The abstract I posted earlier was the preliminary one submitted to ASCO. The following abstract was presented:
Phase I Results of Intra-Tumoral Infusion of I-131 ch-TNT-1/B in the Treatment of Recurrent Malignant Gliomas. Sunil J. Patel, Ken Spicer, Pamela VanTassel, Stephen Haines, Leonnie Gordon, Art Frankel, Jamie Oliver. Techniclone Corporation, Tustin, CA.
TNT-1/B is an iodine-131 complexed chimeric antibody targeted to the DNA/histone complex. The antibody binds to exposed antigen and delivers a collateral ionizing radiation to surrounding tumor cells.
Nine patients with recurrent glioblastoma multiforme and 3 with recurrent anaplastic astrocytoma were enrolled in a dose-escalating phase I study using intra-tumoraly administered TNT-1/B. Study drug was infused over 24 hours. Six patients received fixed doses of TNT-1/B and were given both imaging and therapeutic doses to assess radiation dosimetry and biodistribution. The remaining six patients were treated with single individualized doses estimated to deliver 15,000 (N=4) or 22,500 cGy (N=2) to the gadolinium enhancing tumor volume (GETV). GETV ranged from 27-180 cc. all patients were treated with steroids both pre- and post-therapy. No patient received tumor debulking prior to TNT-1/B therapy.
Radiation dosimetry from the first six patients estimated doses of radiation from 700-13000 cGy to the tumor with doses of 20-40 mCi of the drug. Initial estimates also indicated 34 (+/-9)% dose retention at 24 hours with an effective half-life of 45.5 (+/-15)hours. Non-target organ doses of radiation were well below toxicity levels. One case of thrombocytopenia at 30 days. To date 6 of 9 patients had stabilization of the tumor at 60 days follow-up. SPECT/MR image merging indicated drug distribution targeted to GETV. Median time to progression for GBM and AA is 10.6 and 27.3 weeks, respectively. Median survival time is 23.0 and 41.9 weeks for GBM and AA, respectively.
Anti-tumor activity and targeted drug distribution have been shown with minimal systemic or local toxicity.
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