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Current and Emerging Treatment Strategies for Anal Cancer

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Abstract

Concurrent radiotherapy and chemotherapy (5-fluorouracil and mitomycin-C) is established as a sphincter-preserving treatment for squamous cell carcinoma of the anal canal. However, there is room for improvement in rates of tumor control as well as a need to reduce treatment-induced toxicity. Efforts are underway to test the value of newer radiosensitizing chemotherapeutic and molecular targeted agents, as well as to establish the value of advances in radiation therapy planning and delivery. This review discusses the evolution of therapy for anal cancer, from early clinical trials establishing the current standard to more recent studies evaluating cisplatin, capecitabine, oxaliplatin, and cetuximab. Early clinical results from studies incorporating intensity-modulated radiation therapy are also discussed.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Forastiere AA, Goepfert H, Maor M, et al.: Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. New Engl J Med 2003, 349:2091–2098.

    Article  CAS  PubMed  Google Scholar 

  2. Nigro ND, Vaitkevicius VK, Considine B Jr: Combined therapy for cancer of the anal canal: a follow-up report. Dis Colon Rectum 1977, 20:677–678.

    Article  PubMed  Google Scholar 

  3. Boman BM, Moertel CG, O’Connell MJ, et al.: Carcinoma of the anal canal. A clinical and pathologic study of 188 cases. Cancer 1984, 54:114–125.

    Article  CAS  PubMed  Google Scholar 

  4. Nigro ND, Vaitkevicius VK, Considine B Jr: Combined therapy for cancer of the anal canal: a preliminary report. Dis Colon Rectum 1974, 17:354–356.

    Article  CAS  PubMed  Google Scholar 

  5. Epidermoid anal cancer: results from the UKCCCR randomized trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. UKCCCR Anal Cancer Trial Working Party. UK Co-ordinating Committee on Cancer Research. Lancet 1996, 348:1049–1054.

    Google Scholar 

  6. 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, 15:2040–2049.

    CAS  PubMed  Google Scholar 

  7. Flam M, John M, Pajak T, 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, 14:2527–2539.

    CAS  PubMed  Google Scholar 

  8. Ajani J, Winter K, Gunderson L, et al.: Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal. A randomized controlled trial. JAMA 2008, 299:1914–1921.

    Article  CAS  PubMed  Google Scholar 

  9. James R, Wan S, Glynne-Jones R, et al.: A randomized trial of chemoradiation using mitomycin or cisplatin, with or without maintenance cisplatin/5FU in squamous cell carcinoma of the anus (ACT II) [suppl; abstr LBA4009]. J Clin Oncol 2009, 27:18s.

    Article  Google Scholar 

  10. Conroy T, Ducreux M, Lemanski C, et al.: Treatment intensification by induction chemotherapy (ICT) and radiation dose escalation in locally advanced squamous cell anal carcinoma (LAAC): definitive analysis of the intergroup ACCORD 03 trial [abstract 4033]. J Clin Oncol 2009, 27(Suppl 1).

  11. Matzinger O, Roelofsen F, Mineur L, et al.: Mitomycin C with continuous fluorouracil or with cisplatin in combination with radiotherapy for locally advanced anal cancer (European Organisation for Research and Treatment of Cancer phase II study 22011-40014). Eur J Cancer 2009, 45:2782–2791.

    Article  CAS  PubMed  Google Scholar 

  12. Miwa M, Ura M, Nishida M, et al.: Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumors by enzymes concentrated in human liver and cancer tissue. Eur J Cancer 1998, 34:1274–1281.

    Article  CAS  PubMed  Google Scholar 

  13. Glynne-Jones R, Meadows H, Wan S, et al.: EXTRA—a multicenter phase II study of chemoradiation using a 5 day per week oral regimen of capecitabine and intravenous mitomycin C in anal cancer. Int J Radiat Oncol Biol Phys 2008, 72:119–126.

    CAS  PubMed  Google Scholar 

  14. Folkvord S, Flatmark K, Seierstad T, et al.: Inhibitory effects of oxaliplatin in experimental radiation treatment of colorectal carcinoma: does oxaliplatin improve 5-fluorouracil-dependent radiosensitivity? Radiother Oncol 2008, 86:428–434.

    Article  CAS  PubMed  Google Scholar 

  15. Sawada N, Kondoh K, Mori K: Enhancement of capecitabine efficacy by oxaliplatin in human colorectal and gastric cancer xenografts. Oncol Rep 2007, 18:775–778.

    CAS  PubMed  Google Scholar 

  16. Eng C, Chang GJ, Das P, et al.: Phase II study of capecitabine and oxaliplatin with concurrent radiation therapy (XELOX-XRT) for squamous cell carcinoma of the anal canal [abstr 4116]. J Clin Oncol 2009, 27(Suppl):15s.

    Google Scholar 

  17. Chen DJ, Nirodi CS: The epidermal growth factor: a role in repair of radiation-induced DNA damage. Clin Cancer Res 2007, 12:6555–6560.

    Article  Google Scholar 

  18. Milas L, Mason K, Hunter N, et al.: In vivo enhancement of tumor radioresponse by C225 antiepidermal growth factor receptor antibody. Clin Cancer Res 2000, 6:701–707.

    CAS  PubMed  Google Scholar 

  19. Bonner JA, Harari PM, Giralt J, et al.: Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol 2010, 11:21–28.

    Article  CAS  PubMed  Google Scholar 

  20. Karapetis CS, Khambata-Ford S, Jonker DJ, et al.: K-ras mutations and benefit from cetuximab in advanced colorectal cancer. New Engl J Med 2008, 359:1757–1765.

    Article  CAS  PubMed  Google Scholar 

  21. Zampino MG, Magni E, Sonzogni A, et al.: K-ras status in squamous cell anal carcinoma (SCC): it’s time for target-oriented treatment? Cancer Chemother Pharmacol 2009, 65:197–199. There is a lack of data regarding molecular predictors of response to targeted drug therapy for anal cancer. This report is one of the first to evaluate K-ras status for this disease.

    Article  CAS  PubMed  Google Scholar 

  22. Olivatto LO, Meton F, Bezerra M, et al.: Phase I study of cetuximab (CET) in combination with 5-fluorouracil (5-FU), cisplatin (CP), and radiotherapy (RT) in patients with locally advanced squamous cell anal carcinoma (LAAC) [abstr 4609]. J Clin Oncol 2008, 26(Suppl).

  23. Abrams RA, Winter KA, Regine WF, et al.: Correlation of RTOG 9704 (adjuvant therapy (rx) of pancreatic adenocarcinoma (pan ca)) radiation therapy quality assurance scores (RTQASc) with survival (S) [abstr 4523]. J Clin Oncol 2007, 25(Suppl).

  24. Myerson RJ, Garofalo MC, El Naqa I, et al.: Elective clinical target volumes for conformal therapy in anorectal cancer: a Radiation Therapy Oncology Group consensus panel contouring atlas. Int J Radiat Oncol Biol Phys 2009, 74:824–830. This consensus report from the RTOG helps standardize anal cancer clinical treatment volumes.

    PubMed  Google Scholar 

  25. Salama JK, Mell L, Schomas DA, et al.: Concurrent chemotherapy and intensity-modulated radiation therapy for anal canal cancer patients: a multicenter experience. J Clin Oncol 2007, 25:4581–4586.

    Article  CAS  PubMed  Google Scholar 

  26. Pepek JM, Willett CG, Clough RW, et al.: Intensity modulated radiation therapy (IMRT) for anal cancer: The Duke University experience. Int J Radiat Oncol Biol Phys 2009, 75(Suppl):S267.

    Google Scholar 

  27. Kachnic L, Winter K, Myerson R, et al.: RTOG 0529: A phase II evaluation of dose-painted IMRT in combination with 5-fluorouracil and mitomycin-C for reduction of acute morbidity in carcinoma of the anal canal. Int J Radiat Oncol Biol Phys 2009, 75(Suppl):S5. This is the first report of the RTOG clinical study evaluating the value of IMRT in reducing treatment toxicity.

    Google Scholar 

  28. Hoffman R, Welton ML, Klencke B, et al.: The significance of pretreatment CD4 count on the outcome and treatment tolerance of HIV-positive patients with anal cancer. Int J Radiat Oncol Biol Phys 1999, 44:127–131.

    Article  CAS  PubMed  Google Scholar 

  29. Seo Y, Kinsella MT, Reynolds HL, et al.: Outcomes of chemoradiotherapy with 5-flurorouracil and mitomycin C for anal cancer in immunocompetent versus immunodeficient patients. Int J Radiat Oncol Biol Phys 2009, 75:143–149.

    CAS  PubMed  Google Scholar 

  30. Chiao EY, Giorfano TP, Richardson P, et al.: Human immunodeficiency virus-associated squamous cell cancer of the anus: epidemiology and outcomes in the highly active antiretroviral therapy era. J Clin Oncol 2008, 26:474–479.

    Article  PubMed  Google Scholar 

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Correspondence to Jeffrey Meyer.

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Meyer, J., Willett, C. & Czito, B. Current and Emerging Treatment Strategies for Anal Cancer. Curr Oncol Rep 12, 168–174 (2010). https://doi.org/10.1007/s11912-010-0100-9

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