Poor drug distribution as a possible explanation for the results of the PRECISE trial

John H. Sampson, Gary Archer, Christoph Pedain, Eva Wembacher-Schröder, Manfred Westphal, Sandeep Kunwar, Michael A. Vogelbaum, April Coan, James E. Herndon, Raghu Raghavan, Martin L. Brady, Davi D A Reardon, Allan H. Friedman, Henry S. Friedman, M. Inmaculada Rodríguez-Ponce, Susan M. Chang, Stephan Mittermeyer, Davi Croteau, Raj K. Puri, James Mac Dowell MarkertMichael Prados, Thomas Chen, Adam Mamelak, Timothy Cloughesy, John Yu, Kevin Lillehei, Joseph Piepmeier, Edward Pan, Frank Vrionis, H. Lee Moffitt, Jeffrey Olson, James Chandler, Nina Paleologos, Richard W. Byrne, Maciej Lesniak, Jon D. Weingart, Peter Black, Tom Mikkelsen, Joon Uhm, Richard Bucholz, Lauren Abrey, Theodore H. Schwartz, Jeffrey Bruce, Anthony Asher, Stephen Tatter, Gene Barnett, Antonio E. Chiocca, Johnny B. Delashaw, Kevin Judy, Sunil Patel, Bruce Frankel, Fred Lang, Pamela New, Karen Fink, Randy L. Jensen, Mark Shaffrey, Lynne Taylor, Warren Boling, Behnam Badie, Abhijit Guha, Vivek Mehta, Mark Hamilton, David D. Eisenstat, Farhad Pirouzmand, David Macdonald, Rolando Del Maestro, Daryl Fourney, Maximilian Mehdorn, Roland Goldbrunner, Gabriele Schackert, Andreas Unterberg, Zvi Ram, Zvi Cohen, Zvi Rappaport, Jan Jacob Mooij, John G. Wolbers, Peter Warnke, Varnavas Papanastassiou

Research output: Contribution to journalArticlepeer-review

210 Scopus citations


Object. Convection-enhanced delivery (CED) is a novel intracerebral drug delivery technique with considerable promise for delivering therapeutic agents throughout the CNS. Despite this promise, Phase III clinical trials employing CED have failed to meet clinical end points. Although this may be due to inactive agents or a failure to rigorously validate drug targets, the authors have previously demonstrated that catheter positioning plays a major role in drug distribution using this technique. The purpose of the present work was to retrospectively analyze the expected drug distribution based on catheter positioning data available from the CED arm of the PRECISE trial. Methods. Data on catheter positioning from all patients randomized to the CED arm of the PRECISE trial were available for analyses. BrainLAB iPlan Flow software was used to estimate the expected drug distribution. Results. Only 49.8% of catheters met all positioning criteria. Still, catheter positioning score (hazard ratio 0.93, p = 0.043) and the number of optimally positioned catheters (hazard ratio 0.72, p = 0.038) had a significant effect on progression-free survival. Estimated coverage of relevant target volumes was low, however, with only 20.1% of the 2-cm penumbra surrounding the resection cavity covered on average. Although tumor location and resection cavity volume had no effect on coverage volume, estimations of drug delivery to relevant target volumes did correlate well with catheter score (p >0.003), and optimally positioned catheters had larger coverage volumes (p < 0.002). Only overall survival (p = 0.006) was higher for investigators considered experienced after adjusting for patient age and Karnofsky Performance Scale score. Conclusions. The potential efficacy of drugs delivered by CED may be severely constrained by ineffective delivery in many patients. Routine use of software algorithms and alternative catheter designs and infusion parameters may improve the efficacy of drugs delivered by CED.

Original languageEnglish (US)
Pages (from-to)301-309
Number of pages9
JournalJournal of neurosurgery
Issue number2
StatePublished - Aug 2010


  • Brain neoplasm
  • Convection-enhanced delivery
  • Drug delivery system
  • Interleukin-13
  • Planning software

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery


Dive into the research topics of 'Poor drug distribution as a possible explanation for the results of the PRECISE trial'. Together they form a unique fingerprint.

Cite this