Intracerebral infusion of an EGFR-targeted toxin in recurrent malignant brain tumors.
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
Duke Scholars
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Related Subject Headings
- Transforming Growth Factor alpha
- Tomography, Emission-Computed, Single-Photon
- Oncology & Carcinogenesis
- Neoplasm Recurrence, Local
- Middle Aged
- Maximum Tolerated Dose
- Magnetic Resonance Imaging
- Injections, Intraventricular
- Immunotoxins
- Humans
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Transforming Growth Factor alpha
- Tomography, Emission-Computed, Single-Photon
- Oncology & Carcinogenesis
- Neoplasm Recurrence, Local
- Middle Aged
- Maximum Tolerated Dose
- Magnetic Resonance Imaging
- Injections, Intraventricular
- Immunotoxins
- Humans