Abstract
Radiotherapy is the use of ionizing radiation in the treatment of malignant tumors. It is one of the main treatment modalities for many forms of cancer, with more than half of all cancer patients receiving radiation therapy at some point in their treatment. Despite the technical progress in targeting ability of radiotherapy, poor therapeutic window remains a problem; therefore in clinical practice radiotherapy is commonly combined with chemotherapy. By using electrochemotherapy, the uptake of the non or poorly permeable chemotherapeutic drugs, bleomycin and cisplatin, into the tumors can be increased and thus also their radiosensitizing effect. In combined treatment of electrochemotherapy preceding irradiation, an increased radio-response was demonstrated with an enhancement factor of up to 4.6, regardless of using radiomimetic (bleomycin) or radiosensitizing (cisplatin) drug. The improved antitumor effectiveness is mainly enabled by increased drug accumulation in the tumors. Radiosensitization was demonstrated in vitro and in vivo in variable tumor models irradiated in a single dose and a fractionated regime. Low and acceptable radiation damage of normal tissue in the irradiation field was observed. All the data provided a starting point for translation of combined electrochemotherapy and tumor irradiation into the clinic, which has already begun.
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References
Begg AC, Deurloo MJ, Kop W, Bartelink H (1994) Improvement of combined modality therapy with cisplatin and radiation using intratumoral drug administration in murine tumors. Radiother Oncol 31(2):129–137
Begg AC, Stewart FA, Vens C (2011) Strategies to improve radiotherapy with targeted drugs. Nat Rev Cancer 11(4):239–253. doi:10.1038/nrc3007
Dorr RT (1992) Bleomycin pharmacology: mechanism of action and resistance, and clinical pharmacokinetics. Semin Oncol 19(2 Suppl 5):3–8
Gorodetsky R, Levy-Agababa F, Mou X, Vexler AM (1998) Combination of cisplatin and radiation in cell culture: effect of duration of exposure to drug and timing of irradiation. Int J Cancer 75(4):635–642
Jiang GL, Ang KK, Thames HD, Wong CS, Wendt CD (1989) Response of plateau-phase C3H 10T1/2 cells to radiation and concurrent administration of bleomycin. Radiat Res 120(2):306–312
Joiner M, van der Kogel A (2009) Basic clinical radiobiology, 4th edn. Taylor & Francis Group, Boca Raton, pp 1–361
Kamrava M, Bernstein MB, Camphausen K, Hodge JW (2009) Combining radiation, immunotherapy, and antiangiogenesis agents in the management of cancer: the three musketeers or just another quixotic combination? Mol Biosyst 5(11):1262–1270
Kranjc S, Cemazar M, Grosel A, Pipan Z, Sersa G (2003a) Effect of electroporation on radiosensitization with cisplatin in two cell lines with different chemo- and radiosensitivity. Radiol Oncol 37:101–107
Kranjc S, Cemazar M, Grosel A, Scancar J, Sersa G (2003b) Electroporation of LPB sarcoma cells in vitro and tumors in vivo increases the radiosensitizing effect of cisplatin. Anticancer Res 23(1A):275–281
Kranjc S, Cemazar M, Grosel A, Sentjurc M, Sersa G (2005) Radiosensitizing effect of electrochemotherapy with bleomycin in LPB sarcoma cells and tumors in mice. BMC Cancer 5:115
Kranjc S, Tevz G, Kamensek U, Vidic S, Cemazar M, Sersa G (2009) Radiosensitizing effect of electrochemotherapy in a fractionated radiation regime in radiosensitive murine sarcoma and radioresistant adenocarcinoma tumor model. Radiat Res 172(6):677–685
Kyrgias G, Kostopoulou E, Zafiriou E, Zygogianni A, Skarlatos J, Roussaki-Schulze AV, Theodorou K (2013) Hidradenocarcinoma of the temporal area successfully treated with concomitant electrochemotherapy and radiotherapy. Head Neck Oncol 5(2):14
Lagrange JL, Fischel JL, Galliani S, Formento P, Guillot T, Bardon M, Milano G (1993) Importance of the irradiation timing within a chemoradiotherapy sequence including cisplatin and 5-FU-folinic acid. Experimental results. Eur J Cancer 29A(11):1531–1535
Mali B, Jarm T, Snoj M, Sersa G, Miklavcic D (2013) Antitumor effectiveness of electrochemotherapy: a systematic review and meta-analysis. Eur J Surg Oncol 39(1):4–16
Mir LM, Orlowski S, Belehradek J Jr, Paoletti C (1991) Electrochemotherapy potentiation of antitumour effect of bleomycin by local electric pulses. Eur J Cancer 27(1):68–72
Raeisi E, Aghamiri SM, Bandi A, Rahmatpour N, Firoozabadi SM, Kafi-Abad SA, Mir LM (2012) The antitumor efficiency of combined electrochemotherapy and single dose irradiation on a breast cancer tumor model. Radiol Oncol 46(3):226–232
Rantanen V, Grénman S, Kulmala J, Grénman R (1995) Simultaneous cisplatin and radiation in endometrial adenocarcinoma cell lines. Acta Oncol 34(1):93–98
Seiwert TY, Salama JK, Vokes EE (2007) The concurrent chemoradiation paradigm-general principles. Nat Clin Pract Oncol 4(2):86–100
Sersa G, Cemazar M, Rudolf Z, Fras P (1999) Adenocarcinoma skin metastases treated by electrochemotherapy with cisplatin combined with radiation. Radiol Oncol 33:291–296
Sersa G, Kranjc S, Cemazar M (2000) Improvement of combined modality therapy with cisplatin and radiation using electroporation of tumors. Int J Radiat Oncol Biol Phys 46(4):1037–1041
Shil P, Sanghvi SH, Vidyasagar PB, Mishra KP (2005) Enhancement of radiation cytotoxicity in murine cancer cells by electroporation: in vitro and in vivo studies. J Environ Pathol Toxicol Oncol 24(4):291–298
Shil P, Kumar A, Vidyasagar PB, Mishra KP (2006) Electroporation enhances radiation and doxorubicin-induced toxicity in solid tumor in vivo. J Environ Pathol Toxicol Oncol 25(4):625–632
Skarlatos I, Kyrgias G, Mosa E, Provatopoulou X, Spyrou M, Theodorou K, Lepouras A, Gounaris A, Koukourakis M (2011) Electrochemotherapy in cancer patients: first clinical trial in Greece. Vivo 25(2):265–274
Spugnini EP1, Dotsinsky I, Mudrov N, Citro G, Caruso G, Cardelli P, Baldi A (2008) Electrochemotherapy-induced radiation recall in a cat. Vivo 22(6):751–753
Strojan P, Vermorken JB, Beitler JJ, Saba NF, Haigentz M Jr, Bossi P, Worden FP, Langendijk JA, Eisbruch A, Mendenhall WM, Lee AW, Harrison LB, Bradford CR, Smee R, Silver CE, Rinaldo A, Ferlito A (2016) Cumulative cisplatin dose in concurrent chemoradiotherapy for head and neck cancer: A systematic review. Head Neck Suppl 1:E2151–E2158
Tiwari G, Tiwari R, Sriwastawa B, Bhati L, Pandey S, Pandey P, Bannerjee SK (2012) Drug delivery systems: An updated review. Int J Pharm Investig 2(1):2–11
West CML (1992) A potential pitfall in the use of electroporation – cellular radiosensitization by pulsed high-voltage electric-fields. Int J Radiat Biol 61(3):329–334
Yarmush ML, Golberg A, Sersa G, Kotnik T, Miklavcic D (2014) Electroporation-based technologies for medicine: principles, applications, and challenges. Annu Rev Biomed Eng 16:295–320
Zakotnik B, Budihna M, Smid L, Soba E, Strojan P, Fajdiga I, Zargi M, Oblak I, Lesnicar H (2007) Patterns of failure in patients with locally advanced head and neck cancer treated postoperatively with irradiation or concomitant irradiation with Mitomycin C and Bleomycin. Int J Radiat Oncol Biol Phys 67(3):685–690
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Kranjc, S., Kamensek, U., Cemazar, M., Sersa, G. (2016). Combined Treatment of Electrochemotherapy with Irradiation. In: Miklavcic, D. (eds) Handbook of Electroporation. Springer, Cham. https://doi.org/10.1007/978-3-319-26779-1_61-1
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DOI: https://doi.org/10.1007/978-3-319-26779-1_61-1
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