Aziridinylbenzoquinone in recurrent, progressive glioma of the central nervous system. A phase ii study by the illinois cancer council

Abstract

Aziridinylbenzoquinone (AZQ) was studied in a Phase II protocol for persons with glioma of the central nervous system (CNS) recurrent or progressive after surgery and radiotherapy. Patients received AZQ, 30 mg/m2 intravenously every 3 weeks if previously untreated or 27.5 mg/m2 if previously exposed to cytotoxic drugs. Partial response was defined as a reduction of at least 50% reduction in the product of the two longest perpendicular diameters of the indicator lesion persisting for a minimum of 28 days. Twenty-eight patients are evaluable for response at this time. Objective response (OR) occurred in four (14.3%): two complete and two partial. Stabilization of disease (SD) was seen in 7 (25.0%). Median survival, in weeks, was greater than 46.0 for responders, 41.7 for SD, and 19.3 for those with progressive disease. The survival experiences are significantly different (P = 0.030 [Breslow]). The OR rate was 21.1% in 19 without prior chemotherapy and 0% in 9 previously treated patients. There were two AZQ-related deaths in patients with prior exposure to nitrosoureas (1 CNS hemorrhage; 1 aspiration pneumonia). One patient had an anaphylactic reaction. Three patients whose tumor initially increased in size subsequently had marked tumor shrinkage. AZQ is an active agent that must be used with added caution in patients who have received nitrosoureas. Initial tumor enlargement may precede response. Although response appears to prolong survival, the correlation between stabilization of disease and survival is not well-defined.

A phase II study of diaziquone in children with recurrent or progressive primary brain tumors: A report from the Childrens Cancer Study Group

“…They were treated with various dosage schedules, including a five consecutive day regimen as reported herein, a three or four weekly schedule, a daily times two dose schedule, and a day one and eight schedule. Neither the total dose of AZQ administered per course nor the dosage regimen appears to have an impact on the response rate, although there are no comparative trials [1][2][3][4][5][6][7][8][9][10][11].…”

“…The responses by diagnosis are listed in Table 2. Prolonged stable disease while on therapy with AZQ was seen in four patients with ependymoma (6,8,12, and 18 months), two patients with PNET (10+ and 27+ months), and one patient with medulloblastoma (8 months). A 3 3/4 year old patient with an ependymoma of the fourth ventricle was placed on AZQ when he developed intracranial metastases in the right frontal horn and the inferior aspect of the third ventricle.…”

“…Prior phase I studies of AZQ in children and phase I and II studies in adults with brain tumors demonstrated activity in anaplastic astrocytoma, glioblastoma multiforme and medulloblastoma [1][2][3][4][5][6][7][8][9][10]. Based on the activity of AZQ in preclinical studies and phase I and II data available at the time in human brain tumors, a phase II study of AZQ in children was begun in March 1983 and closed in October 1986.…”

Improving vaccine efficacy against malignant glioma

“…[7][8][9] In the absence of therapy, OS is limited to 30-35 weeks. [10][11][12][13] The poor outcome for GBM patients is largely due to the molecular and cellular heterogeneity of the cancer, which equips the tumor with multiple strategies for adapting to and overcoming the effects of therapy.…”

Clinical applications of quinone-containing alkylating agents

“…A number of clinical trials showed response rates of approximately 20% in patients with high-grade or progressive gliomas treated with diaziquone (148,149) and approximately 25% in patients with astrocytic neoplasms treated with diaziquone and either BCNU or procarbazine (150). However, phase III trials comparing diaziquone to the nitrosoureas, BCNU or PCNU, found that diaziquone was not significantly better than BCNU (151) and was less effective than PCNU (152) in patients with brain tumors.…”