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Phase II Study of Capecitabine in Substitution of 5-FU in the Chemoradiotherapy Regimen for Patients with Localized Squamous Cell Carcinoma of the Anal Canal

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Abstract

Summary

This was a phase II study of capecitabine in substitution of 5-fluorouracil (5-FU) in the chemoradiotherapy regimen for patients with localized squamous cell carcinoma of the anal canal.

Background

Combined chemoradiation with infusional 5-FU and mitomycin is the standard treatment for localized squamous cell carcinoma (SCC) of the anal canal. Capecitabine is an oral fluoropirimidine that has been shown to be equally effective to 5-FU in many solid tumors. However, the efficacy of the substitution of 5-FU for capecitabine in anal SCC needs confirmation.

Methods

Patients with SCC of anal cancer T2-4N0M0 or T (any) N1-3M0, with good performance status and normal blood and renal function, were treated with capecitabine 825 mg/m2 bid during radiotherapy associated with a single dose of mitomycin 15 mg/m2 on day 1. The primary objective was local control rate at 6 months determined by clinical examination and radiological assessment. Sample size was calculated using the Fleming single-stage design.

Results

From November 2010 to February 2014, N = 51 patients were initially included; however, 43 patients were assessed. Seventeen patients (39.5 %) were stage II, 11 patients (25.6 %) stage IIIA, and 15 patients (34.9 %) stage IIIB. Four patients (9.3 %) were HIV positive. With a median follow-up of 23.1 months (range 4 to 44.4 months), 3 patients (7 %) presented partial response, 37 (86 %) had complete response, and 3 patients developed progression of the disease (7 %) at 6 months. The colostomy rate was 18.6 %. It was observed a locoregional control of 86 % in 6 months (CI 95 % 0.72–0.94). The main grade 3–4 toxicities were grade 3 radiodermitis in 10 patients (23.2 %), grade 3 lymphopenia in 5 patients (11.6 %), and grade 3 neutropenia in 2 patients (6.9 %). One HIV-positive patient had septic shock, pneumonia, herpetic encephalitis, atrial fibrillation, and macrophage activation syndrome.

Conclusions

Capecitabine can safely substitute infusional 5-FU in the standard chemoradiation regimen for SCC of the anal cancer, with a locoregional control of 86 % in 6 months (CI 95 % 0.72–0.94).

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References

  1. National Cancer Institute at the National Institutes of Health [Internet] [Place unknown][date unknown]. Available from: http://www.cancer.gov/cancertopics/pdq/treatment/anal/HealthProfessional/page2

  2. Patel H, Polanco-Echeverry G, Segditas S, et al. Activation of AKT and nuclear accumulation of wild type TP53 and MDM2 in anal squamous carcinoma. Int J Cancer. 2007;121:2668–73.

    Article  CAS  PubMed  Google Scholar 

  3. Glynne-Jones R, Nilsson PJ, Aschele C, Goh V, et al. Anal cancer: ESMO-ESSO-ESTRO clinical practice guidelines for diagnosis, treatment and follow-up. Ann of Oncol. 2014;00:1–11.

    Google Scholar 

  4. UKCCR Anal Cancer Working party. Epidermoid anal cancer: results from the UKCCR randomized trial of radiotherapy alone versus radiotherapy, 5- fluorouracil and mitomycin. Lancet. 1996;348:1049–54.

    Article  Google Scholar 

  5. 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;15:2040–9.

    CAS  PubMed  Google Scholar 

  6. Bosset JF, Roelofsen F, Morgan DAL, et al. Shortened irradiation schedule, continous infusion of 5-fluorouracil and fractionation of mitomycin in locally advanced anal carcinomas. Results of a phase II study of the European Organization for Research and Treatment of Cancer Radiotherapy and Gastrointestinal Cooperative Groups. Eur J Cancer. 2003;39:45–51.

    Article  CAS  PubMed  Google Scholar 

  7. Park JH, Yoon SH, Yu CS, Kim JH, Kim TW, Kim JC. Ramdomized phase 3 trial comparing preoperative and postoperative chemoradiotherapy with capecitabine for locally advanced rectal cancer. Cancer. 2011;117(16):3703.

    Article  CAS  PubMed  Google Scholar 

  8. Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, et al. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012;13:579–88.

    Article  CAS  PubMed  Google Scholar 

  9. Allegra CJ, Yothers G, O'Connell MJ, Beart RW, Wozniak TF, Pitot HC, Shields AF, Landry JC, Ryan DP, Arora A, Evans LS, Bahary N, Soori G, Eakle JF, Robertson JM, Moore DF Jr, Mullane MR, Marchello BT, Ward PJ, Sharif S, Roh MS, Wolmark N. 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. Nov;107(11). doi:10.1093/jnci/djv248.

  10. Glynne- Jones R, Meadows H, Wan s, et al. National cancer research institute anal subgroup and colorectal clinical oncology group. EXTRA—a multicenter phase II study of chemoradiation using a 5 day per week oral regimen of capecitabine and intravenous mitomycin in anal cancer. Int J Radiation Oncol Biol Phys. 2008;72(1):119–26.

    Article  CAS  Google Scholar 

  11. Deenen MJ, Dewit L, Boot H, Beijnen JH, Schellens JHM, Cats A. Simultaneous integrated boost-intensity modulated radiation therapy with concomitant capecitabine and mitomycin C for locally advanced anal carcinoma: a phase 1 study. Int J Radiation Oncol Biol Phys. 2013;85(5):201–7.

    Article  Google Scholar 

  12. Thind G, Johal B, Follwell M, Kennecke HF. Chemoradiation with capecitabine and mitomycin-C for stage I-III anal squamous cell carcinoma. Radiat Oncol. 2014;9:124.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Meulendjiks D, Dewit L, Tomasoa NB, van Tinteren H, Beijnen JH, Schellens JH, et al. Chemoradiation with capecitabine for locally advanced anal carcinoma: an alternative treatment option. Br J cancer. 2014;111(99):1726–33.

    Article  Google Scholar 

  14. Chin JY, Hong TS, Ryan DP. Mitomycin in anal cancer: still the standard of care. J Clin Oncol. 2012;Vol 30(No 35 (December 10)):4297–301.

    Article  Google Scholar 

  15. Nigro N, Vaitkevicius VK, Considine B. Combined therapy for cancer of the anal canal: a preliminary report. Dis Colon Rectum. 1974;17:354–69.

    Article  CAS  PubMed  Google Scholar 

  16. 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;199:1914–21.

    Article  Google Scholar 

  17. 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;14:2527–39.

    CAS  PubMed  Google Scholar 

  18. Constantinou EC, Daly W, Fung CY, Willett CG, Kaufman DS, Delane TF. Time -dose consideration in the treatment of anal cancer. Int J Radiat Oncol Biol Phys. 1997;39(3):657.

    Article  Google Scholar 

  19. John M, Pajok T, Flam M, Hoffman J, Markoe A, Wolkov H, et al. Dose escalation in chemoradiation for anal cancer:preliminary results of RTOG 92–08. Cancer J Sci Am. 1996;2(4):205.

    CAS  PubMed  Google Scholar 

  20. Martenson JA, Lipsitz SR, Wagner Jr H, Kaplan E, Otteman LA, Schuchter LM, et al. Initial results of a phase II trial of high dose radiation therapy, 5-fluorouracil, and cisplatin for patients with anal cancer (E4292): an Eastern Cooperative Oncology Group study. Int J Radiat Oncol Biol Phys. 1996;35(4):745.

    Article  CAS  PubMed  Google Scholar 

  21. Glynne-Jones R, Adams RA, Jidal M, Meadows H. Endpoints in anal cancer: hopes for a common language. J Clin Oncol 2014;32(12):1281–2.doi:10.1200/JCO.2014.55.1515.

  22. Glynne-Jones R, James R, Meadows H, Begum R, et al. Optimum time to assess complete clinical response (CR) following chemoradiation (CRT) using mitomycin (MMC) or cisplatin (CisP), with or without maintenance CisP/5FU in squamous cell carcinoma of the anus: Results of ACT II. J Clin Oncol 30, 2012;30(15) suppl (May 20 Supplement 4004).

  23. Common terminology criteria for adverse events Version 4.0.[Internet][Place unknown][cited 2010 June 2014]. Available from: http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06 -14

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Authors and Affiliations

  1. Universidade de Sao Paulo, Sao Paulo, Sao Paulo, Brazil

    Suilane Coelho Ribeiro Oliveira, Camila Motta Venchiarutti Moniz, Rachel Riechelmann, Alexandra Kichfy Alex, Maria Ignez Braghirolli, Giovanni Bariani, Caio Nahas & Paulo Marcelo Gehm Hoff

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  1. Suilane Coelho Ribeiro Oliveira
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  2. Camila Motta Venchiarutti Moniz
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  3. Rachel Riechelmann
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Correspondence to Suilane Coelho Ribeiro Oliveira.

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The authors declare that they have no competing interests.

Ethics Approval

The study was conducted in accordance with local ethical and regulatory requirements. It followed the recommendations to conduct clinical trials of the International Conference on Harmonization Good Clinical Practices. Informed consent was applied to all patients before inclusion in the study.

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Oliveira, S.C.R., Moniz, C.M.V., Riechelmann, R. et al. Phase II Study of Capecitabine in Substitution of 5-FU in the Chemoradiotherapy Regimen for Patients with Localized Squamous Cell Carcinoma of the Anal Canal. J Gastrointest Canc 47, 75–81 (2016). https://doi.org/10.1007/s12029-015-9790-4

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  • DOI: https://doi.org/10.1007/s12029-015-9790-4

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