Results of a pilot study involving the use of an antisense oligodeoxynucleotide directed against the insulin-like growth factor type I receptor in malignant astrocytomas

Purpose: Preclinical animal experiments support the use of an antisense oli godeoxynucleotide directed against the insulin-like growth factor type I re ceptor (IGF-IR/AS ODN) as an effective potential antitumor agent. We perfor med a human pilot safety and feasibility study using an IGF-IR/AS ODN strat egy in patients with malignant astrocytoma. Patients and Methods: Autologous glioma cells collected at surgery were tre ated ex vivo with an IGF-IR/AS ODN, encapsulated in diffusion chambers, rei mplanted in the rectus sheath within 24 hours of craniotomy, and retrieved after a 24-hour in situ incubation. Serial posttreatment assessments includ ed clinical examination, laboratory studies, and magnetic resonance imaging scans. Results: Other than deep venous thrombosis noted in some patients, no other treatment-related side effects were observed. IGF-IR/AS ODN-treated cells, when retrieved and assessed, were less than or equal to 2% intact by trypa n blue exclusion, and none of the intact cells were viable in culture there after. Parallel Western blots disclosed IGF-IR downregulation to less than or equal to 10% after ex vivo antisense treatment. At follow-up, clinical a nd radiographic improvements were observed in eight of 12 patients, includi ng three cases of distal recurrence with unexpected spontaneous or postsurg ical regression at either the primary or the distant intracranial site. Conclusion: Ex vivo IGF-IR/AS ODN treatment of autologous glioma cells indu ces apoptosis and a host response in vivo without unusual side effects. Sub sequent transient and sustained radiographic and clinical improvements warr ant further clinical investigations. (C) 2001 by American Society of Clinic al Oncology.