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Immediate and long-term results of radiation therapy in combination with capecitabine and oxaliplatin in the treatment of patients with asquamous cell carcinoma of the anus

https://doi.org/10.21294/1814-4861-2023-22-4-22-33

Abstract

Introduction. The current standard of care is concurrent radiation therapy (RT) and chemotherapy with mitomycin or cisplatin in combination with fuoropyrimidine drugs. One possible option for effective chemotherapy regimens with a lower toxicity is the combination of oxaliplatin and capecitabine with RT.
The purpose of the study: a retrospective evaluation of the results of combined treatment of 74 patients with squamous cell carcinoma of the anus (SCCA) with the use of oxaliplatin and capecitabine.
Material and Methods. The study included 74 patients (men – 12.2 %, women – 87.8 %) with stage I–III SCCA. All patients underwent megavolt photon RT (2×25), a cumulative dose of 50 Gy and a boost of 10 Gy to the anal canal. From days 1 to 14 and from days 22 to 36 of RT, capecitabine was administered orally at a dose of 825 mg/m2  twice a day in combination with intravenous administration of oxaliplatin 50 mg/m2  on days 1, 8, 22, and 29 of RT. If a residual tumor 6 months after completion of chemoradiotherapy was found, patients underwent surgery.
Results. All 74 patients underwent RT with a cumulative dose of 60 Gy. Chemotherapy, according to the protocol, was completed in 58 (78.4 %) patients. Grade 3-4 toxicity was noted in 11 (14.9 %) patients. In 64 patients (86.5 %), a complete clinical response was registered. At least one late radiation side effects according to the RTOG (LENT SOMA) scale was noted in 48 (98.0 %) patients, including grade 3-4 complications in 12 (24.5 %) patients. With a median follow-up of 40 months (3-82) cumulative three-year local recurrence rate, overall and relapse-free survival were 15.3 ± 4.5 %, 73.7 ± 5.7 % and 53.5 ± 6.4 %, respectively.
Conclusion. Combined treatment of SCCA, based on the combination of RT with chemotherapy with oxaliplatin and capecitabine, is feasible and has acceptable acute toxicity. Additional clinical studies are needed using this chemotherapy regimen in combination with modern RT techniques.

About the Authors

A. A. Nevolskikh
A. Tsyb Medical Radiological Research Centre – branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russia; Obninsk Institute for Nuclear Power Engineering – National Research Nuclear University MEPHI
Russian Federation

Aleksey A. Nevolskikh, MD, DSc, Deputy Director; Professor of the Department of Surgical Diseases, 

10, Zhukov St., 249031, Obninsk;
1, Studgorodok St., 249034, Kaluga region, Obninsk



Y. Y. Mihaleva
A. Tsyb Medical Radiological Research Centre – branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russia
Russian Federation

Yulia Yu. Mihaleva, MD, Oncologist of the Department of Radiotherapy and Surgery for Abdominal Diseases, 

10, Zhukov St., 249031, Obninsk



V. A. Avdeenko
Obninsk Institute for Nuclear Power Engineering – National Research Nuclear University MEPHI
Russian Federation

Violetta A. Avdeenko, 6th year student, the Faculty of Medicine, 

1, Studgorodok St., 249034, Kaluga region, Obninsk



L. N. Titova
A. Tsyb Medical Radiological Research Centre – branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russia
Russian Federation

Lyudmila N. Titova, MD, PhD, Oncologist of the Department of Proton and Photon Therapy 

10, Zhukov St., 249031, Obninsk



T. P. Berezovskaya
A. Tsyb Medical Radiological Research Centre – branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russia
Russian Federation

Tatiana P. Berezovskaya, MD, Professor, Leading Researcher, Department of Magnetic Resonance Imaging 

10, Zhukov St., 249031, Obninsk



I. A. Gulidov
A. Tsyb Medical Radiological Research Centre – branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russia
Russian Federation

Igor A. Gulidov, MD, Professor, Head of the Department of Proton and Photon Therapy 

10, Zhukov St., 249031, Obninsk



L. O. Petrov
A. Tsyb Medical Radiological Research Centre – branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russia
Russian Federation

Leonid O. Petrov, MD, PhD, Department of Radiotherapy and Surgery for Abdominal Diseases 

10, Zhukov St., 249031, Obninsk



S. A. Ivanov
A. Tsyb Medical Radiological Research Centre – branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russia; RUDN University
Russian Federation

Sergey A. Ivanov, MD, DSc, Corresponding Member of the Russian Academy of Sciences, Director; Professor of Chair of Oncology and Radiology named after Kharchenko.
Author ID (Scopus): 16070399200 

10, Zhukov St., 249031, Obninsk;
6, Miklukho-Maklaya St., Moscow, 117198



A. D. Kaprin
RUDN University; P.A. Hertsen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russia; National Medical Research Radiological Centre of the Ministry of Health of the Russia
Russian Federation

Andrej D. Kaprin, MD, Professor, Academician of the Russian Academy of Sciences, Chief Oncologist of the Russian Federation, Head of Chair of Oncology and Radiology named after Kharchenko; Director; Director General, 

6, Miklukho-Maklaya St., 117198, Moscow;
3, 2nd Botkinsky proezd, 125284, Moscow;
4, Koroleva St., 249036, Obninsk



References

1. Siegel R.L., Miller K.D., Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020; 70(1): 7–30. doi: 10.3322/caac.21590.

2. Morton M., Melnitchouk N., Bleday R. Squamous cell carcinoma of the anal canal. Curr Probl Cancer. 2018; 42(5): 486–92. doi: 10.1016/j.currproblcancer.2018.11.001.

3. Gordeev S.S., Rasulov A,O.,Nazarenko A.V., Tkachev S.I., Suraeva Y.E., Fedyanin M.Y. Squamous cell carcinoma of the anal canal as a rare disease: preciousbreed. Journal of N. N. Blokhin Russian Cancer Research Center RAMS. 2015; 26(2): 5–14. (in Russian).

4. Malignant tumors in Russia in 2020 (morbidity and mortality). Ed. by A.D. Kaprin, V.V. Starinsky, A.O. Shakhzadova. Moscow, 2021. 250 p. (in Russian).

5. Leeds I.L., Fang S.H. Anal cancer and intraepithelial neoplasia screening: A review. World J. Gastrointest Surg. 2016; 27; 8(1): 41–51. doi: 10.4240/wjgs.v8.i1.41.

6. Walhart T. Human Papillomavirus Biology, Pathogenesis, and Potential for Drug Discovery: A Literature Review for HIV Nurse Clinical Scientists. J. Assoc. Nurses AIDS Care. 2015; 26(6): 693–702. doi: 10.1016/j.jana.2015.07.001.

7. Gupta S.M., Mania-Pramanik J. Retraction Note: Molecular mechanisms in progression of HPV-associated cervical carcinogenesis. J Biomed Sci. 2019; 26(1): 50. doi: 10.1186/s12929-019-0545-6.

8. Bodily J., Laimins L.A. Persistence of human papillomavirus infection: keys to malignant progression. Trends Microbiol. 2011; 19(1): 33–9. doi: 10.1016/j.tim.2010.10.002.

9. National Comprehensive Cancer Network [Internet]. NCCN Clinical Practice Guidelines in Oncology: Anal Carcinoma (Version 2.2022 – September 2, 2022). URL: http://www.nccn.org [cited 2022 Oct 16].

10. Clinical guidelines [Internet]. Squamous cell carcinoma of the anal canal, anal margin, perianal skin. (in Russian). URL: https://cr.minzdrav.gov.ru/recomend/555_2 [cited 2023 Mar 1].

11. Ajani J.A., Winter K.A., Gunderson L.L., Pedersen J., Benson A.B., Thomas C.R., Mayer R.J., Haddock M.G., Rich T.A., Willett C. Fluorouracil, mitomycin, and radiotherapy vs fuorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial. JAMA. 2008; 299(16): 1914–21. doi: 10.1001/jama.299.16.1914.

12. James R.D., Glynne-Jones R., Meadows H.M., Cunningham D., Myint A.S., Saunders M.P., Maughan T., McDonald A., Essapen S., Leslie M., Falk S., Wilson C., Gollins S., Begum R., Ledermann J., Kadalayil L., Sebag-Montefore D. 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. doi: 10.1016/S1470-2045-(13)70086-X.

13. Jones C.M., Adams R., Downing A., Glynne-Jones R., Harrison M., Hawkins M., Sebag-Montefore D., Gilbert D.C., Muirhead R. Toxicity, Tolerability, and Compliance of Concurrent Capecitabine or 5-Fluorouracil in Radical Management of Anal Cancer With Single-dose Mitomycin-C and Intensity Modulated Radiation Therapy: Evaluation of a National Cohort. Int J Radiat Oncol Biol Phys. 2018; 101(5): 1202–11. doi: 10.1016/j.ijrobp.2018.04.033.

14. Glynne-Jones R., Meadows H., Wan S., Gollins S., Leslie M., Levine E., McDonald A.C., Myint S., Samuel L., Sebag-Montefore D.; National Cancer Research Institute Anal Sub Group 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 C in anal cancer. Int J Radiat Oncol Biol Phys. 2008; 72(1): 119–26. doi: 10.1016/j.ijrobp.2007.12.012.

15. Deenen M.J., Dewit L., Boot H., Beijnen J.H., Schellens J.H., 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 Radiat Oncol Biol Phys. 2013; 85(5): 201–7. doi: 10.1016/j.ijrobp.2012.12.008.

16. Eng C., Jácome A.A., Das P., Chang G.J., RodriguezBigas M., Skibber J.M., Wolff R.A., Qiao W., Xing Y., Sethi S., Ohinata A., Crane C.H. A Phase II Study of Capecitabine/Oxaliplatin With Concurrent Radiotherapy in Locally Advanced Squamous Cell Carcinoma of the Anal Canal. Clin Colorectal Cancer. 2019; 18(4): 301–6. doi: 10.1016/j.clcc.2019.06.003.

17. Cox J.D., Stetz J., Pajak T.F. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys. 1995; 31(5): 1341–6. doi: 10.1016/0360-3016(95)00060-C.

18. LENT SOMA tables table of contents. Radiother Oncol. 1995; 35(1): 17–60. https://doi.org/10.1016/0167-8140(95)90055-1.

19. Northover J., GlynneJones R., Sebag-Montefiore D., James R., Meadows H., Wan S., Jitlal M., Ledermann J. Chemoradiation for the treatment of epidermoid anal cancer: 13year follow up of the frst randomised UKCCCR Anal Cancer Trial (ACT I). Br J Cancer. 2010; 102(7): 1123–8. doi: 10.1038/sj.bjc.6605605.

20. Flam M., John M., Pajak T.F., Petrelli N., Myerson R., Doggett S., Quivey J., Rotman M., Kerman H., Coia L., Murray K. Role of mitomycin in combination with fuorouracil and radiotherapy, and of salvage chemoradiation in the defnitive 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. doi: 10.1200/JCO.1996.14.9.2527.

21. Bartelink H., Roelofsen F., Eschwege F., Rougier P., Bosset J.F., Gonzalez D.G., Peiffert D., van Glabbeke M., Pierart M. 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. doi: 10.1200/JCO.1997.15.5.2040.

22. Peiffert D., Tournier-Rangeard L., Gérard J.P., Lemanski C., François E., Giovannini M., Cvitkovic F., Mirabel X., Bouché O., Luporsi E., Conroy T., Montoto-Grillot C., Mornex F., Lusinchi A., Hannoun-Lévi J.M., Seitz J.F., Adenis A., Hennequin C., Denis B., Ducreux M. Induction chemotherapy and dose intensifcation of the radiation boost in locally advanced anal canal carcinoma: fnal analysis of the randomized UNICANCER ACCORD 03 trial. J Clin Oncol. 2012; 30(16): 1941–8. doi: 10.1200/JCO.2011.35.4837. Erratum in: J Clin Oncol. 2012; 30(31): 3903.

23. Clinical guidelines [Internet]. Cancer of the esophagus and cardia. URL: https://cr.minzdrav.gov.ru/recomend/237_5 [cited 2023 Mar 1].

24. Clinical guidelines [Internet]. Cervical cancer.. URL: https://cr.minzdrav.gov.ru/recomend/537_1 [cited 2023 Mar 1].

25. Rao S., Sclafani F., Eng C., Adams R.A., Guren M.G., Sebag-Montefore D., Benson A., Bryant A., Peckitt C., Segelov E., Roy A., Seymour M.T., Welch J., Saunders M.P., Muirhead R., O’Dwyer P., Bridgewater J., Bhide S., Glynne-Jones R., Arnold D., Cunningham D. International Rare Cancers Initiative Multicenter Randomized Phase II Trial of Cisplatin and Fluorouracil Versus Carboplatin and Paclitaxel in Advanced Anal Cancer: InterAAct. J Clin Oncol. 2020; 38(22): 2510–8. doi: 10.1200/JCO.19.03266.

26. Gunderson L.L., Moughan J., Ajani J.A., Pedersen J.E., Winter K.A., Benson A.B., Thomas C.R., Mayer R.J., Haddock M.G., Rich T.A., Willett C.G. Anal carcinoma: impact of TN category of disease on survival, disease relapse, and colostomy failure in US Gastrointestinal Intergroup RTOG 98-11 phase 3 trial. Int J Radiat Oncol Biol Phys. 2013; 87(4): 638–45. doi: 10.1016/j.ijrobp.2013.07.035.

27. Meulendijks D., Dewit L., Tomasoa N.B., van Tinteren H., Beijnen J.H., Schellens J.H., Cats A. Chemoradiotherapy with capecitabine for locally advanced anal carcinoma: an alternative treatment option. Br J Cancer. 2014; 111(9): 1726–33. doi: 10.1038/bjc.2014.467.


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Nevolskikh A.A., Mihaleva Y.Y., Avdeenko V.A., Titova L.N., Berezovskaya T.P., Gulidov I.A., Petrov L.O., Ivanov S.A., Kaprin A.D. Immediate and long-term results of radiation therapy in combination with capecitabine and oxaliplatin in the treatment of patients with asquamous cell carcinoma of the anus. Siberian journal of oncology. 2023;22(4):22-33. (In Russ.) https://doi.org/10.21294/1814-4861-2023-22-4-22-33

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ISSN 1814-4861 (Print)
ISSN 2312-3168 (Online)