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Published in: Annals of Surgical Oncology 1/2009

01-01-2009 | Melanomas

Bleomycin-Based Electrochemotherapy: Clinical Outcome from a Single Institution’s Experience with 52 Patients

Authors: Luca G. Campana, Simone Mocellin, Michela Basso, Oliviero Puccetti, Gian Luca De Salvo, Vanna Chiarion-Sileni, Antonella Vecchiato, Luigi Corti, Carlo R. Rossi, Donato Nitti

Published in: Annals of Surgical Oncology | Issue 1/2009

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Abstract

Electrochemotherapy (ECT) has emerged as a complementary treatment for superficial metastases. Fifty-two consecutive patients with different cancer histotypes, mainly melanoma and breast cancer, with disease unsuitable for conventional treatments underwent bleomycin-based ECT for cutaneous and subcutaneous metastases. Toxicity, local response, response duration, and the impact on quality of life were evaluated. A total of 608 tumor nodules were treated (mean, 12 per patient), with 27% of patients affected by nodules >3 cm in size. Treatment was tolerated well, especially under general sedation. An objective response was obtained in 50 (96%) of 52 patients 1 month after the first application. Twenty-two patients underwent a second treatment (because of partial response or the appearance of new lesions). Partial response at first ECT achieved a response consolidation at second application: 80% complete response, 20% partial response. Some patients underwent up to five treatments because of new lesions, but maintained superficial tumor control. After a mean follow-up of 9 (range, 2–21) months, only two patients experienced relapse in the treatment field. Through a nonvalidated eight-item questionnaire (assessing wound healing and bleeding, aesthetic impairment, daily activities, social relations, pain, treatment satisfaction, acceptance of retreatment), most patients reported a benefit in local disease-related complaints and in activity of daily living. In a palliative setting, ECT proved to be safe, effective in all tumors treated, and useful in preserving patients’ quality of life. This benefit, although preliminary, deserves further assessment after a formal validation of the dedicated questionnaire.
Literature
1.
go back to reference Chen C, Smye SW, Robinson MP, et al. Membrane electroporation theories: a review. Med Biol Eng Comput. 2006;44:5–14.CrossRefPubMed Chen C, Smye SW, Robinson MP, et al. Membrane electroporation theories: a review. Med Biol Eng Comput. 2006;44:5–14.CrossRefPubMed
2.
go back to reference Somiari S, Glasspool-Malone J, Drabick JJ, et al. Theory and in vivo application of electroporative gene delivery. Mol Ther. 2000;3:178–87.CrossRef Somiari S, Glasspool-Malone J, Drabick JJ, et al. Theory and in vivo application of electroporative gene delivery. Mol Ther. 2000;3:178–87.CrossRef
3.
go back to reference Heller R, Jaroszeski MJ, Atkin A, et al. In vivo gene electroinjection and expression in rat liver. FEBS Lett. 1996;389:225–8.CrossRefPubMed Heller R, Jaroszeski MJ, Atkin A, et al. In vivo gene electroinjection and expression in rat liver. FEBS Lett. 1996;389:225–8.CrossRefPubMed
4.
go back to reference Cemazar M, Sersa G. Electrotransfer of therapeutic molecules into tissues. Curr Opin Mol Ther. 2007;9:554–62.PubMed Cemazar M, Sersa G. Electrotransfer of therapeutic molecules into tissues. Curr Opin Mol Ther. 2007;9:554–62.PubMed
5.
go back to reference Mossop BJ, Barr RC, Henshaw W, et al. Electric fields in tumors exposed to external voltage sources: implication for electric field-mediated drug and gene delivery. Ann Biochem Eng. 2006;34:1564–72.CrossRef Mossop BJ, Barr RC, Henshaw W, et al. Electric fields in tumors exposed to external voltage sources: implication for electric field-mediated drug and gene delivery. Ann Biochem Eng. 2006;34:1564–72.CrossRef
6.
go back to reference Mir LM. Terapeutic perspectives of in vivo cell electropermeabilization. Bioelecrtochemistry. 2000;53:1–10.CrossRef Mir LM. Terapeutic perspectives of in vivo cell electropermeabilization. Bioelecrtochemistry. 2000;53:1–10.CrossRef
7.
go back to reference Belehradek M, Domenge C, Luboinski B, et al. Electrochemotherapy, a new antitumor treatment. First clinical phase I–II trial. Cancer. 1993;72:3694–700.CrossRefPubMed Belehradek M, Domenge C, Luboinski B, et al. Electrochemotherapy, a new antitumor treatment. First clinical phase I–II trial. Cancer. 1993;72:3694–700.CrossRefPubMed
8.
go back to reference Mir LM, Orlowski S. Mechanisms of electrochemotherapy. Adv Drug Del Rev. 1999;35:107–18.CrossRef Mir LM, Orlowski S. Mechanisms of electrochemotherapy. Adv Drug Del Rev. 1999;35:107–18.CrossRef
9.
go back to reference Gothelf A, Mir LM, Gehl J. Electrochemotherapy: results of cancer treatment using enhanced delivery of bleomycin by electroporation. Cancer Treat Rev. 2003;29:371–87.CrossRefPubMed Gothelf A, Mir LM, Gehl J. Electrochemotherapy: results of cancer treatment using enhanced delivery of bleomycin by electroporation. Cancer Treat Rev. 2003;29:371–87.CrossRefPubMed
10.
go back to reference Serša G. The state-of-the-art of electrochemotherapy before the ESOPE study; advantages and clinical use. EJC Suppl. 2006;4:52–9. Serša G. The state-of-the-art of electrochemotherapy before the ESOPE study; advantages and clinical use. EJC Suppl. 2006;4:52–9.
11.
go back to reference Mir LM, Gehl J, Sersa G, et al. Standard operating procedures of the Electrochemotherapy: instructions for the use of bleomycin or cisplatin administered either systemically or locally and electric pulses delivered by the Cliniporator by means of invasive or non-invasive electrodes. EJC Suppl. 2006;4:14–25.CrossRef Mir LM, Gehl J, Sersa G, et al. Standard operating procedures of the Electrochemotherapy: instructions for the use of bleomycin or cisplatin administered either systemically or locally and electric pulses delivered by the Cliniporator by means of invasive or non-invasive electrodes. EJC Suppl. 2006;4:14–25.CrossRef
12.
go back to reference Marty M, Serša G, Garbay JR, et al. Electrochemotherapy—An easy, highly effective and safe treatment of cutaneous and subcutaneous metastases: results of ESOPE study. EJC Suppl. 2006;4:3–13.CrossRef Marty M, Serša G, Garbay JR, et al. Electrochemotherapy—An easy, highly effective and safe treatment of cutaneous and subcutaneous metastases: results of ESOPE study. EJC Suppl. 2006;4:3–13.CrossRef
13.
go back to reference Berle I. Clinical photography and patient rights: the need for orthopraxy. J Med Ethics. 2008;34:89–92.CrossRefPubMed Berle I. Clinical photography and patient rights: the need for orthopraxy. J Med Ethics. 2008;34:89–92.CrossRefPubMed
14.
go back to reference Therasse P, Arbuck SG, Eisenhauer EA. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–16.CrossRefPubMed Therasse P, Arbuck SG, Eisenhauer EA. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–16.CrossRefPubMed
16.
go back to reference Rols MP, Bachaud JM, Giraud P, et al. Electrochemotherapy of cutaneous metastases in malignant melanoma. Melanoma Res. 2000;10:468–74.CrossRefPubMed Rols MP, Bachaud JM, Giraud P, et al. Electrochemotherapy of cutaneous metastases in malignant melanoma. Melanoma Res. 2000;10:468–74.CrossRefPubMed
17.
go back to reference Giardino R, Fini M, Bonazzi V, et al. Electrochemotherapy a novel approach to the treatment of metastatic nodules on the skin and subcutaneous tissues. Biomed Pharmacol. 2006;60:458–62.CrossRef Giardino R, Fini M, Bonazzi V, et al. Electrochemotherapy a novel approach to the treatment of metastatic nodules on the skin and subcutaneous tissues. Biomed Pharmacol. 2006;60:458–62.CrossRef
18.
go back to reference Garbay JR, Billard V, Bernat C, et al. Successful repetitive treatments by Electrochemotherapy of multiple unresectable Kaposi sarcoma nodules. EJC Suppl. 2006;4:29–31.CrossRef Garbay JR, Billard V, Bernat C, et al. Successful repetitive treatments by Electrochemotherapy of multiple unresectable Kaposi sarcoma nodules. EJC Suppl. 2006;4:29–31.CrossRef
19.
go back to reference Whelan MC, Larkin JO, Collins CG, et al. Effective treatment of an extensive recurrent breast cancer which was refractory to multimodal therapy by multiple applications of Electrochemotherapy. EJC Suppl. 2006;4:32–4.CrossRef Whelan MC, Larkin JO, Collins CG, et al. Effective treatment of an extensive recurrent breast cancer which was refractory to multimodal therapy by multiple applications of Electrochemotherapy. EJC Suppl. 2006;4:32–4.CrossRef
20.
go back to reference Colombo GL, Di Matteo S, Mir LM. Cost-effectiveness of Electrochemotherapy with the Cliniporator vs other methods for the control and treatment of cutaneous and subcutaneous tumors. Ther Clin Risk Manag. 2008;4:1–8. Colombo GL, Di Matteo S, Mir LM. Cost-effectiveness of Electrochemotherapy with the Cliniporator vs other methods for the control and treatment of cutaneous and subcutaneous tumors. Ther Clin Risk Manag. 2008;4:1–8.
21.
go back to reference Mir LM, Glass LF, Sersa G, et al. Effective treatment of cutaneous and subcutaneous malignant tumours by electrochemotherapy. Br J Cancer. 1998;77:2336–42.CrossRefPubMedPubMedCentral Mir LM, Glass LF, Sersa G, et al. Effective treatment of cutaneous and subcutaneous malignant tumours by electrochemotherapy. Br J Cancer. 1998;77:2336–42.CrossRefPubMedPubMedCentral
22.
go back to reference Byrne MC, Thompson JF, Johnston H, et al. Treatment of metastatic melanoma using electroporation therapy with bleomycin (electrochemotherapy). Melanoma Res. 2005;15:45–51.CrossRefPubMed Byrne MC, Thompson JF, Johnston H, et al. Treatment of metastatic melanoma using electroporation therapy with bleomycin (electrochemotherapy). Melanoma Res. 2005;15:45–51.CrossRefPubMed
23.
go back to reference Gaudy C, Richard MA, Folchetti G, et al. Randomized controlled study of Electrochemotherapy in the local treatment of skin metastases of melanoma. J Cutan Med Surg. 2006, 10:115–21.CrossRefPubMed Gaudy C, Richard MA, Folchetti G, et al. Randomized controlled study of Electrochemotherapy in the local treatment of skin metastases of melanoma. J Cutan Med Surg. 2006, 10:115–21.CrossRefPubMed
24.
go back to reference Larkin JO, Collins CG, Aarons S, et al. Electrochemotherapy: aspects of preclinical development and early clinical experience. Ann Surg. 2007;245:469–79.CrossRefPubMedPubMedCentral Larkin JO, Collins CG, Aarons S, et al. Electrochemotherapy: aspects of preclinical development and early clinical experience. Ann Surg. 2007;245:469–79.CrossRefPubMedPubMedCentral
25.
go back to reference Quaglino P, Mortera C, Osella-Abate S, et al. Electrochemotherapy with intravenous bleomycin in the local treatment of skin melanoma metastases. Ann Surg Oncol. 2008;15:2215–22.CrossRefPubMed Quaglino P, Mortera C, Osella-Abate S, et al. Electrochemotherapy with intravenous bleomycin in the local treatment of skin melanoma metastases. Ann Surg Oncol. 2008;15:2215–22.CrossRefPubMed
26.
go back to reference Domenge C, Orlowski S, Luboinski B, et al. Antitumor electrochemotherapy: new advances in the clinical protocol. Cancer. 1996;77:956–63.CrossRefPubMed Domenge C, Orlowski S, Luboinski B, et al. Antitumor electrochemotherapy: new advances in the clinical protocol. Cancer. 1996;77:956–63.CrossRefPubMed
27.
go back to reference Gilbert RA, Jaroszeski MJ, Heller R. Novel electrode designs for electrochemotherapy. Biochim Biophys Acta. 1997;1334:9–14.CrossRefPubMed Gilbert RA, Jaroszeski MJ, Heller R. Novel electrode designs for electrochemotherapy. Biochim Biophys Acta. 1997;1334:9–14.CrossRefPubMed
28.
go back to reference Heller L, Pottinger C, Jaroszeski MJ, et al. In vivo electroporation of plasmids encoding GM-CSF or interleukin-2 into existing B16 melanomas combined with electrochemotherapy induces long-term antitumour immunità. Melanoma Res. 2000;10:577–83.CrossRefPubMed Heller L, Pottinger C, Jaroszeski MJ, et al. In vivo electroporation of plasmids encoding GM-CSF or interleukin-2 into existing B16 melanomas combined with electrochemotherapy induces long-term antitumour immunità. Melanoma Res. 2000;10:577–83.CrossRefPubMed
29.
go back to reference Roux S, Bernat C, Al-Sakere B, et al. Tumor destruction using electrochemotherapy followed by CpG oligodeoxynucleotide injection induces distant tumor responses. Cancer Immunol Immunother. 2008;57:1291–300.CrossRefPubMed Roux S, Bernat C, Al-Sakere B, et al. Tumor destruction using electrochemotherapy followed by CpG oligodeoxynucleotide injection induces distant tumor responses. Cancer Immunol Immunother. 2008;57:1291–300.CrossRefPubMed
30.
go back to reference Serša G, Kranjc S, Čemažar M, et al. Improvement of combined modality therapy with cisplatin and radiation using electroporation of tumors. Int J Radiat Oncol Biol Phys. 2000;46:1037–41.CrossRefPubMed Serša G, Kranjc S, Čemažar M, et al. Improvement of combined modality therapy with cisplatin and radiation using electroporation of tumors. Int J Radiat Oncol Biol Phys. 2000;46:1037–41.CrossRefPubMed
31.
go back to reference Serša G, Štabuc B, Čemažar M, et al. Electrochemotherapy with cisplatin: the systemic antitumor effectiveness of cisplatin can be potentiated locally by the application of electric pulses in the treatment of malignant melanoma skin metastases. Melanoma Res. 2000, 10:381–5.CrossRefPubMed Serša G, Štabuc B, Čemažar M, et al. Electrochemotherapy with cisplatin: the systemic antitumor effectiveness of cisplatin can be potentiated locally by the application of electric pulses in the treatment of malignant melanoma skin metastases. Melanoma Res. 2000, 10:381–5.CrossRefPubMed
32.
go back to reference Zitvogel L, Apetoh L, Ghiringhelli F, et al. Immunological aspects of cancer chemotherapy. Nat Rev Immunol. 2008;8:59–73.CrossRefPubMed Zitvogel L, Apetoh L, Ghiringhelli F, et al. Immunological aspects of cancer chemotherapy. Nat Rev Immunol. 2008;8:59–73.CrossRefPubMed
33.
go back to reference Wagner LI, Wenzel L, Shaw E, et al. Patient-reported outcomes in Phase II cancer clinical trials: lesson learned and future directions. J Clin Oncol. 2007;25:5058–62.CrossRefPubMed Wagner LI, Wenzel L, Shaw E, et al. Patient-reported outcomes in Phase II cancer clinical trials: lesson learned and future directions. J Clin Oncol. 2007;25:5058–62.CrossRefPubMed
Metadata
Title
Bleomycin-Based Electrochemotherapy: Clinical Outcome from a Single Institution’s Experience with 52 Patients
Authors
Luca G. Campana
Simone Mocellin
Michela Basso
Oliviero Puccetti
Gian Luca De Salvo
Vanna Chiarion-Sileni
Antonella Vecchiato
Luigi Corti
Carlo R. Rossi
Donato Nitti
Publication date
01-01-2009
Publisher
Springer New York
Published in
Annals of Surgical Oncology / Issue 1/2009
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-008-0204-8

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