Publications [#148373] of James M Provenzale

Papers Published

1. JH Sampson, G Akabani, GE Archer, MS Berger, RE Coleman, AH Friedman, HS Friedman, K Greer, JE Herndon 2nd, S Kunwar, RE McLendon, A Paolino, NA Petry, JM Provenzale, DA Reardon, TZ Wong, MR Zalutsky, I Pastan, DD Bigner, Intracerebral infusion of an EGFR-targeted toxin in recurrent malignant brain tumors., Neuro-oncology, vol. 10 no. 3 (June, 2008), pp. 320-9, ISSN 1522-8517 [doi]
   (last updated on 2013/05/13)

   Abstract:
   The purpose of this study is to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and intracerebral distribution of a recombinant toxin (TP-38) targeting the epidermal growth factor receptor in patients with recurrent malignant brain tumors using the intracerebral infusion technique of convection-enhanced delivery (CED). Twenty patients were enrolled and stratified for dose escalation by the presence of residual tumor from 25 to 100 ng/ml in a 40-ml infusion volume. In the last eight patients, coinfusion of (123)I-albumin was performed to monitor distribution within the brain. The MTD was not reached in this study. Dose escalation was stopped at 100 ng/ml due to inconsistent drug delivery as evidenced by imaging the coinfused (123)I-albumin. Two DLTs were seen, and both were neurologic. Median survival after TP-38 was 28 weeks (95% confidence interval, 26.5-102.8). Of 15 patients treated with residual disease, two (13.3%) demonstrated radiographic responses, including one patient with glioblastoma multiforme who had a nearly complete response and remains alive >260 weeks after therapy. Coinfusion of (123)I-albumin demonstrated that high concentrations of the infusate could be delivered >4 cm from the catheter tip. However, only 3 of 16 (19%) catheters produced intraparenchymal infusate distribution, while the majority leaked infusate into the cerebrospinal fluid spaces. Intracerebral CED of TP-38 was well tolerated and produced some durable radiographic responses at doses Keywords:
   Adult • Aged • Antineoplastic Agents • Brain Neoplasms • Exotoxins • Humans • Immunotoxins • Injections, Intraventricular • Magnetic Resonance Imaging • Maximum Tolerated Dose • Middle Aged • Neoplasm Recurrence, Local • Receptor, Epidermal Growth Factor • Tomography, Emission-Computed, Single-Photon • Transforming Growth Factor alpha • administration & dosage* • adverse effects • antagonists & inhibitors* • drug therapy*