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Please note: This article is part of the Cancer Center's News Archive and is here for historical purposes. The information and links may no longer be up-to-date.

Michigan Oncology Journal Fall 98

Of Interest

New Clinical Trials for Sarcoma Patients

We have initiated a randomized phase II trial for patients with local high-grade sarcomas suitable for adjunctive chemotherapy or patients with disseminated sarcoma to receive doxorubicin with either Ifosfamide at 6 Gm/m2 and mesna or 12 Gm/m2 and doxorubicin. In addition to answering a dose-intensity question, we also will measure the relationship of a phenotypic measurement of Cytochrome P450 34A (CYP 34A) utilizing the erythromycin breath test (ERMBT) and the central nervous system (CNS) toxicity of Ifosfamide. The major determinant of the metabolic pathway of ifosfamide is this specific CYP 34A metabolizing enzyme. In order to try and prevent the CNS toxicity, we will try to down regulate the activity of this enzyme using troleandomycin as a substrate. Patients specifically eligible for this protocol include those with histological documented AJCC Stage IIIb (Grade 3 lesions and greater than 5 cm in widest diameter) or AJCC Stage IIb deep to the superficial fascia or documented high-grade sarcoma.

We are conducting a phase II trial of GM-CSF (sargramostim) as treatment for locally advanced or metastatic soft tissue sarcomas. While there have been few studies evaluating GM-CSF, one study using molgramostine (the E.coli derived factor) in addition to modest chemotherapy suggests benefit from GM-CSF itself. The drug is adminstered as daily doses for 14 days every 21 days for 48 weeks.

In conjunction with Dr. Gary Nabel (Director, University of Michigan Gene Therapy Program), we will initiate a phase I trial of gene therapy using a modified Fas ligand with a smooth muscle promotor in an adenoviral vector in patients with locally advanced or metastatic leiomyosarcoma or gastrointestinal stromal tumors. This gene therapy will be administered via intra-arterial injection. The driving hypothesis for this new approach is that we can enlist the immune system to attack the tumor by infecting the tumor cells with an adenovirus containing modified gene for Fas ligand. Fas (fibroblast associated) is a type I receptor including tumor necrosis factor and nerve growth factor. We have joined the modified FasL gene to a smooth muscle specific promotor. The goal of this is to restrict the expression of the gene to the cells of tumors that show smooth muscle differentiation such as leiomyosarcoma and other bony and soft tissue sarcomas.

A second gene therapy initiative in conjunction with Dr. Nabel uses the same modified gene but this time uses an RSV (Rous sarcoma virus) as the promotor. This therapy is being developed for low-grade but locally quite advanced sarcomas such as a desmoid tumor (fibromatosis). This gene will be administered by direct injection by Dr. Sybil Biermann, an orthopedic oncologist.

We have submitted an application to the National Gene Vector Laboratory to make both these genes.

 

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Please note: The articles listed in the Cancer Center's News Archive are here for historical purposes. The information and links may no longer be up-to-date.