Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Dec 30;13(1):39.
doi: 10.3390/pharmaceutics13010039.

Convection Enhanced Delivery of Topotecan for Gliomas: A Single-Center Experience

Pavan S Upadhyayula  1 , Eleonora F Spinazzi  1 , Michael G Argenziano  1 , Peter Canoll  2 , Jeffrey N Bruce  1
Affiliations
Review

Convection Enhanced Delivery of Topotecan for Gliomas: A Single-Center Experience

Pavan S Upadhyayula et al. Pharmaceutics. .

Abstract

A key limitation to glioma treatment involves the blood brain barrier (BBB). Convection enhanced delivery (CED) is a technique that uses a catheter placed directly into the brain parenchyma to infuse treatments using a pressure gradient. In this manuscript, we describe the physical principles behind CED along with the common pitfalls and methods for optimizing convection. Finally, we highlight our institutional experience using topotecan CED for the treatment of malignant glioma.

Keywords: convection enhanced delivery; glioblastoma; glioma; topotecan.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chronic convection enhanced delivery (CED) of topotecan provides a significant survival advantage. Rats with orthotopic virally-induced, platelet derived growth factor (PDGF) driven tumors were treated with CED of topotecan for various days (1, 4, or 7 days). p-values show a comparison to the PBS control. 1, 4, and 7 days CED survival were each significantly greater than PBS (p < 0.05). The median survival for 7 days CED was significantly greater than the other groups, (median survival: PBS—20 dpi, 1 day—23 dpi, 4 day—31 dpi, 7 day—54 dpi; p < 0.05). The figure is reproduced with permission from [35], Cancer Res. 2011.
Figure 2
Figure 2
CED using a subcutaneous implantable pump is safe and feasible in a large animal model. A schematic demonstration with the sample MRI of convection volume with co-infusion of topotecan and gadolinium is shown demonstrating a sizeable volume of distribution.
Figure 3
Figure 3
Topotecan concentration is correlated with the gadolinium absolute pixel intensity of T1 MRI. Studies were conducted in a porcine model using a subcutaneous pump that co-delivered topotecan and gadolinium. Liquid chromatography-mass spectrometry was used for the quantification of topotecan concentration and correlated with the absolute pixel intensity from T1-weighted MRI. The data are reproduced from D’Amico et al., 2019 [41].
Figure 4
Figure 4
A 71-year-old woman who developed a parietal lobe syndrome on the fourth day of topotecan (TPT) by the CED treatment. Scans are shown at the time of treatment (day 0), at the time the dose limiting toxicity occurred (day 4), 8 weeks after treatment, and 45 weeks after treatment with approximately 90% return to her baseline neurological exam. She was progression free 3 years after the treatment and died just under 4 years post CED.
Figure 5
Figure 5
Diagram outlining the clinical trial parameters for a recently completed Phase IB trial for chronic CED of topotecan in patients with recurrent glioblastoma.
See this image and copyright information in PMC

References

    1. Gill B.J., Pisapia D.J., Malone H.R., Goldstein H., Lei L., Sonabend A., Yun J., Samanamud J., Sims J.S., Banu M., et al. MRI-localized biopsies reveal subtype-specific differences in molecular and cellular composition at the margins of glioblastoma. Proc. Natl. Acad. Sci. USA. 2014;111:12550–12555. doi: 10.1073/pnas.1405839111. - DOI - PMC - PubMed
    1. Yuan J., Levitin H.M., Frattini V., Bush E.C., Boyett D.M., Samanamud J., Ceccarelli M., Dovas A., Zanazzi G., Canoll P., et al. Single-cell transcriptome analysis of lineage diversity in high-grade glioma. Genome Med. 2018;10:1–15. doi: 10.1186/s13073-018-0567-9. - DOI - PMC - PubMed
    1. Stupp R., Mason W.P., van den Bent M.J., Weller M., Fisher B., Taphoorn M.J.B., Belanger K., Brandes A.A., Marosi C., Bogdahn U., et al. Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma. N. Engl. J. Med. 2005;352:987–996. doi: 10.1056/NEJMoa043330. - DOI - PubMed
    1. Walker M.D., Strike T.A., Sheline G.E. An analysis of dose-effect relationship in the radiotherapy of malignant gliomas. Int. J. Radiat. Oncol. 1979;5:1725–1731. doi: 10.1016/0360-3016(79)90553-4. - DOI - PubMed
    1. Lesimple T., Riffaud L., Frappaz D., Ben Hassel M., Gedouin D., Bay J.-O., Linassier C., Hamlat A., Piot G., Fabbro M., et al. Topotecan in combination with radiotherapy in unresectable glioblastoma: A phase 2 study. J. Neuro-Oncol. 2009;93:253–260. doi: 10.1007/s11060-008-9774-3. - DOI - PubMed

LinkOut - more resources