Skip to main content
SpringerLink
Log in

Clinical Trials for Solid Tumors Using Electrochemotherapy

  • Protocol
Electrochemotherapy, Electrogenetherapy, and Transdermal Drug Delivery

Part of the book series: Methods in Molecular Medicine ((MIMM,volume 37))

Abstract

Chemotherapy is a standard treatment for a wide variety of cancers. However, response rates are usually low. In melanoma, for example, partial response rates range from 20–45 % with complete responses of less than 5% (1–4). The cell membrane can be a significant barrier for agents with an intracellular site of action. The inability to cross the cell membrane and enter the cell could lead to a low response rate. The effectiveness of these agents could be enhanced if combined with a procedure that increases the permeability of the cell membrane.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Coates, A. S. (1992) Systemic chemotherapy for malignant melanoma. World J.Surg. 16, 277–281.

    Article  PubMed  CAS  Google Scholar 

  2. Nathanson, L. and Jilani, S. (1993) Chemotherapy of malignant melanoma. Cancer Treat. Rev. 19, 17–28.

    Article  Google Scholar 

  3. Yeung, R. S. (1994) Management of recurrent cutaneous melanoma. Curr. Probl. Cancer 18, 143–186.

    Article  PubMed  CAS  Google Scholar 

  4. Buzaid, A. C. and Murren, J. (1992) Chemotherapy for advanced malignant melanoma. Int. J. Clin. Lab. Res. 21, 205–209.

    Article  PubMed  CAS  Google Scholar 

  5. Chang, D. C., Chassy, B. M., Saunders, J. A., and Sowers, A. E. (1992) Guide to Electroporation and Electrofusion. Academic Press. San Diego, CA.

    Google Scholar 

  6. Potter, H. (1988) Electroporation in biology: Methods, applications and instrumentation. Anal. Biochem. 174, 361–373.

    Article  PubMed  CAS  Google Scholar 

  7. Weaver, J. C. (1993) Electroporation: a general phenomenon for manipulating cells and tissues. J. Cell. Biochem. 51, 426–435.

    PubMed  CAS  Google Scholar 

  8. Heller, R. and Gilbert, R. (1992) Biological applications of cell-tissue electrofusion. Guide to Electroporation and Electrofusion (Chang, D. C., Chassy, B. M., Saunders, J. A., and Sowers, A. E., eds.). Academic Press, San Diego, CA, pp. 393–410

    Google Scholar 

  9. Foung, S. K. H. and Perkins, S. (1989) Electric field-induced cell fusion and human monoclonal antibodies. J. Immunol. Methods 116, 117–122.

    Article  PubMed  CAS  Google Scholar 

  10. Lo, M. M. S., Tsong, T. Y., Conrad, M. K., Strittmatter, S. M., Hester, L. D., and Snyder, S. H. (1984) Monoclonal antibody production by receptor-mediated electrically induced cell fusion. Nature 310, 792–794.

    Article  PubMed  CAS  Google Scholar 

  11. Teissié, J., Knutson, V. P., Tsong, T. Y., and Lane, M. D. (1982) Electric pulseinduced fusion of 3T3 cells in monolayer culture. Science 216, 537–538.

    Article  PubMed  Google Scholar 

  12. Jaroszeski, M. J., Gilbert, R., Fallon, P. G., and Heller, R. (1994) Mechanically facilitated cell-cell electrofusion. Biophys. J. 67, 1574–1581.

    Article  PubMed  CAS  Google Scholar 

  13. Heller, R. and Grasso, R. J. (1990) Transfer of human membrane surface components by incorporating human cells into intact animal tissue by cell-tissue electrofusion in vivo. Biochem. Biophys. Acta 1024, 185–188.

    Article  PubMed  CAS  Google Scholar 

  14. Grasso, R. J., Heller, R., Cooley, J. C., and Haller, E. M. (1989) Electrofusion of individual animal cells directly to intact corneal epithelial tissue. Biochem. Biophys. Acta 980, 9–14.

    Article  PubMed  CAS  Google Scholar 

  15. Mouneimne, Y., Pierre-Francois, T. Barhoumi, R., and Nicolau, C. (1991) Electroinsertion of xeno proteins in red blood cell membranes yields a long lived protein carrier in circulation. Biochim. Biophys. Acta 1066, 83–89.

    Article  PubMed  CAS  Google Scholar 

  16. Mouneimne, Y., Pierre-Francois, T. Barhoumi, R., and Nicolau, C. (1990) Electroinsertion of full length recombinant CD4 into red blood cell membrane. Biochim. Biophys. Acta 1027, 53–58.

    Article  PubMed  CAS  Google Scholar 

  17. Chernomordik, L. V., Sokolov, A. V., and Budker, V. G. (1990) Electrostimulated uptake of DNA by liposomes. Biochem. Biophys. Acta 1024, 179–183.

    Article  PubMed  CAS  Google Scholar 

  18. Zheng, Q. and Chang, D. C. (1991) High-efficiency gene transfection by in situ electroporation of cultured cells. Biochem. Biophys. Acta 1088, 104–110.

    PubMed  CAS  Google Scholar 

  19. Heller, R., Jaroszeski, M. J., Atkin, A., Moradpour, D., Gilbert, R., Wands, J., and Nicolau, C. (1996) In vivo gene electroinjection and expression in rat liver. FEBS Lett. 389, 225–228.

    Article  PubMed  CAS  Google Scholar 

  20. Mir, L. M., Orlowski, S., Belehradek J. Jr., and Paoletti, C. (1991) Electrochemotherapy: Potentiation of antitumor effect of bleomycin by local electric pulses. Eur. J. Cancer 27, 68–72.

    Article  PubMed  CAS  Google Scholar 

  21. Belehradek, J. Jr., Orlowski, S., Poddevin, B., Paoletti, C., and Mir, L. M. (1991) Electrochemotherapy of spontaneous mammory tumors in mice. Eur. J. Cancer 27, 73–76.

    Article  PubMed  Google Scholar 

  22. Jaroszeski, M. J., Gilbert, R., and Heller, R. (1997) Electrochemotherapy: an emerging drug delivery method for the treatment of cancer. Adv. Drug Deliv. Rev. 26, 185–197.

    Article  PubMed  CAS  Google Scholar 

  23. Mir, L. M., Belehradek, M., Domenge, C., Orlowski, S., Poddevin B., Belehradek J. Jr., Schwab, G., Luboinski, B., and Paoletti, C. (1991) Electrochemotherapy, a novel antitumor treatment: First clinical trial. C. R. Acad. Sci. Paris 313, 613–618.

    PubMed  CAS  Google Scholar 

  24. Belehradek, M., Domenge, C., Luboinnski, B., Orlowski, S., Belehradek, J., and Mir, L. M. (1993) Electrochemotherapy, a new antitumor treatment: First clinical phase I-II trial. Cancer 72, 3694–3700.

    Article  PubMed  CAS  Google Scholar 

  25. Domenge, C., Orlowski, S., Luboinski, B., De Baere, T., Schwaab, G., Belehradek J. Jr., and Mir, L. M. (1996) Antitumor electrochemotherapy: New advances in the clinical protocol. Cancer 77, 956–963.

    Article  PubMed  CAS  Google Scholar 

  26. Heller, R., Jaroszeski, M. J., Glass, L. F., Messina, J. L., Rapaport, D. P., DeConti, R. C., Fenske, N. A., Gilbert, R., Mir, L. M., and Reintgen, D. S. (1996) Phase I/ II trial for the treatment of cutaneous and subcutaneous tumors using electrochemotherapy. Cancer 77, 964–971.

    Article  PubMed  CAS  Google Scholar 

  27. Reintgen, D. S., Jaroszeski, M. J., and Heller, R. (1996) Electrochemotherapy: A novel approach to cancer. J. Skin Cancer Foundation 14, 17–19, 83.

    Google Scholar 

  28. Glass, L. F., Pepine, M. L., Fenske, N. A., Jaroszeski, M. J., Reintgen, D. S., and Heller, R. (1996) Bleomycin-mediated electrochemotherapy of metastatic melanoma. Arch. Dermatol. 132, 1353–1357.

    Article  PubMed  CAS  Google Scholar 

  29. Rudolf, Z., Štabuc, B., Čemažar, M., Miklavčič, D., Vodovnik, L., and Serša, G. (1995) Electrochemotherapy with bleomycin: The first clinical experience in malignant melanoma patients. Radiol. Oncol. 29, 229–235.

    Google Scholar 

  30. Mir, L. M., Glass, L. F., Serša, G., Teissié, J., Domenge, C., Miklavčič, D., Jaroszeski, M. J., Orlowski, S., Reintgen, D. S., Rudolf, Z., Belehradek, M., Gilbert, R., Rols, M-P, Belehradek, J. Jr., Bachaud. J. M., De Conti, R. C., Štabuc, B., Čemažar, M., Coninx, P., and Heller, R. (1998) Effective treatment of cutaneous and subcutaneous malignant tumours by electrochemotherapy. Br. J. Cancer 77, 2336–2342.

    Article  PubMed  CAS  Google Scholar 

  31. Glass, L. F., Jaroszeski, M. J., Gilbert, R., Reintgen, D. S., and Heller, R. (1997) Intralesional bleomycin-mediated electrochemotherapy in 20 patients with basal cell carcinoma. J. Am. Acad. Dermatol. 37, 596–599.

    Article  PubMed  CAS  Google Scholar 

  32. Heller, R., Jaroszeski, M. J., Reintgen, D., Puleo, C., DeConti, R., Gilbert, R., and Glass, L. F. (1998) Treatment of cutaneous and subcutaneous tumors with electrochemotherapy using intralesional bleomycin. Cancer 83, 148–157.

    Article  PubMed  CAS  Google Scholar 

  33. Panje, W. R., Hier, M. P., Garman, G. R., Harrell, E., Goldman, A., and Bloch, I. (1998) Electroporation therapy of head and neck cancer. Ann. Otol. Rhinol. Laryngol. 107, 779–785.

    PubMed  CAS  Google Scholar 

  34. Hofmann, G. A., Dev, S. B., and Nanda, G. S. (1996) Electrochemotherapy: transition from laboratory to the clinic. IEEE Eng. Med. Biol. 15, 124–132.

    Article  Google Scholar 

  35. Gilbert, R., Jaroszeski, M. J., and Heller, R. (1997) Novel electrode designs for electrochemotherapy. Biochem. Biophys. Acta 1334, 9–14.

    PubMed  CAS  Google Scholar 

  36. Serša, G., Štabuc, B., Čemažar, M., Jančar, B., Miklavčič, D., and Rudolf, Z. (1998) Electrochemotherapy with cisplatin: Potentiation of local cisplatin antitumor effectiveness by application of electric pulses in cancer patients. Eur. J. Cancer 34, 1213–1218.

    Article  PubMed  Google Scholar 

  37. Serša, G., Čemažar, M., Semrov, D., and Miklavčič, D. (1996) Changing electrode orientation improves the efficacy of electrochemotherapy of solid tumors in mice. Bioelectrochem. Bioenerg. 39, 61–66.

    Article  Google Scholar 

  38. Čemažar, M., Miklavčič, D., Vodovnik, L., Jarm, T., Zvonimir, R., Štabuc, B., Čufer, T., and Serša, G. (1995) Improved therapeutic effect of electrochemo therapy with cisplatin by intratumoral drug administration and changing of electrode orientation for electropermeabilization on EAT tumor model in mice. Radiol. Oncol. 29, 121–127.

    Google Scholar 

  39. Okino, M., Tomie, H., Kanesada, H., Marumoto, M., Esato, K., and Suzuki, H. (1992) Optimal electric conditions in electrical impulse chemotherapy. Jpn. J. Cancer Res. 83, 1095–1101.

    PubMed  CAS  Google Scholar 

  40. Heller, R., Jaroszeski, M., Messina, J. L., Perrott, R., Van Voorhis, N., Reintgen, D. D., and Gilbert, R. (1995) Treatment of B16 melanoma with the combination of electroporation and chemotherapy. Bioelectrochem. Bioenerg. 36, 83–87.

    Article  CAS  Google Scholar 

  41. Sersa, G., Cemazar, M., Miklavcic, D., and Mir, L. M. (1994) Electrochemotherapy: variable anti-tumor effect on different tumor models. Bioelectrochem. Bioenerg. 35, 23–27.

    Article  CAS  Google Scholar 

  42. Heller, R., Jaroszeski, M. J., Perrott, R., Messina, J., and Gilbert, R. (1997) Effective treatment of B16 melanoma by direct delivery of bleomycin using electrochemotherapy. Melanoma Res. 7, 10–18.

    Article  PubMed  CAS  Google Scholar 

  43. Okino, M., Marumoto, M., Kanesada, H., Kuga, K., and Mohri, H. (1987) Electrical impulse chemotherapy for rat solid tumors. Proc. Jpn. Cancer Congr. 46, 420.

    Google Scholar 

  44. Okino, M. and Esato, K. (1990) The effects of a single high voltage electrical stimulation with anticancer drug on in vivo growing malignant tumors. Jpn. J. Surg. 20, 197–204.

    Article  PubMed  CAS  Google Scholar 

  45. Okino, M., Tomie, H., Kanesada, H., Marumoto, M., Morita, N., Esato, K., and Suzuki, H. (1991) Induction of tumor specific selective toxicity in electrical impulse chemotherapy-analysis of dose response curve. Oncologia 24, 71–79.

    Google Scholar 

  46. Kanesada, H. (1990) Anticancer effect of high voltage pulses combined with concentration dependent anticancer drugs on Lewis lung carcinoma. J. Jpn. Soc. Cancer Ther. 25, 2640–2648.

    CAS  Google Scholar 

  47. Salford, L. G., Persson, B. R. R., Brun, A., Ceberg, C. P., Kongstad, P. Ch., and Mir, L. M. (1993) A new brain tumor therapy combining bleomycin with in vivo electropermeabilization. Biochem. Biophys. Res. Commun. 194, 938–943.

    Article  PubMed  CAS  Google Scholar 

  48. Yamaguchi, O., Irisawa, C., Baba, K., Ogihara, M., Yokota, T., and Shiraiwa, Y. (1994) Potentiation of antitumor effect of bleomycin by local electric pulses in mouse bladder tumor. Tohoku J. Exp. Med. 172, 291–293.

    Article  PubMed  CAS  Google Scholar 

  49. Jaroszeski, M. J., Gilbert, R., and Heller, R. (1997) Successful treatment of hepatomas with electrochemotherapy in a rat model. Biochem. Biophys. Acta 1334, 15–18.

    PubMed  CAS  Google Scholar 

  50. Jaroszeski, M. J., Gilbert, R., Perrott, R., and Heller, R. (1996) Enhanced effects of multiple treatment electrochemotherapy. Melanoma Res. 6, 427–433.

    Article  PubMed  CAS  Google Scholar 

  51. Mir, L. M., Devauchelle, P., Quintin-Colonna, F., Delisle, F., Fradelizi, D., Belehradek, J. Jr., and Orlowski, S. (1997) First clinical trial of cat soft-tissue sarcomas treatment by electrochemotherapy. Br. J. Cancer 76, 1617–1622.

    Article  PubMed  CAS  Google Scholar 

  52. Balch, C. M., Houghton, A. N., and Peters, L. J. (1993) Cancer Principles and Practice of Oncology. (DeVita Jr., V. T., Hellman, S., and Rosenberg, S. A., eds.) Lippincott, Philadelphia, p. 1637 and Table 46-7.

    Google Scholar 

  53. Retsas, S. (1995) Strategies for improving survival in malignant melanoma; focus on vindesine. J. Drug Dev. Clin. Prac. 7, 159–171.

    CAS  Google Scholar 

  54. Pron, G., Belehradek, J. Jr. and Mir, L. M. (1993) Identification of a plasma membrane protein that specifically binds bleomycin. Biochem. Biophys. Res. Commun. 194, 333–337.

    Article  PubMed  CAS  Google Scholar 

  55. Poddevin, B., Orlowski, S., Belehradek, J. Jr., and Mir, L. M. (1991) Very high cytotoxicity of bleomycin introduced into the cytosol of cells in culture. Biochem. Pharmacol. 42 (Suppl.), 67–75.

    Article  Google Scholar 

  56. Neumann, E., Sowers, A. E., and Jordan, C. A. (1989) Electroporation and Electrofusion in Cell Biology. Plenum, New York.

    Google Scholar 

  57. Orlowski, S. and Mir, L. M. (1993) Cell electropermeabilization: A new tool for biochemical and pharmacological studies. Biochim. Biophys. Acta 1154, 51–63.

    PubMed  CAS  Google Scholar 

  58. Tounekti, O., Pron, G., Belehradek, J. Jr., and Mir, L. M. (1993) Bleomycin, an apoptosis-mimetic drug that induces two types of cell death depending on the number of molecules internalized. Cancer Res. 53, 5462-5469.

    Google Scholar 

  59. Reed, E. (1993) Platinum analogs. In: Cancer Principles and Practice of Oncology. (DeVita, V. T. Jr, Hellman, S., and Rosenberg, S. A., eds.). Lippincott, Philadelphia, pp. 390–400.

    Google Scholar 

  60. Mir, L. M., Orlowski, S., Poddevin, B., and Belehradek, J. Jr. (1992) Electrochemotherapy tumor treatment is improved by interleukin-2 stimulation of the host’s defenses. Eur. Cytokine Netw. 3, 331–334.

    PubMed  CAS  Google Scholar 

  61. Mir, L. M., Roth, C., Orlowski, S., Belehradek, J. Jr., Fradelizi, F., Paoletti, C., and Kourilsky, P. (1992) Potentiation of the antitumoral effect of electrochemotherapy by an immunotherapy with allogeneic cells producing interleukin-2. C. R. Acad. Sci. Paris 314, 539–544.

    PubMed  CAS  Google Scholar 

  62. Mir, L. M., Roth, C., Orlowski, S., Quintin-Colonna, F., Fradelizi, F., Belehradek, J. Jr., and Kourilsky, P. (1995) Systemic antitumor effects of electrochemotherapy combined with histocompatible cells secreting interleukin-2. J. Immunol. 17, 30–38.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, College of Medicine, University of South Florida, Tampa, FL

    Richard Heller & Mark J. Jaroszeski

  2. Department of Chemical Engineering, College of Engineering, University of South Florida, Tampa, FL

    Richard Gilbert

Authors
  1. Richard Heller
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richard Gilbert
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mark J. Jaroszeski
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of South Florida College of Medicine, USA

    Mark J. Jaroszeski PhD  & Richard Heller PhD  & 

  2. University of South Florida College of Engineering, USA

    Richard Gilbert PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Humana Press Inc., Totowa, NJ

About this protocol

Cite this protocol

Heller, R., Gilbert, R., Jaroszeski, M.J. (2000). Clinical Trials for Solid Tumors Using Electrochemotherapy. In: Jaroszeski, M.J., Heller, R., Gilbert, R. (eds) Electrochemotherapy, Electrogenetherapy, and Transdermal Drug Delivery. Methods in Molecular Medicine, vol 37. Humana Press. https://doi.org/10.1385/1-59259-080-2:137

Download citation

  • DOI: https://doi.org/10.1385/1-59259-080-2:137

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-606-2

  • Online ISBN: 978-1-59259-080-3

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation