Effects of ACNU and radiotherapy on malignant glioma

Abstract

A randomized clinical study of irradiation and irradiation combined with ACNU in the treatment of malignant gliomas was performed in order to determine if there was an enhancing therapeutic effect of ACNU given in addition to radiotherapy. An effect was defined as a reduction in tumor size, changes in neurological signs and performance status within 1 month after the completion of radiotherapy, or statistically improved survival times. Seventy-seven patients from 14 neurosurgical clinics were included in this validated study group. Radiotherapy with a total dose of 5000 to 6000 rads, given in 25 to 30 subdoses, was applied to the whole brain and to a generous field surrounding the tumor. Patients who were assigned to receive chemotherapy were given ACNU intravenously once or twice during radiotherapy at a dose of 100 mg/sq m of body surface area. The response rate (more than 50% reduction of the tumor size) was 13.5% in the group treated by radiotherapy alone and 47.5% in the group with radiotherapy and ACNU. The hematological toxicity was more severe in the group treated with radiotherapy and ACNU. Other toxicity was mild and acceptable. The survival rates of patients with astrocytoma grade III and glioblastoma multiforme at 36 months after the surgery were 48.9% and 0% for radiotherapy alone and 59.0% and 16.3% for radiotherapy plus ACNU, respectively. The differences between the survival curves were not significant at the p = 0.05 level. This study has demonstrated that, although the use of ACNU during radiotherapy suppressed malignant gliomas more than radiotherapy alone, the survival time was not extended significantly. It is necessary to continue to search for an effective chemotherapeutic regimen to prolong survival of patients with malignant gliomas.

Antitumor effect and cellular immunity activation by murine interferon-β gene transfer against intracerebral glioma in mouse

“…[4][5][6] As chemotherapeutic agents, nitrosoureas such as ACNU and MCNU are considered most effective against malignant glioma. 17,18 HuIFN-␤ can behave as a drug or radiation sensitizer, enhancing toxicity against gliomas and a variety of neoplasms when given in combination with chemotherapeutic agents such as nitrosoureas. 6 Cationic liposome-mediated HuIFN-␤ gene transfer results in a much stronger inhibition of glioma cell growth than does exogenous HuIFN-␤.…”

Patterns of Intracranial Glioblastoma Recurrence After Aggressive Surgical Resection and Adjuvant Management: Retrospective Analysis of 43 Cases

“…Nevertheless, the incidences of recurrence, regrowth, and dissemination of the tumor are very high due to the well-known infiltrative extension far beyond the boundaries of the localized lesion identifiable with neuroimaging. 4,20,33,37,48) The progression of glioblastoma after treatment in up to 97% of cases occurs either from the bulk of the mass or within 20 mm from the border of its enhanced part identifiable on T 1 -weighted magnetic resonance (MR) imaging, and the presence of such local recurrence may be associated with impaired prognosis. 2,3,12,13,23,25,32,34,35,43,44,54) Therefore, various methods for improvement of tumor control at the time of both initial and salvage treatment have been proposed, such as inclusion of the marginal brain tissue in the high dose area during FRT, 4,17,20,26,31-33, 35,49,50) additional dose boost with stereotactic radiosurgery, 14,18,41) brachytherapy, 10,36,43) implantation of Gliadel wafers (Guilford Pharmaceuticals Inc., Baltimore, Maryland, USA), 53) or various types of intralesional immunotherapy.…”

Standard Therapy for Glioblastoma- A Review of Where We Are

“…1-(4-Amino-2-methyl-5-pirimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) was widely used based on a small randomized study in Japan in the 1980s. 26) The response rate was better in the combined treatment arm with ACNU and radiotherapy (47.5% in the combined treatment arm, 13.5% in the simple radiotherapy arm), but the OS was not significantly different (median OS was 14 months and 12 months, respectively). Although the combined therapy with ACNU and radiotherapy was promising, a randomized phase 3 study had not been performed.…”