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Treatment of recurrent malignant glioma by repeated intracerebral injections of human recombinant interleukin-2 alone or in combination with systemic interferon-α. Results of a phase I clinical trial

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Summary

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-α (IFN-α). Five patients received only rIL-2 and four were treated with rIL-2 plus subcutaneous injections of IFN-α. 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-α, which began at 3 million IU, was escalated every other week up to 18 million IU/dose. They were then held at that IFN-α dosage and rIL-2 was increased to 50,000 IU. The total amount of rIL-2 and IFN-α any one in this group received was 510,000IU 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-α showed progressive fatigue, muscle weakness, and occasionally nausea. Two of these patients showed increased peritumoral edema on MRI/CT scan. Neither hematological abnormalities nor changes from baseline values were seen in blood samples from any of the patients. MRI/CT scans made at the conclusion of immunotherapy indicated tumor progression in two of the patients treated with rIL-2 alone while no tumor growth at the site of treatment occurred in the other two or in the four treated with the combination of rIL-2 and IFN-α. Further clinical testing of rIL-2 in combination with IFN-α is indicated.

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Merchant, R.E., McVicar, D.W., Merchant, L.H. et al. Treatment of recurrent malignant glioma by repeated intracerebral injections of human recombinant interleukin-2 alone or in combination with systemic interferon-α. Results of a phase I clinical trial. J Neuro-Oncol 12, 75–83 (1992). https://doi.org/10.1007/BF00172459

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