Treatment outcome analysis of chemotherapy combined with modulated electro-hyperthermia compared with chemotherapy alone for recurrent cervical cancer, following irradiation

Lee,Sun  Young; Lee,Na  Ri; Cho,Dong‑Hyu; Kim,Jung  Soo

doi:10.3892/ol.2017.6117

Treatment outcome analysis of chemotherapy combined with modulated electro-hyperthermia compared with chemotherapy alone for recurrent cervical cancer, following irradiation

Authors:
- Sun Young Lee
- Na Ri Lee
- Dong‑Hyu Cho
- Jung Soo Kim
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Affiliations: Department of Radiation Oncology, Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju, Jeollabukdo 561‑712, Republic of Korea, Institute of Clinical Medicine, Chonbuk National University‑Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Jeollabukdo 561‑712, Republic of Korea
Published online on: May 4, 2017 https://doi.org/10.3892/ol.2017.6117
Pages: 73-78
Copyright: © Lee et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The survival of patients with recurrent cervical cancer following irradiation remains poor. Chemotherapy combined with hyperthermia has been demonstrated to improve the response rate. The present study was performed to evaluate the effect of modulated electro‑hyperthermia combined with conventional chemotherapy compared with chemotherapy alone on recurrent cervical cancer previously treated with irradiation. A total of 20 patients were treated with chemotherapy alone, and 18 were treated with chemotherapy combined with modulated electro‑hyperthermia. A single patient was treated with chemo‑radiotherapy as primary treatment and then relapsed; the tumor was inoperable and radio‑refractory upon recurrence. Local metastases, including metastasis of the para‑aortic lymph nodes and adjacent pelvic lymph nodes were included, but distant metastases were excluded. Modulated electro‑hyperthermia was performed three times per week beginning at chemotherapy initiation, and patients underwent a total of 36 sessions. The overall response (complete remission + partial remission + stable disease/progressive disease) to treatment was significantly greater in the group of patients who underwent chemotherapy combined with modulated electro‑hyperthermia (P=0.0461), and at the evaluation conducted at the last follow‑up visit, the response rate was significantly higher (P=0.0218). Additionally, severe complications were not reported. In the present study, of patients with recurrent cervical cancer previously treated with irradiation, the overall response rate for patients treated with chemotherapy combined with modulated electro-hyperthermia was significantly greater than that for those treated with chemotherapy alone.

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1	International Agency for Research on Cancer, . World Health OrganizationLatest world cancer statistics. IARC; Lyon: 2013
2	American Society of Clinical Oncology (ASCO), . Cervical cancer: Statistics. http://www.cancer.net/cancer-types/cervical-cancer/statistics
3	Korean statistical information service, . Statistics Korea. Statistics Korea, Daejeon. 2012, http://kosis.kr
4	Seol HJ, Ki KD and Lee JM: Epidemiologic characteristics of cervical cancer in Korean women. J Gynecol Oncol. 25:70–74. 2014. View Article : Google Scholar : PubMed/NCBI
5	Kuo DY, Blank SV, Christos PJ, Kim M, Caputo TA, Pothuri B, Hershman D, Goldman N, Ivy PS, Runowicz CD, et al: Paclitaxel plus oxaliplatin for recurrent or metastatic cervical cancer: A New York cancer consortium study. Gynecol Oncol. 116:442–446. 2010. View Article : Google Scholar : PubMed/NCBI
6	de Wit R, van der Zee J, van der Burg ME, Kruit WH, Logmans A, van Rhoon GC and Verweij J: A phase I/II study of combined weekly systemic cisplatin and locoregional hyperthermia in patients with previously irradiated recurrent carcinoma of the uterine cervix. Br J Cancer. 80:1387–1391. 1999. View Article : Google Scholar : PubMed/NCBI
7	Rietbroek RC, Schilthuis MS, Bakker PJ, van Dijk JD, Postma AJ, González González D, Bakker AJ, van der Velden J, Helmerhorst TJ and Veenhof CH: Phase II trial of weekly locoregional hyperthermia and cisplatin in patients with a previously irradiated recurrent carcinoma of the uterine cervix. Cancer. 79:935–943. 1997. View Article : Google Scholar : PubMed/NCBI
8	Jones EL, Samulski TV, Dewhirst MW, Alvarez-Secord A, Berchuck A, Clarke-Pearson D, Havrilesky LJ, Soper J and Prosnitz LR: A pilot phase II trial of concurrent radiotherapy, chemotherapy, and hyperthermia for locally advanced cervical carcinoma. Cancer. 98:277–282. 2003. View Article : Google Scholar : PubMed/NCBI
9	Tsuda H, Tanaka M, Manabe T, Ikeda H, Negoro S, Ishiko O and Yamamoto K: Phase I study of combined radiation, hyperthermia and intra-arterial carboplatin for local recurrence of cervical cancer. Ann Oncol. 14:298–303. 2003. View Article : Google Scholar : PubMed/NCBI
10	Westermann AM, Jones EL, Schem BC, van der Steen-Banasik EM, Koper P, Mella O, Uitterhoeve AL, de Wit R, van der Velden J, Burger C, et al: First results of triple-modality treatment combining radiotherapy, chemotherapy, and hyperthermia for the treatment of patients with stage IIB III, and IVA cervical carcinoma. Cancer. 104:763–770. 2005. View Article : Google Scholar : PubMed/NCBI
11	Franckena M, de Wit R, Ansink AC, Notenboom A, Canters RA, Fatehi D, Van Rhoon GC and Van Der Zee J: Weekly systemic cisplatin plus locoregional hyperthermia: An effective treatment for patients with recurrent cervical carcinoma in a previously irradiated area. Int J Hyperthermia. 23:443–450. 2007. View Article : Google Scholar : PubMed/NCBI
12	Dahl O: Interaction of heat and drugs in vitro and in vivoThermoradiotherapy and Thermochemotherapy. Seegenschmiedt MH, Fessenden P and Vernon CC: 1. Springer Verlag; Berlin: pp. 103–121. 1995, View Article : Google Scholar
13	Hegyi G, Szigeti GP and Szász A: Hyperthermia versus oncothermia: Cellular effects in complementary cancer therapy. Evid Based Complement Alternat Med. 2013:6728732013. View Article : Google Scholar : PubMed/NCBI
14	Andocs G, Okamoto Y, Kawamoto K, Osaki T, Tsuka T, Imagawa T, Minami S, Balogh L, Meggyeshazi N and Szasz O: Oncothermia basic research at in vivo level: The first results in Japan. Conference Papers Med. 2013:pp. 1973282013;
15	Szasz A, Vincze G, Szasz O and Szasz N: An energy analysis of extracellular hyperthermia. Electromagn Biol Med. 22:103–115. 2003. View Article : Google Scholar
16	Meggyeshazi N, Andocs G, Balogh L, Balla P, Kiszner G, Teleki I, Jeney A and Krenacs T: DNA fragmentation and caspase-independent programmed cell death by modulated electrohyperthermia. Strahlenther Onkol. 190:815–822. 2014. View Article : Google Scholar : PubMed/NCBI
17	Andocs G, Meggyeshazi N, Balogh L, Spisak S, Maros ME, Balla P, Kiszner G, Teleki I, Kovago C and Krenacs T: Upregulation of heat shock proteins and the promotion of damage associated molecular pattern signals in a colorectal cancer model by modulated electro-hyperthermia. Cell Stress Chaperones. 20:37–46. 2014. View Article : Google Scholar : PubMed/NCBI
18	Szasz A: Challenges and solutions in oncological hyperthermia. Med. 29:1–23. 2013.
19	Fiorentini G, Giovanis P, Rossi S, Dentico P, Paola R, Turrisi G and Bernardeschi P: A phase II clinical study on relapsed malignant gliomas treated with electro-hyperthermia. In Vivo. 20:721–724. 2006.PubMed/NCBI
20	Hager ED, Sahinbas H, Groenemeyer DH and Migeod F: Prospective phase II trial for recurrent high-grade malignant gliomas with capacitive coupled low radiofrequency (LRF) deep hyperthermia. J Clin Oncol. 26:20472008. View Article : Google Scholar
21	Sahinbas H, Grönemeyer DH, Böcher E and Szasz A: Retrospective clinical study of adjuvant electro-hyperthermia treatment for advanced brain-gliomas. Dtsch Z Onkol. 39:154–160. 2007. View Article : Google Scholar
22	Wismeth C, Dudel C, Pascher C, Ramm P, Pietsch T, Hirschmann B, Reinert C, Proescholdt M, Rümmele P, Schuierer G, et al: Transcranial electro-hyperthermia combined with alkylating chemotherapy in patients with relapsed high-grade gliomas: Phase I clinical results. J Neurooncol. 98:395–405. 2010. View Article : Google Scholar : PubMed/NCBI
23	Andocs G, Szasz O and Szasz A: Oncothermia treatment of cancer: From the laboratory to clinic. Electromagn Biol Med. 28:148–165. 2009. View Article : Google Scholar : PubMed/NCBI
24	Szasz A: Current status of oncothermia therapy for Lung cancer. Korean J Thorac Cardiovasc Surg. 47:77–93. 2014. View Article : Google Scholar : PubMed/NCBI
25	Jeung TS, Ma SY, Yu J and Lim S: Cases that respond to Oncothermia Monotherapy. Conference Papers Med. 2013:pp. 3924802013;
26	Szasz A, Iluri N and Szasz O: Local hyperthermia in oncology-to choose or not to choose?Hyperthermia. Huilgol N: InTech; Croatia: pp. 1–82. 2013
27	Gonzalez-Gonzalez D: Thermo-radiotherapy for tumors of the lower gastro-instenstinal tractThermoradiotherapy and thermochemiotherapy: Biology, physiology, physics. Seegenschmiedt MH, Fessenden P and Vernon CC: Springer Verlag; Berlin: pp. 105–109. 1996, View Article : Google Scholar
28	Brader KR, Morris M, Levenback C, Levy L, Lucas KR and Gershenson DM: Chemotherapy for cervical carcinoma: Factors determining response and implications for clinical trial design. J Clin Oncol. 16:1879–1884. 1998. View Article : Google Scholar : PubMed/NCBI
29	Potter ME, Hatch KD, Potter MY, Shingleton HM and Baker VV: Factors affecting the response of recurrent squamous cell carcinoma of the cervix to cisplatin. Cancer. 63:1283–1286. 1989. View Article : Google Scholar : PubMed/NCBI
30	Green DM, Burton GV, Cox EB, Hanson D, Moore J and Oleson JR: A phase I/II study of combined cisplatin and hyperthermia treatment for refractory malignancy. Int J Hyperthermia. 5:13–21. 1989. View Article : Google Scholar : PubMed/NCBI
31	Song CW: Effect of local hyperthermia on blood flow and microenvironment: A review. Cancer Res. 44 10 Suppl:4721s–4730s. 1984.PubMed/NCBI
32	Hegyi G, Vincze G and Szasz A: On the dynamic equilibrium in homeostasis. Open J Biophys. 2:64–71. 2012. View Article : Google Scholar
33	Urano M, Kuroda M and Nishimura Y: For the clinical application of thermochemotherapy given at mild temperatures. Int J Hyperthermia. 15:79–107. 1999. View Article : Google Scholar : PubMed/NCBI
34	Urano M, Wong KH, Reynolds R and Begley J: The advantageous use of hypoxic tumour cells in cancer therapy: Identical chemosensitization by metronidazole and misonidazole at moderately elevated temperatures. Int J Hyperthermia. 11:379–388. 1995. View Article : Google Scholar : PubMed/NCBI
35	Heijkoop ST, van Doorn HC, Stalpers LJ, Boere IA, van der Velden J, Franckena M and Westermann AM: Results of concurrent chemotherapy and hyperthermia in patients with recurrent cervical cancer after previous chemoradiation. Int J Hyperthermia. 30:6–10. 2014. View Article : Google Scholar : PubMed/NCBI