Radiotherapy and 5-fluorouracil-cisplatin treatment for high-risk uterine cervical cancer

Radioterapia y 5-fluorouracilo-cisplatino en el tratamiento del cáncer de cuello uterino de alto riesgo

Objective: to evaluate the efficacy of radiotherapy combined with 5-fluorouracil-cisplatin in the treatment of high-risk uterine cervical cancer. Materials and methods: Retrospective study, in which the data of patients treated between January 2009 and December 2019 at Hospital Central “Dr. Urquinaona”, Maracaibo, Venezuela, was analyzed. The clinical records of all patients who underwent radical hysterectomy and bilateral pelvic lymphadenectomy and received adjuvant concurrent chemoradiotherapy with 5-fluorouracil-cisplatin (treatment group) compared with those patients not managed with this regimen, those who did not receive any adjuvant treatment or received only radiotherapy (control group), were reviewed. The general characteristics, treatment adverse effects, disease recurrences and survival rate were evaluated. Results: 164 patients remained for the final analysis, of which 115 (70.1%) were in the treatment group and 49 (29.9%) in the control group. No statistically significant differences were found in the clinical characteristics of patients between the two groups (p = ns); while differences in the distant recurrence rate (p = 0.0056) were found. Progression-free survival and overall survival in both groups did not show significant differences (p = 0.2678 and p = 0.3452). Conclusion: there is no evident benefit of the use of 5-fluorouracil-cisplatin in terms of progression or overall survival in patients with high-risk cervical carcinoma.

1. Galceran J, Ameijide A, Carulla M, Mateos A, Quirós JR, Rojas D, Alemán A, Torrella A, Chico M, Vicente M, Díaz JM, Larrañaga N, Marcos-Gragera R, Sánchez MJ, Perucha J, Franch P, Navarro C, Ardanaz E, Bigorra J, Rodrigo P, Bonet RP; REDECAN Working Group. Cancer incidence in Spain, 2015. Clin Transl Oncol. 2017;19(7):799-825. doi: 10.1007/s12094-016-1607-9.
2. Global Burden of Disease Cancer Collaboration, Fitzmaurice C, Allen C, Barber RM, Barregard L, Bhutta ZA, Brenner H. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: A systematic analysis for the global burden of disease study. JAMA Oncol. 2017;3(4):524-548. doi: 10.1001/jamaoncol.2016.5688.
3. Kokka F, Bryant A, Brockbank E, Powell M, Oram D. Hysterectomy with radiotherapy or chemotherapy or both for women with locally advanced cervical cancer. Cochrane Database Syst Rev. 2015;(4):CD010260. doi: 10.1002/14651858.CD010260.pub2.
4. Fregnani JH, de Oliveira Latorre Mdo R, Novik PR, Lopes A, de Oliveira JC, Tsunoda AT, Soares FA. Extent of pelvic lymphadenectomy in women with squamous cell carcinoma of the uterine cervix: is there any prognostic value? J Surg Oncol. 2009;100(3):252-7. doi: 10.1002/jso.21252.
5. Brambs CE, Höhn AK, Hentschel B, Fischer U, Bilek K, Horn LC. The prognostic impact of grading in FIGO IB and IIB squamous cell cervical carcinomas. Geburtshilfe Frauenheilkd. 2019;79(2):198-204. doi: 10.1055/a-0828-7681.
6. Trudel M, Merlot B, Dedet B, Faye N, Kerdraon O, Vinatier D, Collinet P. Is radical hysterectomy necessary in surgical procedure for early stage cervical cancer? Gynecol Obstet Fertil. 2013;41(12):715-21. doi: 10.1016/j.gyobfe.2013.10.002.
7. Sakakibara A, Matsui K, Katayama T, Higuchi T, Terakawa K, Konishi I. Age-related survival disparity in stage IB and IIB cervical cancer patients. J Obstet Gynaecol Res. 2019;45(3):686-694. doi: 10.1111/jog.13891.
8. Liu MT, Hsu JC, Liu WS, Wang AY, Huang WT, Chang TH, Pi CP, Huang CY, Huang CC, Chou PH, Chen TH. Prognostic factors affecting the outcome of early cervical cancer treated with radical hysterectomy and post-operative adjuvant therapy. Eur J Cancer Care (Engl). 2008;17(2):174-81. doi: 10.1111/j.1365-2354.2007.00831.x.
9. Chen L, Lü WG, Xie X, Chen HZ, Yu H, Ni XH. Analysis of prognostic factors in patients with cervical squamous cell carcinoma of stage Ib and IIa. Zhonghua Fu Chan Ke Za Zhi. 2005;40(4):239-42.
10. Rotman M, Sedlis A, Piedmonte MR, Bundy B, Lentz SS, Muderspach LI, Zaino RJ. A phase III randomized trial of postoperative pelvic irradiation in Stage IB cervical carcinoma with poor prognostic features: follow-up of a gynecologic oncology group study. Int J Radiat Oncol Biol Phys. 2006;65(1):169-76.
11. Lee JW, Kim BG, Lee SJ, Lee SH, Park CS, Lee JH, Huh SJ, Bae DS. Preliminary results of consolidation chemotherapy following concurrent chemoradiation after radical surgery in high-risk early-stage carcinoma of the uterine cervix. Clin Oncol (R Coll Radiol). 2005;17(6):412-7. doi: 10.1016/j.clon.2005.02.006
12. Sartori E, Tisi G, Chiudinelli F, La Face B, Franzini R, Pecorelli S. Early stage cervical cancer: adjuvant treatment in negative lymph node cases. Gynecol Oncol. 2007;107(1 Suppl 1):S170-4. doi: 10.1016/j.ygyno.2007.07.026
13. Rushdan MN, Tay EH, Khoo-Tan HS, Lee KM, Low JH, Ho TH, Yam KL. Tailoring the field and indication of adjuvant pelvic radiation for patients with FIGO stage Ib lymph nodes-negative cervical carcinoma following radical surgery based on the GOG score--a pilot study. Ann Acad Med Singapore. 2004;33(4):467-72.
14. Mabuchi S, Morishige K, Isohashi F, Yoshioka Y, Takeda T, Yamamoto T, Yoshino K, Enomoto T, Inoue T, Kimura T. Postoperative concurrent nedaplatin-based chemoradiotherapy improves survival in early-stage cervical cancer patients with adverse risk factors. Gynecol Oncol. 2009;115(3):482-7. doi: 10.1016/j.ygyno.2009.09.002.
15. Reichert ZR, Wahl DR, Morgan MA. Translation of targeted radiation sensitizers into clinical trials. Semin Radiat Oncol. 2016;26(4):261-70. doi: 10.1016/j.semradonc.2016.06.001.
16. Petrelli F, De Stefani A, Raspagliesi F, Lorusso D, Barni S. Radiotherapy with concurrent cisplatin-based doublet or weekly cisplatin for cervical cancer: a systematic review and meta-analysis. Gynecol Oncol. 2014;134(1):166-71. doi: 10.1016/j.ygyno.2014.04.049.
17. Stehman FB, Ali S, Keys HM, Muderspach LI, Chafe WE, Gallup DG, Walker JL, Gersell D. Radiation therapy with or without weekly cisplatin for bulky stage 1B cervical carcinoma: follow-up of a Gynecologic Oncology Group trial. Am J Obstet Gynecol. 2007;197(5):503.e1-6. doi: 10.1016/j.ajog.2007.08.003
18. Cheewakriangkrai C, Srisomboon J, Chitapanarux I, Suprasert P, Phongnarisorn C, Siriaree S, Charoenkwan K. Concurrent cisplatin-based chemoradiation and adjuvant hysterectomy for bulky stage IB-IIA cervical cancer. J Med Assoc Thai. 2005;88(10):1331-7.
19. Valdes G, Iwamoto KS. Re-evaluation of cellular radiosensitization by 5-fluorouracil: high-dose, pulsed administration is effective and preferable to conventional low-dose, chronic administration. Int J Radiat Biol. 2013;89(10):851-62. doi: 10.3109/09553002.2013.797620.
20. Liu JL, Huang WS, Lee KC, Tung SY, Chen CN, Chang SF. Effect of 5-fluorouracil on excision repair cross-complementing 1 expression and consequent cytotoxicity regulation in human gastric cancer cells. J Cell Biochem. 2018;119(10):8472-8480. doi: 10.1002/jcb.27073.
21. Matsuo K, Shimada M, Aoki Y, Sakamoto M, Takeshima N, Fujiwara H, Matsumoto T, Mikami M, Sugiyama T. Comparison of adjuvant therapy for node-positive clinical stage IB-IIB cervical cancer: Systemic chemotherapy versus pelvic irradiation. Int J Cancer. 2017;141(5):1042-1051. doi: 10.1002/ijc.30793.
22. Eifel PJ, Winter K, Morris M, Levenback C, Grigsby PW, Cooper J, Rotman M, Gershenson D, Mutch DG. Pelvic irradiation with concurrent chemotherapy versus pelvic and para-aortic irradiation for high-risk cervical cancer: an update of radiation therapy oncology group trial (RTOG) 90-01. J Clin Oncol. 2004;22(5):872-80.
23. Datta NR, Stutz E, Liu M, Rogers S, Klingbiel D, Siebenhüner A, Singh S, Bodis S. Concurrent chemoradiotherapy vs. radiotherapy alone in locally advanced cervix cancer: A systematic review and meta-analysis. Gynecol Oncol. 2017;145(2):374-385. doi: 10.1016/j.ygyno.2017.01.033.
24. Tangjitgamol S, Katanyoo K, Laopaiboon M, Lumbiganon P, Manusirivithaya S, Supawattanabodee B. Adjuvant chemotherapy after concurrent chemoradiation for locally advanced cervical cancer. Cochrane Database Syst Rev. 2014;(12):CD010401. doi: 10.1002/14651858.CD010401.pub2.
25. Monk BJ, Wang J, Im S, Stock RJ, Peters WA 3rd, Liu PY, Barrett RJ 2nd, Berek JS, Souhami L, Grigsby PW, Gordon W Jr, Alberts DS; Gynecologic Oncology Group; Southwest Oncology Group; Radiation Therapy Oncology Group. Rethinking the use of radiation and chemotherapy after radical hysterectomy: a clinical-pathologic analysis of a Gynecologic Oncology Group/Southwest Oncology Group/Radiation Therapy Oncology Group trial. Gynecol Oncol. 2005;96(3):721-8. doi: 10.1016/j.ygyno.2004.11.007