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Category: Volume 07 Issue 08 August 2019
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Title: Chemoradiotherapy of Locally-Advanced Anal Canal Squamous Cell Carcinoma: A Brief Review of Outcomes of Randomized Clinical Trials

Authors: Erkan Topkan, MD, Huseyin Mertsoylu, MD, Ahmet Kucuk, MD

 DOI: https://dx.doi.org/10.18535/jmscr/v7i8.164

Abstract

     

First-line treatment of locally advanced anal canal squamous cell carcinomas (AC-SCC) has evolved from the abdominoperineal resection resulting in permanent colostomies to definitive concurrent chemoradiotherapy, with surgery reserved for salvage. Publication of small but practice-changing chemoradiotherapy studies in the second half of the 1970s prompted the conduction of large phase III randomized controlled trials consequences of which increased our ability to deliver systemic chemotherapy more effectively and reduce treatment-related toxicity rates by utilizing more sophisticated radiotherapy techniques. This article aims to review the design and outcomes of currently accessible phase III randomized controlled chemoradiotherapy trials of AC-SCC.   

References

  1. Nelson VM, Benson AB 3rd. Epidemiology of Anal Canal Cancer.. Surg Oncol Clin N Am. 2017;26(1):9-15.
  2. Glynne-Jones R, Rao S. Treatment of the Primary Tumor in Anal Canal Cancers. Surg Oncol Clin N Am. 2017;26(1):73-90.
  3. Sato H, Koh P, Bartolo DC. Management of anal canal carcinoma. Dis Colon Rectum 2005;48:1301-15.
  4. Nigro ND, Vaitkevicius VK, Considine B. Combined therapy for cancer of the anal canal: a preliminary report. Dis Colon Rectum 1974;17:354-6.
  5. Leichman L, Nigro ND, Vaitkevicius VK. Cancer of the anal canal. Model for preoperative adjuvant combined modality therapy. Am J Med. 1985;78(2):211-5.
  6. Northover J, Glynne-Jones R, Cunningham D, et al. Epidermoid anal cancer: results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. Lancet. 1996;348(9034):1049-54.
  7. Northover J, Glynne-Jones R, Sebag-Montefiore D, et al. Chemoradiation for the treatment of epidermoid anal cancer: 13-year follow-up of the first randomised UKCCCR Anal Cancer Trial (ACT I). Br J Cancer. 2010 30;102(7):1123-8.
  8. Bartelink H, Roelofsen F, Eschwege F, et al. Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: results of a phase III randomized trial of the European Organization for Research and Treatment of Cancer Radiotherapy and Gastrointestinal Cooperative Groups. J Clin Oncol. 1997;15(5):2040-9.
  9. Flam M, John M, Pajak TF, et al. Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. J Clin Oncol. 1996;14(9):2527-39.
  10. Ajani JA, Winter KA, Gunderson LL, et al. Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial. JAMA.2008;299(16):1914-21.
  11. Gunderson LL, Winter KA, Ajani JA, et al. Long-term update of US GI intergroup RTOG 98-11 phase III trial for anal carcinoma: survival, relapse, and colostomy failure with concurrent chemoradiation involving fluorouracil/ mitomycin versus fluorouracil/cisplatin. J Clin Oncol. 2012;30(35):4344-51.
  12. James RD, Glynne-Jones R, Meadows HM, et al. Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2 × 2 factorial trial. Lancet Oncol.2013;14(6):516-24.
  13. Glynne-Jones R, Sebag-Montefiore D, Meadows HM, et al. Best time to assess complete clinical response after chemoradiotherapy in squamous cell carcinoma of the anus (ACT II): a post-hoc analysis of randomised controlled phase 3 trial. Lancet Oncol. 2017;18(3):347-56.
  14. Peiffert D, Tournier-Rangeard L, Gérard JP, et al. Induction chemotherapy and dose intensification of the radiation boost in locally advanced anal canal carcinoma: final analysis of the randomized UNICANCER ACCORD 03 trial. J Clin Oncol. 2012;30(16):1941-8.
  15. Wegner RE, Abel S, Hasan S, et al. trends in radiation dose and technique for anal canal squamous cell carcinoma. Am J Clin Oncol. 2019;42(6):519-26.
  16. Olsen JR, Moughan J, Myerson R, et al. Predictors of radiation therapy-related gastrointestinal toxicity from anal cancer dose-painted intensity modulated radiation therapy: secondary analysis of NRG Oncology RTOG 0529. Int J Radiat Oncol Biol Phys. 2017;98:400-8.
  17. Olivatto LO, Vieira FM, Pereira BV, et al. Phase 1 study of cetuximab in combination with 5-fluorouracil, cisplatin, and radiotherapy in patients with locally advanced anal canal carcinoma. Cancer. 2013;119(16):2973-80.
  18. Deutsch E, Lemanski C, Pignon JP, et al. Unexpected toxicity of cetuximab combined with conventional chemoradiotherapy in patients with locally advanced anal cancer: results of the UNICANCER ACCORD 16 phase II trial. Ann Oncol. 2013;24(11):2834-8.
  19. Garg MK, Zhao F, Sparano JA, et al.Cetuximab Plus Chemoradiotherapy in Immunocompetent Patients With Anal Carcinoma: A Phase II Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group Trial (E3205). J Clin Oncol. 2017;35(7):718-26.
  20. Casadei Gardini A, Passardi A, Fornaro L, et al. Treatment of squamous cell carcinoma of the anal canal: A new strategies with anti-EGFR therapy and immunotherapy. Crit Rev Oncol Hematol. 2018;123:52-56.

Corresponding Author

Erkan Topkan, MD

Baskent University Medical Faculty, Department of Radiation Oncology, 01120, Adana, TURKEY