Abstract
e17501 Background: Esophageal toxicity has been accepted reluctantly, as a necessary side effect of the benefits of chemoradiotherapy for lung cancer. MnSOD is a genetically engineered therapeutic DNA/liposome containing the human MnSOD transgene. Preclincial studies in mouse models have demonstrated that the expression of the human MnSOD transgene confers protection of normal tissues from ionizing irradiation damage. Methods: Chemotherapy (carboplatin AUC=2 and paclitaxel 45 mg/m2 intravenously) was given weekly (for 7 weeks), concurrently with radiation therapy for pts with locally advanced NSCLC. MnSOD PL was swallowed twice a week (total 14 doses), at 3 dose levels: 0.3, 3, and 30 mg. Dose escalation followed a standard phase I design. Esophagoscopy was done at baseline, day 4 and 6 weeks after radiation with biopsies of the squamous lining cells. DNA was extracted and analyzed by PCR for the detection of the MnSOD transgene DNA. Results: Nine patients with stage IIIA (2) and IIIB (7) completed the course of therapy per study protocol. Five had squamous histology, 2 adenocarcinoma, and 2 not specified. These patients were treated in 3 different cohorts at 3 dose levels of MnSOD PL: 0.3, 3, and 30 mg. The median dose of radiation was 77.7Gy (range 63-79.10Gy). Overall response rate for the standard chemo-radiation regimen was 67% (n=9). Grade 2 dyspepsia and a grade 1 rash in one patient was considered possibly related to MnSOD PL. None of the other reported toxicities were considered possibly, probably, or definitely related to MnSOD PL. There were no dose-limiting toxicities reported in all 3 dosing tiers. MnSOD PCR product was not detected in the esophageal samples. Conclusions: The oral administration of MnSOD PL is feasible and safe. The phase II recommended dose is 30 mg. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Valentis, Inc.
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