Comparative survival and toxicity profiles of oxaliplatin-based adjuvant regimens in stage II–III colorectal cancer: a retrospective dual-institution study

Year 2026, Volume: 9 Issue: 2, 519 - 529, 12.03.2026

Neslihan Özyurt

https://doi.org/10.32322/jhsm.1840576

https://izlik.org/JA96KP34EY

Abstract

Aims: Oxaliplatin-based chemotherapy is the standard adjuvant treatment for patients with stage III and high-risk stage II colorectal cancer (CRC). However, real-world data comparing the survival outcomes and toxicity profiles of commonly used regimens remain limited. To evaluate and compare the efficacy and tolerability of adjuvant FOLFOX, FLOX, and XELOX regimens in patients with resected stage III and high-risk stage II CRC treated in routine clinical practice.
Methods: Patients with resected stage III and high-risk stage II CRC treated with adjuvant oxaliplatin-based chemotherapy at two tertiary centers between 1998 and 2025 were retrospectively screened. A total of 180 eligible patients were included. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared with the log-rank test. Multivariable Cox proportional hazards models were used to adjust for potential confounders. Treatment-related toxicities were graded according to CTCAE criteria.
Results: Among 180 patients, the median DFS and OS for the entire cohort were 3.78 and 5.53 years, respectively. Median DFS estimates varied numerically across chemotherapy regimens, whereas median OS values were broadly comparable. Kaplan Meier log-rank analyses did not demonstrate statistically significant differences in DFS or OS between treatment groups. In multivariable Cox proportional hazards models adjusted for baseline clinical factors and treatment duration, chemotherapy regimen was not independently associated with OS. For DFS, however, the XELOX regimen was associated with a lower risk of recurrence compared with FOLFOX-6 (HR 0.51, 95% CI 0.28–0.94; p=0.031). Toxicity profiles varied significantly between regimens. Hematologic toxicities were more frequent with FOLFOX-6 and XELOX, whereas FOLFOX-4 showed comparatively lower rates of myelosuppression. Peripheral neuropathy was predominantly observed in the FOLFOX-6 and XELOX groups.
Conclusion: Oxaliplatin-based adjuvant chemotherapy regimens achieved broadly comparable long-term survival outcomes in patients with stage III and high-risk stage II CRC. After adjustment for baseline characteristics, no regimen demonstrated a clear independent OS advantage. XELOX was associated with a modest DFS benefit without a corresponding improvement in OS. Toxicity profiles differed across regimens, particularly with respect to hematologic adverse events and peripheral neuropathy. Therefore, regimen selection in routine clinical practice should balance efficacy with patient-specific tolerability and comorbidity considerations.

Keywords

Colorectal cancer , adjuvant chemotherapy , oxaliplatin-based regimens , disease-free survival , overall survival , treatment toxicity

Ethical Statement

This study was conducted in accordance with institutional ethical standards. (07.11.2025-2025/378)

Supporting Institution

The author received no financial support for the research, authorship, and/or publication of this article.

Thanks

I would like to express my appreciation to my thesis advisor Prof Dr Uğur Coşkun for providing the initial academic framework during the thesis period.

Evre II-III kolorektal kanserinde oksaliplatin bazlı adjuvan tedavi rejimlerinin karşılaştırmalı sağkalım ve toksisite profilleri: iki merkezli retrospektif bir çalışma

https://izlik.org/JA96KP34EY

Abstract

Arka Plan:
Oksaliplatin temelli kemoterapi, evre II–III kolorektal kanser (KRK) hastaları için standart adjuvan tedavidir. Ancak, yaygın olarak kullanılan rejimlerin sağkalım sonuçlarını ve toksisite profillerini karşılaştıran gerçek yaşam verileri sınırlıdır.

Amaçlar:
Rutin klinik pratiğinde tedavi edilen evre II–III CRC hastalarında adjuvan FOLFOX, FLOX ve XELOX rejimlerinin etkinlik ve tolerabilitesini değerlendirmek ve karşılaştırmak.

Yöntemler:
Gazi Üniversitesi Tıp Fakültesi’nde Ocak 1998–Aralık 2009 ve Ordu Üniversitesi Eğitim ve Araştırma Hastanesi’nde Ocak 2009–Şubat 2025 tarihleri arasında tedavi edilen hastalar uygunluk açısından tarandı. Dahil edilme kriterlerini karşılayan toplam 180 hasta çalışmaya alındı. Gazi Üniversitesi’nden elde edilen 80 hastalık özgün tez veri seti, istatistiksel gücü ve temsil edilebilirliği artırmak amacıyla Ordu Üniversitesi’nden eklenen 100 hasta ile genişletildi. Progressyonsuz sağkalım (PFS) ve genel sağkalım (OS) Kaplan–Meier yöntemiyle analiz edildi ve log-rank testi ile karşılaştırıldı. Toksisite profilleri CTCAE kriterlerine göre değerlendirildi.

Bulgular:
Tüm kohort için medyan progressyonsuz sağkalım (PFS) 3,78 yıl, medyan genel sağkalım (OS) ise 5,53 yıl olarak bulundu. Rejimler arasında PFS açısından anlamlı bir fark yoktu (p = 0.456). Buna karşın, OS anlamlı olarak farklıydı ve XELOX rejimi sağkalım açısından üstünlük gösterdi (p = 0.045). Hematolojik toksisiteler—özellikle nötropeni ve trombositopeni—en sık FOLFOX-4 rejiminde görüldü; periferik nöropati de bu grupta daha belirgindi. FLOX ise nispeten daha elverişli bir hematolojik güvenlik profiline sahipti.

Sonuçlar:
Oksaliplatin temelli adjuvan rejimler, evre II–III KRK hastalarında anlamlı uzun dönem sağkalım sağlamaktadır. Rejimler arasında PFS sonuçları benzer olmakla birlikte, XELOX rejimi daha iyi OS ile ilişkilidir ve toksisite paternleri belirgin şekilde farklılık göstermektedir. Bu nedenle, rejim seçimi yapılırken hem onkolojik etkinlik hem de hastaya özgü toksisite riskleri dikkate alınmalıdır.

Keywords

Kolorektal Neoplaziler , Kemoterapi , Adjuvan , Oksaliplatin , sağkalım Oranı , İlaç İlişkili Yan Etkiler

Ethical Statement

Bu çalışma, kurumun etik standartlarına uygun olarak yürütülmüştür. (07.11.2025-2025/378)

Supporting Institution

Yazar, bu makalenin araştırma, yazım ve/veya yayınlanması için herhangi bir mali destek almamıştır.

Thanks

Tez çalışmam süresince bana ilk akademik çerçeveyi sağlayan tez danışmanım Prof. Dr. Uğur Coşkun'a teşekkürlerimi sunmak isterim.

References

• Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. doi:10.3322/caac.21492
• Sakorafas GH, Zouros E, Peros G. Applied vascular anatomy of the colon and rectum: clinical implications for the surgical oncologist. Surg Oncol. 2006;15(4):243-255. doi:10.1016/j.suronc.2007.03.002
• Taieb J, Gallois C. Adjuvant chemotherapy for stage III colon cancer. Cancers. 2020;12(9):2679. doi:10.3390/cancers12092679
• Ishibe A, Watanabe J, Suwa Y, et al. A prospective, single-arm, multicenter trial of diverting stoma followed by neoadjuvant chemotherapy using mFOLFOX6 for obstructive colon cancer: YCOG 1305 (PROBE study). Ann Surg. 2022;276(1):140-145. doi:10.1097/SLA.0000000000004494
• André T, Boni C, Navarro M, et al. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol. 2009;27(19):3109-3116. doi:10.1200/JCO.2008.20.6771
• Yothers G, O'Connell MJ, Allegra CJ, et al. Oxaliplatin as adjuvant therapy for colon cancer: updated results of NSABP C-07 trial, including survival and subset analyses. J Clin Oncol. 2011;29(28):3768-3774. doi:10.1200/JCO.2011.36.4539
• Cheng J, Shuai X, Gao J, Wang G, Tao K, Cai K. Comparative efficacy and tolerability of adjuvant systemic treatments against resectable colon cancer: a network meta-analysis. Ther Adv Med Oncol. 2020;12: 1758835920974195. doi:10.1177/1758835920974195
• Huang WK, Hsu HC, Chang SH, et al. Real-world effectiveness of adjuvant oxaliplatin chemotherapy in stage III colon cancer: a controlled interrupted time series analysis. Front Pharmacol. 2021;12:693009. doi: 10.3389/fphar.2021.693009
• Kidwell KM, Yothers G, Ganz PA, et al. Long-term neurotoxicity effects of oxaliplatin added to fluorouracil and leucovorin as adjuvant therapy for colon cancer: results from National Surgical Adjuvant Breast and Bowel Project trials C-07 and LTS-01. Cancer. 2012;118(22):5614-5622. doi:10.1002/cncr.27593
• Park SB, Lin CS, Krishnan AV, Goldstein D, Friedlander ML, Kiernan MC. Long-term neuropathy after oxaliplatin treatment: challenging the dictum of reversibility. Oncologist. 2011;16(5):708-716. doi:10.1634/theoncologist.2010-0248
• Tournigand C, André T, Bonnetain F, et al. Adjuvant therapy with fluorouracil and oxaliplatin in stage II and elderly patients (between ages 70 and 75 years) with colon cancer: subgroup analyses of the Multicenter International Study of Oxaliplatin, Fluorouracil, and Leucovorin in the Adjuvant Treatment of Colon Cancer trial. J Clin Oncol. 2012;30(27):3353-3360. doi:10.1200/JCO.2012.42.5645
• McCleary NJ, Meyerhardt JA, Green E, et al. Impact of age on the efficacy of newer adjuvant therapies in patients with stage II/III colon cancer: findings from the ACCENT database. J Clin Oncol. 2013;31(20):2600-2606. doi:10.1200/JCO.2013.49.6638
• Nitsche U, Stöss C, Friess H. Effect of adjuvant chemotherapy on elderly colorectal cancer patients: lack of evidence. Gastrointest Tumors. 2017; 4(1-2):11-19. doi:10.1159/000479318
• Bong JW, Lee H, Jeong S, Kang S. Older age threshold for oxaliplatin benefit in stage II to III colorectal cancer. JAMA Netw Open. 2025;8(8): e2525660. doi:10.1001/jamanetworkopen.2025.25660
• Glimelius B, Osterman E. Adjuvant chemotherapy in elderly colorectal cancer patients. Cancers. 2020;12(8):2289. doi:10.3390/cancers12082289
• Kuebler JP, Wieand HS, O'Connell MJ, et al. Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol. 2007;25(16):2198-2204. doi:10.1200/JCO.2006.08.2974
• Cienfuegos J, Martínez P, Baixauli J, et al. Perineural invasion is a major prognostic and predictive factor of response to adjuvant chemotherapy in stage I–II colon cancer. Ann Surg Oncol. 2017;24(4):1077-1084. doi:10. 1245/s10434-016-5561-0
• Huang B, Feng Y, Zhu L, Xu T, Huang L, Cai G. Smaller tumor size is associated with poor survival in stage II colon cancer: an analysis of 7,719 patients in the SEER database. Int J Surg. 2016;33 Pt A:157-163. doi: 10.1016/j.ijsu.2016.07.073
• Kubicka S. Capecitabine plus oxaliplatin compared with fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: final results of the NO16968 randomized controlled phase III trial. Strahlenther Onkol. 2016;192(7):505-506. doi:10.1007/s00066-016-0991-y
• Krishnan T, Leung E, Solar Vasconcelos JP, et al. Three versus six months of adjuvant oxaliplatin-containing chemotherapy for patients with stage III colorectal cancer: a contemporary real-world analysis. JCO Oncol Pract. 2025;21(3):365-372. doi:10.1200/OP-24-00492
• Chowdhury D, Pond GR, Goffin JR. CAPOX vs. FOLFOX for colorectal cancer—real world outcomes in Ontario, Canada. Curr Oncol. 2025; 32(8):435. doi:10.3390/curroncol32080435
• Franken IA, van der Baan FH, Vink GR, et al. Survival and patient-reported outcomes of real-world high-risk stage II and stage III colon cancer patients after reduction of adjuvant CAPOX duration from 6 to 3 months. Eur J Cancer. 2024;208:114207. doi:10.1016/j.ejca.2024.114207
• Webster-Clark M, Keil AP, Robert N, et al. Comparing trial and real-world adjuvant oxaliplatin delivery in patients with stage III colon cancer using a longitudinal cumulative dose. JAMA Oncol. doi:10.1001/jamaoncol.2022.4445
• Boyle JM, Kuryba A, Cowling TE, et al. Survival outcomes associated with completion of adjuvant oxaliplatin-based chemotherapy for stage III colon cancer: a national population-based study. Int J Cancer. 2022; 150(2):335-346. doi:10.1002/ijc.33806
• Ueno H, Ishiguro M, Nakatani E, et al. Prospective multicenter study on the prognostic and predictive impact of tumor budding in stage II colon cancer: results from the SACURA trial. J Clin Oncol. 2019;37(22):1886-1894. doi:10.1200/JCO.18.02059
• Ribic CM, Sargent DJ, Moore MJ, et al. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med. 2003;349(3):247-257. doi: 10.1056/NEJMoa022289
• Roth AD, Tejpar S, Delorenzi M, et al. Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial. J Clin Oncol. 2010;28(3):466-474. doi:10.1200/JCO.2009.23.3452
• Kim GP, Colangelo LH, Wieand HS, et al. Prognostic and predictive roles of high-degree microsatellite instability in colon cancer: a National Cancer Institute–National Surgical Adjuvant Breast and Bowel Project Collaborative Study. J Clin Oncol. 2007;25(7):767-772. doi:10.1200/JCO. 2006.05.8172