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Treatment of Advanced Anal Cancer

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Anal Cancer

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Abstract

Metastatic anal squamous cell carcinoma, while relatively uncommon, is a difficult disease to treat. Lack of prospective data validating the toxicity and efficacy of various chemotherapeutic regimens has led to heterogeneous treatment of patients with this disease over time. Platinum-doublet chemotherapy, including regimens such as 5-fluorouracil (or capecitabine) and cisplatin, carboplatin and paclitaxel, or 5-fluorouracil, leucovorin, and oxaliplatin, remains a standard in the first-line setting for metastatic anal squamous cell carcinoma. Other systemic therapy options include single-agent regimens (irinotecan, paclitaxel, and others) or triplet chemotherapy (docetaxel, cisplatin, and fluorouracil or mitomycin, adriamycin, and cisplatin). As metastatic anal squamous cell carcinoma often harbors wild-type RAS, anti-epidermal growth factor receptor antibodies such as cetuximab and panitumumab have also been used. Checkpoint inhibitors such as nivolumab and pembrolizumab have demonstrated some efficacy in refractory metastatic anal squamous cell carcinoma. In oligometastatic disease, locoregional approaches after initial systemic therapy have seen some success in highly selected patients. Additional experimental options under investigation for the treatment of metastatic anal squamous cell carcinoma include adoptive T-cell transfer, vaccine therapy, and combinatorial therapy with chemotherapy, biologics, and/or immunotherapy.

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Abbreviations

5-FU:

5-fluorouracil

AE:

Adverse event

ASCC:

Anal squamous cell carcinoma

CC:

Cervical cancer

CI:

Continuous infusion

CP-5-FU:

Cisplatin plus 5-fluorouracil

CPAC:

Carboplatin plus paclitaxel

CP:

Carboplatin

CR:

Complete response

D:

Day

DCF:

Docetaxel, cisplatin, fluorouracil

DCR:

Disease control rate

DFS:

Disease-free survival

EGFR:

Epidermal growth factor receptor

FOLFOX:

5-FU, oxaliplatin and leucovorin

FOLFIRI:

5-FU, irinotecan and leucovorin

G:

Grade

GGT:

Gamma-glutamyltransferase

Gy:

Gray

HIV:

Human immunodeficiency virus

HPV:

Human papillomavirus

IV:

Intravenous

MAP:

Mitomycin C, adriamycin and cisplatin

mASCC:

Metastatic anal squamous cell carcinoma

m2:

Meters squared

mg:

Milligram

NCCN:

National Comprehensive Cancer Network

ORR:

Objective response rate

OS:

Overall survival

PFS:

Progression-free survival

PR:

Partial response

RFA:

Radiofrequency ablation

SD:

Stable disease

TIL:

Tumor-infiltrating lymphocytes

TRAE:

Treatment-related adverse event

WT:

Wild-type

References

  1. Cancer stat facts: anal cancer. Available at https://seer.cancer.gov/statfacts/html/anus.html. Accessed 28 June 2018.

  2. Das P, Bhatia S, Eng C, Ajani JA, Skibber JM, Rodriguez-Bigas MA, et al. Predictors and patterns of recurrence after definitive chemoradiation for anal cancer. Int J Radiat Oncol Biol Phys. 2007;68(3):794–800.

    Article  PubMed  Google Scholar 

  3. Ferris R, Blumenschein G, Fayette J, Guigay J, Colevas D, Licitra L, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375:1856–67.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Hollenbecque A, Meyer T, Moore K, Machiels JP, De Greve J, Lopez-Picazo J, et al. An open-label, multicohort, phase I/II study of nivolumab in patients with virus-associated tumors (CheckMate 358): efficacy and safety in recurrent or metastatic (R/M) cervical, vaginal, and vulvar cancers. J Clin Oncol. 2017;35(15):S5504.

    Article  Google Scholar 

  5. Khater R, Frenay M, Bourry J, Milano G, Namer M. Cisplatin plus 5-fluorouracil in the treatment of metastatic anal squamous cell carcinoma: a report of two cases. Cancer Treat Rep. 1986;70(11):1345–6.

    CAS  PubMed  Google Scholar 

  6. Ajani J, Carrasco H, Jackson D, Wallace S. Combination of cisplatin plus fluoropyrimidine chemotherapy effective against liver metastases from carcinoma of the anal canal. Am J Med. 1989;87(2):221–4.

    Article  CAS  PubMed  Google Scholar 

  7. Jaiyesimi I, Pazdur R. Cisplatin and 5-fluorouracil as salvage therapy for recurrent metastatic squamous cell carcinoma of the anal canal. Am J Clin Oncol. 1993;16(6):536–40.

    Article  CAS  PubMed  Google Scholar 

  8. Faivre C, Rougier P, Ducreux M, Mitry E, Lusinchi A, Lasser P, et al. 5-fluorouracile and cisplatinum combination chemotherapy for metastatic squamous-cell anal cancer. Bull Cancer. 1999;86(10):861–5.

    CAS  PubMed  Google Scholar 

  9. Haydon A, Tay R, Mak G, Shapiro J. Long survival (cure) to cisplatin/Infusional 5-Flurouracil in metastatic squamous cell anal cancer with extensive liver and lung metastases. Case Rep Cli Med. 2015;4(3):73–6.

    Article  Google Scholar 

  10. Eng C, Chang G, You N, Das P, Rodriguez-Bigas M, Xing Y, et al. The role of systemic chemotherapy and multidisciplinary management in improving the overall survival of patients with metastatic squamous cell carcinoma of the anal canal. Oncotarget. 2014;5(22):1133–42.

    Article  Google Scholar 

  11. Kim R, Byer J, Fulp WJ, Mahipal A, Dinwoodie W, Shibata D. Carboplatin and paclitaxel treatment is effective in advanced anal cancer. Oncology. 2014;87(2):125–32.

    Article  CAS  PubMed  Google Scholar 

  12. Rao S, Sclafani F, Eng C, et al. InterAACT: a multicentre open label randomised phase II advanced anal cancer trial of cisplatin (CDDP) plus 5-fluorouracil (5-FU) vs carboplatin (C) plus weekly paclitaxel (P) in patients (pts) with inoperable locally recurrent (ILR) or metastatic treatment naïve disease – an International Rare Cancers Initiative (IRCI) trial. Presented at ESMO 2018, Munich, Germany.

    Google Scholar 

  13. Matsunaga M, Miwa K, Oka Y, Nagasu S, Sakaue T, Fukahori M, et al. Successful treatment of metastatic anal canal adenocarcinoma with mFOLFOX6 + bevacizumab. Case Rep Oncol. 2016;9(1):249–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Jhawer M, Mani S, Lefkopoulou M, Hahn RG, Harris J, Catalano PJ, et al. Phase II study of mitomycin-C, adriamycin, cisplatin (MAP) and bleomycin-CCNU in patients with advanced cancer of the anal canal: an eastern cooperative oncology group study E7282. Investig New Drugs. 2006;24(5):447–54.

    Article  CAS  Google Scholar 

  15. Kim M, Jary M, Mansi L, Benzidane B, Cazorla A, Demarchi M. DCF (docetaxel, cisplatin and 5-fluorouracil) chemotherapy is a promising treatment for recurrent advanced squamous cell anal carcinoma. Ann Oncol. 2012;24(12):3045–50.

    Article  Google Scholar 

  16. Hainsworth JD, Burris HA 3rd, Meluch AA, Baker MN, Morrissey LH, Greco FA. Paclitaxel, carboplatin, and long-term continuous infusion of 5-fluorouracil in the treatment of advanced squamous and other selected carcinomas: results of a phase II trial. Cancer. 2001;92(3):642–9.

    Article  CAS  PubMed  Google Scholar 

  17. Kim S, Francois E, Andre T, Samalin E, Jary M, Hajbi F, et al. Docetaxel, cisplatin, and fluorouracil chemotherapy for metastatic or unresectable locally recurrent anal squamous cell carcinoma (epitopes-HPV02): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2018;19(8):1094–106.

    Article  CAS  PubMed  Google Scholar 

  18. Alcindor T. Activity of paclitaxel in metastatic squamous anal carcinoma. Int J Color Dis. 2008;23(7):717.

    Article  Google Scholar 

  19. Abbas A, Nehme E, Fakih M. Single-agent paclitaxel in advanced anal cancer after failure of cisplatin and 5-fluorouracil chemotherapy. Anticancer Res. 2011;31(12):4637–40.

    CAS  PubMed  Google Scholar 

  20. Evans TR, Mansi JL, Glees JP. Response of metastatic anal carcinoma to single agent carboplatin. Clin Oncol. 1993;5(1):57–8.

    Article  CAS  Google Scholar 

  21. Morris V, Rao X, Pickering C, Foo WC, Rashid A, Eterovic K, et al. Comprehensive genomic profiling of metastatic squamous cell carcinoma of the anal canal. Mol Cancer Res. 2017;15(11):1542–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Gardini A, Capelli L, Ulivi P, Giannini M, Freier E, Tamberi S, et al. KRAS, BRAF and PIK3CA status in squamous cell anal carcinoma (SCAC). PLoS One. 2014;9(3):e92071.

    Article  Google Scholar 

  23. Paliga A, Onerheim R, Gologan A, Spatz A, Vuong T. EGFR expression in invasive anal carcinoma. J Clin Oncol. 2011;29(4):S412.

    Article  Google Scholar 

  24. Phan L, Hoff PM. Evidence of clinical activity for Cetuximab combined with irinotecan in a patient with refractory Anal Canal squamous-cell carcinoma: report of a case. Dis Colon Rectum. 2007;50(3):395–8.

    Article  PubMed  Google Scholar 

  25. Lukan N, Ströbel P, Willer A, Kripp M, Dinter D, Mai S, et al. Cetuximab-based treatment of metastatic anal cancer: correlation of response with KRAS mutational status. Oncology. 2009;77(5):293–9.

    Article  CAS  PubMed  Google Scholar 

  26. Klimant E, Markman M. Management of two cases of recurrent anal carcinoma. Case Rep Oncol. 2013;6(3):456–61.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Rogers JE, Ohinata A, Silva NN, Mehdizadeh A, Eng C. Epidermal growth factor receptor inhibition in metastatic anal cancer. Anti-Cancer Drugs. 2016;27(8):804–8.

    Article  CAS  PubMed  Google Scholar 

  28. Khawandanah M, Baxley A, Pant S. Recurrent metastatic anal cancer treated with modified paclitaxel, ifosfamide, and cisplatin and third-line mitomycin/cetuximab. J Oncol Pharm Prac. 2015;21(3):232–7.

    Article  CAS  Google Scholar 

  29. Barmettler H, Komminoth P, Schmid M, Duerr D. Efficacy of Cetuximab in combination with FOLFIRI in a patient with KRAS wild-type metastatic anal cancer. Case Rep Oncol. 2012;5(2):428–33.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Meulendijks D, Tomasoa NB, Dewit L, Smits PM, Bakker R, Van Velthuysen ML, et al. HPV-negative squamous cell carcinoma of the anal canal is unresponsive to standard treatment and frequently carries disruptive mutations in TP53. Br J Cancer. 2015;112:1358–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Shridhar R, Shibata D, Chan E, Thomas C. Anal cancer: current standards in care and recent changes in practice. CA Cancer J Clin. 2015;65(2):139–62.

    Article  PubMed  Google Scholar 

  32. Morris VK, Salem ME, Nimeiri H, Iqbal S, Singh P, Ciombor K, et al. Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2017;18(4):446–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ott, et al. Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal. Ann Oncol. 2017;28(5):1036–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Rosenberg S, Restifo N. Adoptive cell transfer as personalized immunotherapy for human cancer. Science. 2015;348(6230):62–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Stevanovic S, Draper L, Langhan M, Campbell T, Kwong ML, Wunderlich R, et al. Complete regression of metastatic cervical Cancer after treatment with human papillomavirus–targeted tumor-infiltrating T cells. J Clin Oncol. 2015;33(14):1543–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Hinrichs C, Doran S, Stevanovic S, Adhikary S, Mojadidi M, Kwong ML, et al. A phase I/II clinical trial of E6 T-cell receptor gene therapy for human papillomavirus (HPV)-associated epithelial cancers. J Clin Oncol. 2017;35(15):S3009.

    Article  Google Scholar 

  37. Tan S, De Vries EG, Van Der Zee AG, De Jong S. Anticancer drugs aimed at E6 and E7 activity in HPV-positive cervical cancer. Cur Cancer Drug Tar. 2012;12(2):170–84.

    Article  CAS  Google Scholar 

  38. Maciag PC, Radulovic S, Rothman J. The first clinical use of a live-attenuated listeria monocytogenes vaccine: a phase I safety study of Lm-LLO-E7 in patients with advanced carcinoma of the cervix. Vaccine. 2009;27(30):3975–83.

    Article  CAS  PubMed  Google Scholar 

  39. Fakih M, O’Neil B, Chiorean EG, Hochster H, Chan E, Mauro D, et al. Phase II study of ADXS11-001 in patients with persistent/recurrent, locoregional or metastatic squamous cell carcinoma of the anorectal canal. J Clin Oncol. 2016;34(4.):suppl):TPS786.

    Article  Google Scholar 

  40. Zhao J, Cao Y, Lei Z, Yang Z, Zhang B, Huang B. Selective depletion of CD4+CD25+Foxp3+ regulatory T cells by low-dose cyclophosphamide is explained by reduced intracellular ATP levels. Cancer Res. 2010;70(12):4850–8.

    Article  CAS  PubMed  Google Scholar 

  41. Ma D, Clark E. The role of CD40 and CD40L in dendritic cells. Semin Immunol. 2009;21(5):265–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Johnson P, Challis R, Chowdury F, Gao Y, Harvey M, Geldart T, et al. Clinical and biological effects of an agonist anti-CD40 antibody. A Cancer Research UK phase I study. Clin Cancer Res. 2015;21(6):1321–8.

    Article  CAS  PubMed  Google Scholar 

  43. Rogers J, Crane C, Das P, Delclos M, Gould M, Ohinata A, et al. Definitive chemoradiation in oligometastatic squamous cell carcinoma of the anal canal. Gastrointest Cancer Res. 2014;7(2):65–8.

    PubMed  PubMed Central  Google Scholar 

  44. Hodges JC, Das P, Eng C, Reish AG, Beddar AS, Delclos ME, et al. Intensity-modulated radiation therapy for the treatment of squamous cell anal cancer with para-aortic nodal involvement. Int J Radiat Oncol Biol Phys. 2009;75(3):791–4.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Pawlik TM, Gleisner AL, Bauer TW, Adams RB, Reddy SK, Clary BM, et al. Liver-directed surgery for metastatic squamous cell carcinoma to the liver: results of a multi-center analysis. Ann Surg Oncol. 2007;14(10):2807–16.

    Article  PubMed  Google Scholar 

  46. Joe MB, Lum JJ, Watson PH, Tonseth RP, McGhie JP, Truong PT. Radiation generates an abscopal response and complete resolution of metastatic squamous cell carcinoma of the anal canal: a case report. J Gastrointest Oncol. 2017;8(6):E84–9.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

    Satya Das & Kristen Keon Ciombor

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  1. Satya Das
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  2. Kristen Keon Ciombor
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Correspondence to Kristen Keon Ciombor .

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Editors and Affiliations

  1. Department of Radiation Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA

    Jeffrey Meyer

  2. Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, TN, USA

    Lisa Kachnic

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Das, S., Ciombor, K.K. (2019). Treatment of Advanced Anal Cancer. In: Meyer, J., Kachnic, L. (eds) Anal Cancer. Springer, Cham. https://doi.org/10.1007/978-3-030-20253-8_7

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  • DOI: https://doi.org/10.1007/978-3-030-20253-8_7

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