289. Adenoviral-Mediated p53 Gene Therapy (Advexin) in a Patient with Li-Fraumeni Syndrome with a Mixed Germ Cell Tumor: Tolerability and Response

Abstract

Li-Fraumeni syndrome is an autosomal dominant disorder characterized by familial clustering of malignancies, predominantly sarcomas, breast cancer, brain tumors and adrenocortical carcinoma; an inordinate pattern of multiple primaries; and occurrence at a young age. Approximately 70% of the cases can be attributed to TP53 germ-line mutation 73% of which are located in the coding regions of exons 5 to 8. The index patient is a 25 year old woman presenting in 2002 with abdominal pain, anorexia and vomiting leading to the diagnosis of granulosa cell tumor confirmed by IHC-the second such case reported with the syndrome. TP53 sequencing showed 151delG, a frameshift mutation in exon 4. The mutation results in a stop codon downstream. Results of IHC for gene expression are pending. She was initially treated with bleomycin, cisplatin and velban. Following recurrence in 2004, the patient was received Ifosfamide, cisplatin and etoposide followed by the substitution of paclitaxel for Ifosfamide after development of encephalopathy. Disease progression eventuated in pelvic radiation and, with the development of CNS metastases, whole brain radiation.