The effect of AGM-1470 in an improved intracranial 9L gliosarcoma rat model

Angiogenesis is a process fundamental to the growth of many solid tumours. Agents that inhibit angiogenesis may have a role in preventing tumour growth. AGM-1470, a synthetic analogue of fumagillin, has been shown to inhibit tumour growth in several extracranial solid tumour models. Its use has been reported to have minimal side effects. No studies have been reported using AGM-1470 in the treatment of an intracranial tumour. To determine the effect of AGM-1470 on an intracranial glial tumour, we used an improved implantation technique to place 80,000 9L tumour cells into the right caudate nucleus of 25 male Fischer 344 rats. Starting on the first post-implantation day, 12 animals received 30 mg kg-1 AGM-1470 via intraperitoneal injection every other day until death. Thirteen control animals received vehicle only. Evidence of intracranial tumour was apparent in 22/23 animals (96%). All animals treated with AGM-1470 experienced a progressive and significant weight loss when compared to controls. At day 17, treated animals retained 80.0 +/- 2.2% of their initial weight, (mean +/- SD) compared to 100.9 +/- 3.6% for controls (p = 2.25 x 10(-12); student's t-test). AGM-1470 had no effect on survival. Median survival in the treatment group was 24.5 days compared to 25 days in the controls (p = 0.95; Mann-Whitney). AGM-1470, although promising in extracranial tumour models, may not be as effective in controlling the growth of intracranial tumours, and its use is not without significant systemic effects. More studies are needed before this drug is used in human brain tumour trials.(ABSTRACT TRUNCATED AT 250 WORDS)