Assessment of Gemcitabine as Chemoradiotherapy in Patients With Locally Advanced Carcinoma of Cervix and Renal Disease

Summary

From the global burden of Cervical Cancer (CC), 85% occurs in developing countries, representing 12% of cancer in women. In Mexico CC ranks second in incidence and mortality among women. The National Institute of Cancer in Mexico (lNCAN) receives annually about 500 patients with CC, 80% of which are diagnosed with locally advanced disease. Furthermore, 10 to 20% of these present kidney deterioration. The main reason for kidney disease is ureteral obstruction, other causes include age and comorbidities, such as diabetes and hypertension. The standard treatment for locally advanced disease consists in concomitant chemo-radiotherapy based on cisplatin (QT-RT), followed by brachytherapy, with an absolute benefit of 10%. However, the use of cisplatin in patients with renal disease may be questionable, considering it is a nephrotoxic treatment. Given that renal dysfunction limits the standard treatment efficiency because of the widely known nephrotoxicity of cisplatin, in most Cancer Centers of our country, patients with renal dysfunction receive only radiation therapy, even though it has proven less effective than concomitant QT-RT, limiting disease-free and overall survival of these patients. Venook et al. used gemcitabine as a radiosensitizer in patients with cancer and renal dysfunction. Our group, has observed encouraging results using gemcitabine as an alternative to cisplatin in concomitant treatment with radiotherapy, in CC patients with renal insufficiency. 89% of patients had complete response and improvement in renal function, with an enhanced creatinine clearance after treatment. Therefore, it is necessary to explore the safety of gemcitabine as an alternative treatment for CC patients with locally advanced disease and renal deterioration. We propose this clinical trial to assess the safety of treatment with gemcitabine and specifically on renal function in patients with renal deterioration. It is important to take into consideration that CC in advanced stages produces pain, transvaginal fetid discharge and general discomfort. It also causes side effects secondary to renal failure such as nausea, vomiting, fatigue, anemia, among others. These effects have a significant impact on the quality of life of these patients. Cancer treatment and its side effects, besides the implications of a nephrostomy catheter or ileostomy bag, determine the deterioration in the quality of life of the patient, during and sometimes after treatment. Thus it is of utmost importance to evaluate the factors that could help improve the quality of life of patients and explore the factors that deteriorate it. This clinical trial aims to generate scientific evidence to help make the best decisions concerning the treatment of patients with cervical cancer and renal impairment, and the impact on their quality of life.

Timeline

Start

2018-01-16

Primary completion

2025-07-01

Completion

2025-11-01

Publications

• Background Green JA, Kirwan JM, Tierney JF, Symonds P, Fresco L, Collingwood M, Williams CJ. Survival and recurrence after concomitant chemotherapy and radiotherapy for cancer of the uterine cervix: a systematic review and meta-analysis. Lancet. 2001 Sep 8;358(9284):781-6. doi: 10.1016/S0140-6736(01)05965-7.
• Background Candelaria M, Chanona-Vilchis J, Cetina L, Flores-Estrada D, Lopez-Graniel C, Gonzalez-Enciso A, Cantu D, Poitevin A, Rivera L, Hinojosa J, de la Garza J, Duenas-Gonzalez A. Prognostic significance of pathological response after neoadjuvant chemotherapy or chemoradiation for locally advanced cervical carcinoma. Int Semin Surg Oncol. 2006 Feb 3;3:3. doi: 10.1186/1477-7800-3-3.
• Background Zarba JJ, Jaremtchuk AV, Gonzalez Jazey P, Keropian M, Castagnino R, Mina C, Arroyo G; GETICS (Grupo de Estudio, Tratamiento e Investigacion del Cancer del Sur) Argentina. A phase I-II study of weekly cisplatin and gemcitabine with concurrent radiotherapy in locally advanced cervical carcinoma. Ann Oncol. 2003 Aug;14(8):1285-90. doi: 10.1093/annonc/mdg345.
• Background Duenas-Gonzalez A, Lopez-Graniel C, Gonzalez A, Reyes M, Mota A, Munoz D, Solorza G, Hinojosa LM, Guadarrama R, Florentino R, Mohar A, Melendez J, Maldonado V, Chanona J, Robles E, De la Garza J. A phase II study of gemcitabine and cisplatin combination as induction chemotherapy for untreated locally advanced cervical carcinoma. Ann Oncol. 2001 Apr;12(4):541-7. doi: 10.1023/a:1011117617514.
• Background Chang PY, Dai MS, Ho CL, Yao NS. Administration of gemcitabine and cisplatin in cancer patients with renal failure under hemodialysis. J BUON. 2013 Oct-Dec;18(4):1058-61.
• Background Pattaranutaporn P, Thirapakawong C, Chansilpa Y, Therasakvichya S, Ieumwananontachai N, Thephamongkhol K. Phase II study of concurrent gemcitabine and radiotherapy in locally advanced stage IIIB cervical carcinoma. Gynecol Oncol. 2001 Jun;81(3):404-7. doi: 10.1006/gyno.2001.6197.
• Background Bosch A, Frias Z, Valda GC. Prognostic significance of ureteral obstruction in carcinoma of the cervix uteri. Acta Radiol Ther Phys Biol. 1973 Feb;12(1):47-56. doi: 10.3109/02841867309131091. No abstract available.
• Background Cetina L, Rivera L, Candelaria M, de la Garza J, Duenas-Gonzalez A. Chemoradiation with gemcitabine for cervical cancer in patients with renal failure. Anticancer Drugs. 2004 Sep;15(8):761-6. doi: 10.1097/00001813-200409000-00004.
• Background Rose PG, Ali S, Whitney CW, Lanciano R, Stehman FB. Impact of hydronephrosis on outcome of stage IIIB cervical cancer patients with disease limited to the pelvis, treated with radiation and concurrent chemotherapy: a Gynecologic Oncology Group study. Gynecol Oncol. 2010 May;117(2):270-5. doi: 10.1016/j.ygyno.2010.01.045. Epub 2010 Feb 24.
• Background Tomimaru Y, Eguchi H, Satoh T, Tomokuni A, Asaoka T, Wada H, Marubashi S, Ogawa K, Takehara T, Mori M, Doki Y, Nagano H. Feasibility of pre-operative chemoradiotherapy with gemcitabine to treat pancreatic cancer in patients with impaired renal function. Jpn J Clin Oncol. 2015 Apr;45(4):343-8. doi: 10.1093/jjco/hyu224. Epub 2015 Jan 14.
• Background Venook AP, Egorin MJ, Rosner GL, Hollis D, Mani S, Hawkins M, Byrd J, Hohl R, Budman D, Meropol NJ, Ratain MJ. Phase I and pharmacokinetic trial of gemcitabine in patients with hepatic or renal dysfunction: Cancer and Leukemia Group B 9565. J Clin Oncol. 2000 Jul;18(14):2780-7. doi: 10.1200/JCO.2000.18.14.2780.
• Background Tanji N, Fukumoto T, Miura N, Yanagihara Y, Shirato A, Azuma K, Miyauchi Y, Kikugawa T, Shimamoto K, Yokoyama M. Combined chemotherapy with gemcitabine and carboplatin for metastatic urothelial carcinomas in patients with high renal insufficiency. Int J Clin Oncol. 2013 Oct;18(5):910-5. doi: 10.1007/s10147-012-0466-9. Epub 2012 Aug 31.
• Background Grigsby PW. Cervical cancer: combined modality therapy. Cancer J. 2001 Jul-Aug;7 Suppl 1:S47-50.
• Background Zahra MA, Taylor A, Mould G, Coles C, Crawford R, Tan LT. Concurrent weekly cisplatin chemotherapy and radiotherapy in a haemodialysis patient with locally advanced cervix cancer. Clin Oncol (R Coll Radiol). 2008 Feb;20(1):6-11. doi: 10.1016/j.clon.2007.10.007. Epub 2008 Jan 11.

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