Local iontophoretic administration of cytotoxic therapies to solid tumors

James D. Byrne, Mohammad R N Jajja, Adrian T. O'Neill, Lissett R. Bickford, Amanda W. Keeler, Nabeel Hyder, Kyle Wagner, Allison Deal, Ryan E. Little, Richard A. Moffitt, Colleen Stack, Meredith Nelson, Christopher R. Brooks, William Lee, J. Chris Luft, Mary E. Napier, David Darr, Carey K. Anders, Richard Stack, Joel E. TepperAndrew Z. Wang, William C. Zamboni, Jen Jen Yeh, Joseph M. DeSimone

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Parenteral and oral routes have been the traditional methods of administering cytotoxic agents to cancer patients. Unfortunately, the maximum potential effect of these cytotoxic agents has been limited because of systemic toxicity and poor tumor perfusion. In an attempt to improve the efficacy of cytotoxic agents while mitigating their side effects, we have developed modalities for the localized iontophoretic delivery of cytotoxic agents. These iontophoretic devices were designed to be implanted proximal to the tumor with external control of power and drug flow. Three distinct orthotopic mouse models of cancer and a canine model were evaluated for device efficacy and toxicity. Orthotopic patient-derived pancreatic cancer xenografts treated biweekly with gemcitabine via the device for 7 weeks experienced a mean log2 fold change in tumor volume of -0.8 compared to a mean log2 fold change in tumor volume of 1.1 for intravenous (IV) gemcitabine, 3.0 for IV saline, and 2.6 for device saline groups. The weekly coadministration of systemic cisplatin therapy and transdermal device cisplatin therapy significantly increased tumor growth inhibition and doubled the survival in two aggressive orthotopic models of breast cancer. The addition of radiotherapy to this treatment further extended survival. Device delivery of gemcitabine in dogs resulted in more than 7-fold difference in local drug concentrations and 25-fold lower systemic drug levels than the IV treatment. Overall, these devices have potential paradigm shifting implications for the treatment of pancreatic, breast, and other solid tumors.

Original languageEnglish
Pages (from-to)273ra14
JournalScience Translational Medicine
Volume7
Issue number273
DOIs
StatePublished - Feb 4 2015
Externally publishedYes

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gemcitabine
Equipment and Supplies
Cytotoxins
Neoplasms
Tumor Burden
Cisplatin
Therapeutics
Survival
Drug and Narcotic Control
Pancreatic Neoplasms
Heterografts
Pharmaceutical Preparations
Canidae
Breast
Radiotherapy
Perfusion
Dogs
Breast Neoplasms
Growth

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Byrne, J. D., Jajja, M. R. N., O'Neill, A. T., Bickford, L. R., Keeler, A. W., Hyder, N., ... DeSimone, J. M. (2015). Local iontophoretic administration of cytotoxic therapies to solid tumors. Science Translational Medicine, 7(273), 273ra14. https://doi.org/10.1126/scitranslmed.3009951

Local iontophoretic administration of cytotoxic therapies to solid tumors. / Byrne, James D.; Jajja, Mohammad R N; O'Neill, Adrian T.; Bickford, Lissett R.; Keeler, Amanda W.; Hyder, Nabeel; Wagner, Kyle; Deal, Allison; Little, Ryan E.; Moffitt, Richard A.; Stack, Colleen; Nelson, Meredith; Brooks, Christopher R.; Lee, William; Luft, J. Chris; Napier, Mary E.; Darr, David; Anders, Carey K.; Stack, Richard; Tepper, Joel E.; Wang, Andrew Z.; Zamboni, William C.; Yeh, Jen Jen; DeSimone, Joseph M.

In: Science Translational Medicine, Vol. 7, No. 273, 04.02.2015, p. 273ra14.

Research output: Contribution to journalArticle

Byrne, JD, Jajja, MRN, O'Neill, AT, Bickford, LR, Keeler, AW, Hyder, N, Wagner, K, Deal, A, Little, RE, Moffitt, RA, Stack, C, Nelson, M, Brooks, CR, Lee, W, Luft, JC, Napier, ME, Darr, D, Anders, CK, Stack, R, Tepper, JE, Wang, AZ, Zamboni, WC, Yeh, JJ & DeSimone, JM 2015, 'Local iontophoretic administration of cytotoxic therapies to solid tumors', Science Translational Medicine, vol. 7, no. 273, pp. 273ra14. https://doi.org/10.1126/scitranslmed.3009951
Byrne JD, Jajja MRN, O'Neill AT, Bickford LR, Keeler AW, Hyder N et al. Local iontophoretic administration of cytotoxic therapies to solid tumors. Science Translational Medicine. 2015 Feb 4;7(273):273ra14. https://doi.org/10.1126/scitranslmed.3009951
Byrne, James D. ; Jajja, Mohammad R N ; O'Neill, Adrian T. ; Bickford, Lissett R. ; Keeler, Amanda W. ; Hyder, Nabeel ; Wagner, Kyle ; Deal, Allison ; Little, Ryan E. ; Moffitt, Richard A. ; Stack, Colleen ; Nelson, Meredith ; Brooks, Christopher R. ; Lee, William ; Luft, J. Chris ; Napier, Mary E. ; Darr, David ; Anders, Carey K. ; Stack, Richard ; Tepper, Joel E. ; Wang, Andrew Z. ; Zamboni, William C. ; Yeh, Jen Jen ; DeSimone, Joseph M. / Local iontophoretic administration of cytotoxic therapies to solid tumors. In: Science Translational Medicine. 2015 ; Vol. 7, No. 273. pp. 273ra14.
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