRef
Risk Stratification in Patients with Stage II Colon Cancer
Ramzi Amri, Jonathan England, Liliana G. Bordeianou, David L. Berger
Annals of Surgical Oncology.2016; 23(12): 3907. CrossRef
Anti-Colorectal Cancer Chemotherapy-Induced Diarrhoea: Current Treatments and Side-Effects
Rachel M. McQuade, Joel C. Bornstein, Kulmira Nurgali
International Journal of Clinical Medicine.2014; 05(07): 393. CrossRef
Multiple Cancers in a Patient with Systemic Sclerosis and Aggravated Interstitial Lung Disease by Chemotherapy
Chan Kwon Park, Seok Jong Lee, Hyung Jun Cho, Kyeong Soo Lee, Sung Jun Kim, Gu Min Cho, Ha Ni Lee
Tuberculosis and Respiratory Diseases.2013; 75(3): 111. CrossRef

Change in Expression of Survivin Caused by Using Oxaliplatin in HCT116 Colon Cancer Cells: Won Jun Sohn, Jung Won Lee, Dong-Guk Park; J Korean Soc Coloproctol. 2010;26(4):246-253. Published online August 31, 2010; DOI: https://doi.org/10.3393/jksc.2010.26.4.246

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2 Citations

Abstract PDF

Purpose

Oxaliplatin is a third-generation platinum compound, and it has no nephrotoxicity and has reduced bone marrow toxicity. Cancer cells that are resistant to cisplatin are sensitive to oxaliplatin. Oxaliplatin is used widely for the treatment of colon cancers. Recently, oxaliplatin was reported to inhibit the expression of survivin, which protects cell apoptosis. However, there are no reports on the expressions of survivin variants and the changes in intracellular localization of survivin in cancer cells. We studied the expression of survivin caused by oxaliplatin in HCT116 colon cancer cells, and we observed the localization of survivin in the mitotic phase.

Methods

We treated the HCT116 colon cancer cells with 2.0 µM of oxaliplatin, and we studied the expressions of survivin protein, and survivin mRNA variants, as well as the changes in intracellular localization, by using the Western blot method, RT-PCR, immunocytochemistry, and flowcytometry.

Results

Oxaliplatin inhibits the expression of the survivin protein and survivin mRNA in HCT116 colon cancer cells. The expression of the survivin-2B variants, which have no antiapoptotic activity but control cell mitosis by localization on a microtubule, is reduced continuously 2 days after treatment with oxaliplatin. In immunocytochemistry, expression of survivin in the cytoplasm is reduced and especially is not expressed in microtubules and contractile rings.

Conclusion

One of the mechanisms of oxaliplatin is to inhibit the expression of and to change the localization of survivin. Based on these results, we suggest that changes in the expression of survivin variants and in their localization are two effects of oxaliplatin.

Citations

Citations to this article as recorded by

Combining bevacizumab and chemoradiation in rectal cancer. Translational results of the AXEBeam trial
M Verstraete, A Debucquoy, J Dekervel, J van Pelt, C Verslype, E Devos, G Chiritescu, K Dumon, A D'Hoore, O Gevaert, X Sagaert, E Van Cutsem, K Haustermans
British Journal of Cancer.2015; 112(8): 1314. CrossRef
Antichemosensitizing effect of resveratrol in cotreatment with oxaliplatin in HCT116 colon cancer cell
Dong-Guk Park
Annals of Surgical Treatment and Research.2014; 86(2): 68. CrossRef

Comparison between Responder and Non- responder of Oxaliplatin Chemotherapy for Metastatic Colorectal Cancer.: Cho, Min Mi , Bae, Ok Suk , Baek, Seong Kyu , Lee, Tae Soon , Park, Sung Dae; J Korean Soc Coloproctol. 2006;22(6):411-417.

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Abstract PDF: PURPOSE
The purpose of this study was to evaluate the clinicopathological significance of responders with metastatic colorectal cancer treated with oxaliplatin chemotherapy.
METHODS
A total of 52 patients with unresectable metastatic colorectal cancer were enrolled for treatment between March 2000 and August 2005. Patients received first line chemotherapy consisted of oxaliplatin 85 mg/m2 or 130 mg/m2 as a 2-hour infusion on day 1, concurrently with leucovorin (LV) 20 mg/m2 as a bolus infusion on day 1~5, followed by continuous infusion of 5-fluorouracil (5-FU) 425 mg/m2 on day 1~5. This treatment was repeated in 2 or 3 week intervals. All responses were assessed after 4 cycles of therapy by independent radiologic experts and categorized into two groups: responder (major reduction of tumor) and non-responder group (no change or progression of the tumor.
RESULTS
The response rate was 51.9 percent (27/52 patients). There were no significant differences in clinicopathologic parameters between two groups. The decrease of CEA value after chemotherapy was significantly more frequent in the responder group than in the non-responder group.
CONCLUSIONS
We could not find any clinical differences between the two groups, but these results suggest that oxaliplatin chemotherapy has a beneficial effect on tumor shrinkage and serum CEA value can be an indicator for tumor response of oxaliplatin in advanced colorectal cancer.

Differences of Response Rates according to Metastatic Sites after Oxaliplatin, 5- Fluorouracil, and Leucovorin Combination Chemotherapy (FOLFOX 3) in Advanced Colorectal Cancer.: Lee, Seung Hyun , Ahn, Byung Kwon , Baek, Sung Uhn; J Korean Soc Coloproctol. 2005;21(1):42-47.

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Abstract PDF: PURPOSE
Oxaliplatin is a recently developed active agent in colorectal cancer. Clinical observations have demonstrated synergistic effects of oxaliplatin with 5-fluorouracil (5- FU) and leucovorin (LV), even in 5-FU-resistant colorectal cancer. The purpose of this study was to determine response rates according to clinical factors after oxaliplatin, 5-FU and LV combination chemotherapy (FOLFOX 3) in metastatic colorectal cancer.
METHODS
We reviewed 44 patients who had received FOLFOX 3 from Jan. 2000 to Dec. 2002. The combination chemotherapy consisted of oxaliplatin (85 mg/m2 on day 1) as a 2~6 hour infusion followed by continuous infusion of 5-FU (1500 mg/m2 on day 1, 2), concurrently with LV (45 mg on day 1, 2) as a 2 hour infusion. Cycles were repeated by 2-week intervals. We compared the response rates according to clinical factors such as primary sites, cycle, tumor differentiation, metastatic sites, serum CEA, and previous chemotherapy.
RESULTS
Of the 44 patients who had received the combination chemotherapy with oxaliplatin, 5-FU, and LV, 19 cases were male, 25 cases were female. The median age was 50.7 years. The primary tumor sites were colon in 21 cases (47.7%), and rectum in 23 cases (52.3%). The metastatic sites were liver in 27 cases (61.4%), lung in 9 (20.5%), pelvis in 3, lymph node in 5, and peritoneum in 1. Thirty- five patients had received the combination chemotherapy as first line. Complete response was observed in 3 cases (6.8%). Partial response was in 7 cases (15.9%), stable disease status in 15 cases (34.1%), progressive disease status in 19 cases (43.2%), respectively. There were a no significant differences in response rates according to primary sites, tumor differentiation, serum CEA, and previous chemotherapy. However, with the metastatic sites, there were significant differences in response rates. Response rates were higher in lung (5/9), lymph node (3/4) metastases than any other metastatic sites (P <0.01).
CONCLUSIONS
The objective response rate of FOLFOX 3 was 22.7% in metastatic colorectal cancers. The only significant clinical factor was metastatic sites. The lung and lymph node metastases showed better response than metastatses to liver, pelvis, and peritoneum. To evaluate the differences of response rates according to metastatic sites, we need further study.

Clinical Trial of Oxaliplatin, 5-Fluorocuracil, and Leucovorin in Advanced Colorectal Cancer: 48 Cases.: Lee, Seung Hyun , Ahn, Byung Kwon , Baek, Sung Uhn; J Korean Soc Coloproctol. 2002;18(6):402-407.

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Abstract PDF: PURPOSE
Although 5-fluorouracil (5-FU) has been used as the basis of chemotherapy regimen for colorectal cancer for more than 40 years, 5-FU as single agent treatment has rarely achieved objective response rates higher than 15% in advanced colorectal cancers. The modulation of 5-FU with biologic modifiers has resulted in higher response rates, but survival advantages was not meaningful. Oxaliplatin is one of the newly developed drugs with proven activity against colorectal cancer. To evaluate the therapeutic efficacy and safety profile of oxaliplatin, we reviewed patients who received oxaliplatin chemotherapy.
METHODS
We reviewed 48 patients who received combination chemotherapy with oxaliplatin, 5-FU, and leucovorin (LV) from Jan. 2000 to Dec. 2001. The combination chemotherapy consisted of oxaliplatin (85 mg/m2 on day 1) as a 2~6 hour infusion followed by continuous infusion of 5-FU (1,500 mg/m2 on day 1, 2), concurrently with LV (45 mg on day 1, 2) as a 2 hour infusion. The combination chemotherapy interval was 2 weeks.
RESULTS
Of the 48 patients who received the combination chemotherapy with oxaliplatin, 5-FU, and LV, 25 cases were male, 23 cases were female. The median age was 51.4 years. The primary tumor sites were colon in 22 cases, and rectum in 26. According to TNM stage at diagnosis, 1 case was stage I, 5 cases were stage II, 21 cases were stage III, and 21 cases were stage IV. The metastatic sites were liver in 29 cases, lung in 10, pelvis in 7, peritoneum in 5, bone in 1, lymph node in 1, and spleen in 2. Previous chemotherapy were Mayo regimen in 43 patients, irrinotecan in 1 patient. Four patients had not received previous chemotherapy. Previously of the 48 patients, we could assess the chemotherapy response for 25 cases. Complete response was not observed. Partial response was 3 cases (12%), stable disease in 12 cases (48%), progressive disease in 10 cases (40%). From 227 cycles analyzed, the main toxicity was gastrointestinal one. Peripheral neuropathy was identifed in 5 cases.
CONCLUSIONS
We reviewed 48 patients with advanced colorectal cancer who received combination chemotherapy with oxaliplatin, 5-FU and LV. Of the 25 evaluable patients, the objective response rate was 12%. In our study, the combination chemotherapy with oxaliplatin, 5-FU, LV has not resulted in improved response rate, but overall toxicity was acceptable.

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