title: Treatment of recurrent malignant glioma by repeated intracerebral injections of human recombinant interleukin-2 alone or in combination with systemic interferon-alpha. Results of a phase I clinical trial.
abstract: Nine patients with a recurrent malignant glioma were treated with repeated intracavitary or intracerebroventricular injections of human recombinant interleukin-2 (rIL-2) alone or in combination with systemic interferon-alpha (IFN-alpha). Five patients received only rIL-2 and four were treated with rIL-2 plus subcutaneous injections of IFN-alpha. Therapy was administered on a Monday, Wednesday, Friday schedule for up to 10 weeks, beginning with a dose of 10,000 IU rIL-2/injection. Doses were escalated every two weeks until some toxicity was apparent. The maximum amount of rIL-2 any one patient in this group received was 580,000 IU. Patients on combination immunotherapy were held at an rIL-2 dosage of 10,000 IU while IFN-alpha, which began at 3 million IU, was escalated every other week up to 18 million IU/dose. They were then held at that IFN-alpha dosage and rIL-2 was increased to 50,000 IU. The total amount of rIL-2 and IFN-alpha any one in this group received was 510,000 IU and 417 million IU, respectively. Repeated injections of 10,000 IU rIL-2 were well-tolerated by all nine patients and no change in their functional status was seen. At doses at 50,000 IU rIL-2, increased edema around the tumor cavity was observed by MRI/CT scand in 3/5 patients and clinical side-effects in the form of somnolence and headache along with some morbidity specifically associated with tumor location were also seen. Patients receiving rIL-2+ IFN-alpha showed progressive fatigue, muscle weakness, and occasionally nausea. Two of these patients showed increased peritumoral edema on MRI/CT scan.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond.
authors.forename: R E
authors.initials: RE
authors.lastname: Merchant
authors.forename: D W
authors.initials: DW
authors.lastname: McVicar
authors.forename: L H
authors.initials: LH
authors.lastname: Merchant
authors.forename: H F
authors.initials: HF
authors.lastname: Young
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000601:surgery / Q000628:therapy*; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging / Q000601:surgery / Q000628:therapy*; D006801:Humans; D007267:Injections; D007276:Injections, Intraventricular; D007370:Interferon Type I / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D008297:Male; D009364:Neoplasm Recurrence, Local; D011994:Recombinant Proteins / Q000627:therapeutic use / Q000633:toxicity; D014057:Tomography, X-Ray Computed
chemical_list: D007370:Interferon Type I; D007376:Interleukin-2; D011994:Recombinant Proteins