Skip to main content

Advertisement

SpringerLink
Log in

Oxaliplatin-based adjuvant chemotherapy rather than fluorouracil-based chemotherapy in rectal cancer is more efficient to decrease distant metastasis and increase survival after preoperative chemoradiotherapy and surgery: a meta-analysis

  • Original Article
  • Published:
International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

The standard treatment of stage II–III rectal cancer is preoperative chemoradiotherapy (CRT), followed by total mesorectal excision (TME). However, the rate of metastasis is still high following this treatment. Therefore, several adjuvant chemotherapy studies have been conducted on reducing subsequent metastases and increasing survival, although there are still no definite conclusions.

Methods

We searched for published prospective randomized controlled trials comparing adjuvant chemotherapy regimens following standard preoperative CRT and curative surgery in stage II–III rectal cancer. We systematically searched Medline, Embase, and the Cochrane Library for relevant trials done from January 2004 to January 2021. Review Manager (RevMan, version 5.3) was used to analyze the data.

Results

We initially searched 1955 studies. We screened and carefully selected four randomized controlled trials with 2897 patients. Compared to the 5-FU-based regimen group, the oxaliplatin-added regimen group attained a higher 3-year locoregional control rate (relative risk [RR] of 0.64, 95% confidence interval [CI], 0.48–0.86; p = 0.003) and 3-year distant metastasis control rate (RR of 0.82, 95% CI, 0.71–0.95; p = 0.007). The oxaliplatin-added regimen group had significantly increased 3-year disease-free survival with a hazard ratio (HR) of 0.85 (95% CI: 0.74–0.97, p = 0.020), but not overall survival (p = 0.740). Grade 3 or higher acute toxicity rates did not differ between the two groups (p = 0.190).

Conclusion

The addition of oxaliplatin to adjuvant therapy for stage II–III rectal cancer following preoperative CRT and TME may increase disease-free survival without significant increases in toxicity, but not overall survival.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Glynne-Jones R, Wyrwicz L, Tiret E, Brown G, Rödel C, Cervantes A, Arnold D (2018) Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 29(suppl 4):iv263

    Article  CAS  Google Scholar 

  2. Riihimäki M, Hemminki A, Sundquist J, Hemminki K (2016) Patterns of metastasis in colon and rectal cancer. Sci Rep 6:29765

    Article  Google Scholar 

  3. Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C (2012) Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol 30:1926–1933

    Article  CAS  Google Scholar 

  4. Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT (2012) Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol 13:579–588

    Article  CAS  Google Scholar 

  5. Song JH, Jeong JU, Lee JH, Kim SH, Cho HM, Um JW (2017) Preoperative chemoradiotherapy versus postoperative chemoradiotherapy for stage II-III resectable rectal cancer: a meta-analysis of randomized controlled trials. Radiat Oncol J 35:198–207

    Article  CAS  Google Scholar 

  6. André T, de Gramont A, Vernerey D, Chibaudel B, Bonnetain F, Tijeras-Raballand A (2015) Adjuvant fluorouracil, leucovorin, and oxaliplatin in stage II to III colon cancer: updated 10-year survival and outcomes according to BRAF mutation and mismatch repair status of the MOSAIC Study. J Clin Oncol 33:4176–4187

    Article  Google Scholar 

  7. Yothers G, O’Connell MJ, Allegra CJ, Kuebler JP, Colangelo LH, Petrelli NJ (2011) Oxaliplatin as adjuvant therapy for colon cancer: updated results of NSABP C-07 trial, including survival and subset analyses. J Clin Oncol 29:3768–3774

    Article  CAS  Google Scholar 

  8. Meyers BM, Cosby R, Quereshy F, Jonker D (2017) Adjuvant chemotherapy for stage II and III colon cancer following complete resection: a cancer care ontario systematic review. Clin Oncol (R Coll Radiol) 29:459–465

    Article  CAS  Google Scholar 

  9. Bregni G, Akin Telli T, Camera S, Deleporte A, Moretti L, Bali AM (2020) Adjuvant chemotherapy for rectal cancer: current evidence and recommendations for clinical practice. Cancer Treat Rev 83:101948

    Article  CAS  Google Scholar 

  10. Glimelius B (2020) Adjuvant chemotherapy in rectal cancer: state of the art and future perspectives. Curr Opin Oncol 32:377–383

    Article  Google Scholar 

  11. Hong YS, Kim SY, Lee JS, Nam BH, Kim KP, Kim JE (2019) Oxaliplatin-based adjuvant chemotherapy for rectal cancer after preoperative chemoradiotherapy (ADORE): long-term results of a randomized controlled trial. J Clin Oncol 37:3111–3123

    Article  CAS  Google Scholar 

  12. Hong YS, Nam BH, Kim KP, Kim JE, Park SJ, Park YS (2014) Oxaliplatin, fluorouracil, and leucovorin versus fluorouracil and leucovorin as adjuvant chemotherapy for locally advanced rectal cancer after preoperative chemoradiotherapy (ADORE): an open-label, multicentre, phase 2, randomised controlled trial. Lancet Oncol 15:1245–1253

    Article  CAS  Google Scholar 

  13. Rödel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D (2015) Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 16:979–989

    Article  Google Scholar 

  14. Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L (2019) Neoadjuvant modified FOLFOX6 with or without radiation versus fluorouracil plus radiation for locally advanced rectal cancer: final results of the Chinese FOWARC trial. J Clin Oncol 37:3223–3233

    Article  CAS  Google Scholar 

  15. Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L (2016) Modified FOLFOX6 with or without radiation versus fluorouracil and leucovorin with radiation in neoadjuvant treatment of locally advanced rectal cancer: initial results of the Chinese FOWARC Multicenter, Open-Label, Randomized Three-Arm Phase III Trial. J Clin Oncol 20(34):3300–3307

    Article  Google Scholar 

  16. Schmoll HJ, Stein A, Van Cutsem E, Price T, Hofheinz RD, Nordlinger B (2021) Pre- and postoperative capecitabine without or with oxaliplatin in locally advanced rectal cancer: PETACC 6 Trial by EORTC GITCG and ROG, AIO, AGITG, BGDO, and FFCD. J Clin Oncol 39:17–29

    Article  CAS  Google Scholar 

  17. André T, Boni C, Navarro M, Tabernero J, Hickish T, Topham C (2009) 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 27:3109–3116

    Article  Google Scholar 

  18. Kuebler JP, Wieand HS, O’Connell MJ, Smith RE, Colangelo LH, Yothers G (2007) 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 25:2198–2204

    Article  CAS  Google Scholar 

  19. Enríquez-Navascués JM, Borda N, Lizerazu A, Placer C, Elosegui JL, Ciria JP (2011) Patterns of local recurrence in rectal cancer after a multidisciplinary approach. World J Gastroenterol 17:1674–1684

    Article  Google Scholar 

  20. Wewala NT, Jameson MB (2017) The Role of Oxaliplatin in Chemoradiotherapy for Rectal Cancer. Asia Pac J Clin Oncol 13:341–342

    Article  Google Scholar 

  21. Gérard JP, Azria D, Gourgou-Bourgade S, Martel-Lafay I, Hennequin C, Etienne PL (2012) Clinical outcome of the ACCORD 12/0405 PRODIGE 2 randomized trial in rectal cancer. J Clin Oncol 30:4558–4565

    Article  Google Scholar 

  22. Aschele C, Cionini L, Lonardi S, Pinto C, Cordio S, Rosati G (2011) Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer: pathologic results of the STAR-01 randomized phase III trial. J Clin Oncol 29:2773–2780

    Article  CAS  Google Scholar 

  23. Thavaneswaran S, Kok PS, Price T (2017) Evaluating the addition of oxaliplatin to single agent fluoropyrimidine in the treatment of locally advanced rectal cancer: a systematic review and meta-analysis. Expert Rev Anticancer Ther 17:965–979

    Article  CAS  Google Scholar 

  24. NCCN guideline, Rectal Cancer (version 2.2021). Available from: http://www.nccn.org/professionals/physician_gls/pdf/rectal.pdf. Accessed date 15 Sept 2021

  25. Haller DG (2000) Safety of oxaliplatin in the treatment of colorectal cancer. Oncology (Williston Park) 14(12 Suppl 11):15–20

    CAS  Google Scholar 

  26. Bananzadeh A, Hafezi AA, Nguyen N, Omidvari S, Mosalaei A, Ahmadloo N, Ansari M, Mohammadianpanah M (2021) Efficacy and safety of sequential neoadjuvant chemotherapy and short-course radiation therapy followed by delayed surgery in locally advanced rectal cancer: a single-arm phase II clinical trial with subgroup analysis between the older and young patients. Radiat Oncol J 39:270–278

    Article  Google Scholar 

  27. Zheng J, Feng X, Hu W, Wang J, Li Y (2017) Systematic review and meta-analysis of preoperative chemoradiotherapy with or without oxaliplatin in locally advanced rectal cancer. Medicine 96:e6487

    Article  Google Scholar 

  28. Yang YJ, Cao L, Li ZW, Zhao L, Wu HF, Yue D, Yang JL, Zhou ZR, Liu SX (2016) Fluorouracil-based neoadjuvant chemoradiotherapy with or without oxaliplatin for treatment of locally advanced rectal cancer: an updated systematic review and meta-analysis. Oncotarget 7:45513–45524

    Article  Google Scholar 

  29. Zhao L, Liu R, Zhang Z, Li T, Li F, Liu H, Li G (2016) Oxaliplatin/fluorouracil-based adjuvant chemotherapy for locally advanced rectal cancer after neoadjuvant chemoradiotherapy and surgery: a systematic review and meta-analysis of randomized controlled trials. Colorectal Dis 18:763–772

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The statistical analyses performed in this article were advised by Catholic Medical Center Clinical Research Coordinating Center.

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea

    Jin Ho Song

  2. Department of Radiation Oncology, College of Medicine, St. Vincent’s Hospital, The Catholic University of Korea, 93-6, Ji-dong, Paldal-gu, Suwon, 442-723, Kyeonggi-do, Seoul, Republic of Korea

    Jong Hoon Lee & Sung Hwan Kim

  3. Department of Surgery, Korea University Ansan Hospital, Seoul, Republic of Korea

    Jun Won Um

Authors
  1. Jin Ho Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jong Hoon Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sung Hwan Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jun Won Um
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

Korean Clinical Practice Guideline for Colon, Rectal Cancer Committee

Corresponding author

Correspondence to Jong Hoon Lee.

Ethics declarations

Ethics approval

Approval of an Institute Review Board was waived because the patient data were collected from administrative data without identifiable personal information.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 325 KB)

Supplementary file2 (DOCX 16 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Song, J.H., Lee, J.H., Kim, S.H. et al. Oxaliplatin-based adjuvant chemotherapy rather than fluorouracil-based chemotherapy in rectal cancer is more efficient to decrease distant metastasis and increase survival after preoperative chemoradiotherapy and surgery: a meta-analysis. Int J Colorectal Dis 37, 649–656 (2022). https://doi.org/10.1007/s00384-022-04096-9

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00384-022-04096-9

Keywords

Search

Navigation