Skip to main content

Advertisement

SpringerLink
Log in

The Use of Single-Agent Versus Multiple-Agent Concurrent Chemoradiotherapy in the Treatment of Locally Advanced Rectal Cancer

  • Original Research
  • Published:
Journal of Gastrointestinal Cancer Aims and scope Submit manuscript

Abstract

Purpose

The use of concurrent chemoradiotherapy is frequently recommended in the treatment of locally advanced rectal cancer; however, the ideal chemotherapy regimen remains unknown, and there is variability in chemotherapy agents used among different institutions. We sought to examine differences in overall survival between patients receiving single versus multiple-agent concurrent chemoradiotherapy.

Methods

The National Cancer Database was used to identify 31,025 patients with rectal cancer who received concurrent chemoradiotherapy between 01/2006 and 12/2016. We compared patients who received single-agent chemotherapy with those who received multiple-agent concurrent chemoradiotherapy. The primary outcome of interest was overall survival. The groups were compared using univariate analysis and Cox proportional hazard models to adjust for potential confounding factors.

Results

18,544 patients received single-agent and 12,481 patients received multiple-agent chemotherapy. The former were older with more comorbidities as evidenced by their higher Charlson-Deyo Scores. Those receiving multiple-agent chemotherapy were more likely to have clinical stage III disease (52.9% vs 43.3%, p < 0.001) and less likely to have well-differentiated cancer (6.9% vs 7.7%, p < 0.001). The rates of negative resection margin were identical (p = 0.225) between the two groups. On multivariable analysis after adjusting for comorbidities, radiation dose, and resection margins, single-agent chemotherapy was associated with worse overall survival (HR 1.09, 95% CI 1.057–1.124, p < 0.001).

Conclusion

Multiple-agent chemoradiotherapy is associated with improved overall survival in locally advanced rectal cancer; however, chemotherapy regimen does not affect resection margins. The modest overall survival benefit with multiple-agent chemotherapy must be balanced with the potential associated toxicity.

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

Similar content being viewed by others

Availability of Data and Material

From the corresponding author upon reasonable request.

References

  1. Sebag-Montefiore D, Stephens RJ, Steele R, et al. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicenter, randomized trial. Lancet. 2009;373:811–20.

    Article  Google Scholar 

  2. Van Gijn W, Marijnen CA, Nagtegaal ID, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicenter, randomized controlled TME trial. Lancet Oncol. 2011;12:575–82.

    Article  Google Scholar 

  3. National Comprehensive Cancer Network. Rectal Cancer (Version 6.2020). Retrieved from https://www.nccn.org/professionals/physician_gls/pdf/rectal.pdf.

  4. Bosset JF, Collette L, Galais G, et al. Chemotherapy with preoperative radiotherapy in rectal cancer. N End J Med. 2006;355:1114–23.

    Article  CAS  Google Scholar 

  5. Bonnetain F, Bosset JF, Gerard JP, et al. What is the clinical benefit of preoperative chemoradiotherapy with 5FU/leucovorin for T3–T4 rectal cancer in a pooled analysis of EORT 22921 and FFCD 9203 trials: surrogacy in question? Eur J Cancer. 2012;48:1781–90.

    Article  CAS  Google Scholar 

  6. Rodel C, Liersch T, Becker H, et al. Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomized phase 3 trial. Lancet Oncol. 2012;13:679–87.

    Article  Google Scholar 

  7. Rodel C, Graeven U, Fietkau R, et al. 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 multicenter, open-label, randomized, phase 3 trial. Lancet Oncol. 2015;16:979–89.

    Article  Google Scholar 

  8. Aschele C, Cionini L, Lonardi S, et al. 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. 2011;29:2773–80.

    Article  CAS  Google Scholar 

  9. Rodel C, Hofheinz R, Fokas E. Rectal cancer: neoadjuvant chemoradiotherapy. Best Pract Res Clin Gatroenterol. 2016;30:629–39.

    Article  Google Scholar 

  10. Gerard JP, Azria D, Gourgou-Bourgade S, et al. Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-Prodige 2. J Clin Oncol. 2010;28:1638–44.

    Article  CAS  Google Scholar 

  11. Gerard JP, Azria D, Gourgou-Bourgade S, et al. Clinical outcome of the ACCORD 12/0405 PRODIGE 2 randomized trial in rectal cancer. J Clin Oncol. 2012;30:4558–65.

    Article  CAS  Google Scholar 

  12. Allegra CJ, Yothers G, O’Connell MJ, et al. Neoadjuvant 5-FU or capecitabine plus radiation with or without oxaliplatin in rectal cancer patients: a phase III randomized clinical trial. J Natl Cancer Inst 2015;107:djv248.

  13. Hong YS, Kim SY, Lee JS, et al. Oxaliplatin-based adjuvant chemotherapy for rectal cancer after preoperative chemoradiotherapy (ADORE): long-term results of a randomized controlled trial. J Clin Oncol. 2019;37:3111–23.

    Article  CAS  Google Scholar 

  14. Hong YS, Nam BH, Kim KP, et al. Oxaliplatin, fluorouracil, and leucovorin versus fluorouracil and leucovorin as adjuvant chemotherapy for locally advanced rectal cancer after preoperative chemoradiotherapy (ADORE): an open-label, multicenter, phase 2, randomized controlled trial. Lancet Oncol. 2014;15:1245–53.

    Article  CAS  Google Scholar 

  15. Hofheinz RD, Arnold D, Fokas E, et al. Impact of age on the efficacy of oxaliplatin in the preoperative chemoradiotherapy and adjuvant chemotherapy of rectal cancer: a post hoc analysis of the CAO/ARO/AIO-04 phase III trial. Ann Oncol. 2018;29:1793–9.

    Article  CAS  Google Scholar 

Download references

Funding

No funding or external support was received for this study.

Author information

Authors and Affiliations

  1. Department of Surgery, Massachusetts General Hospital, 55 Fruit St. GRB-425, MA, 02114, Boston, USA

    Thomas Peponis, Caitlin Stafford, James Cusack, Christy Cauley, David Berger, Liliana Bordeianou, Hiroko Kunitake & Rocco Ricciardi

  2. Department of Surgery, Newton Wellesley Hospital, Newton, MA, USA

    Robert Goldstone & Todd Francone

  3. Cancer Center, Massachusetts General Hospital, Boston, MA, USA

    Aparna Parikh

Authors
  1. Thomas Peponis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Caitlin Stafford
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. James Cusack
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christy Cauley
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Robert Goldstone
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. David Berger
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Aparna Parikh
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Liliana Bordeianou
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hiroko Kunitake
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Todd Francone
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Rocco Ricciardi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

TP and RR conceived and designed the research project. CS and RR collected the data used. TP and RR did the statistical analysis of the data. TP, CS, JC, CC, RG, DB, AP, LB, HK, TF, and RR performed a critical interpretation of the data. TP and RR wrote the initial version of the manuscript. CS, JC, CC, RG, DB, AP, LB, HK, and TF reviewed, edited the manuscript, and contributed to its final form. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Thomas Peponis.

Ethics declarations

Ethics Approval

Our study protocols were considered exempt by our Institutional Review Board.

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.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Peponis, T., Stafford, C., Cusack, J. et al. The Use of Single-Agent Versus Multiple-Agent Concurrent Chemoradiotherapy in the Treatment of Locally Advanced Rectal Cancer. J Gastrointest Canc 53, 557–563 (2022). https://doi.org/10.1007/s12029-021-00657-3

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12029-021-00657-3

Keywords

Search

Navigation