PREVENTION OF GALLIUM TOXICITY BY HYPERHYDRATION IN TREATMENT OF MEDULLOBLASTOMA

In vitro and in vivo studies have established gallium nitrate as an ef fective chemotherapeutic agent against human medulloblastoma. In vitro , gallium nitrate reduced cell proliferation and DNA synthesis of medu lloblastoma Daoy. Gallium inhibits the availability of Fe-59 to ribonu cleotide reductase and has a direct effect on the enzyme itself. In vi vo, gallium demonstrated similar effects on the medulloblastoma Daoy c ell line in nude mice. Tumor growth rate and actual size were decrease d; however, severe nephrotoxicity and mortality were observed. In our study, intradermal injections of medulloblastoma Daoy cells were given to nude mice and then tumors were allowed to grow. Tumor-bearing mice received a 15-day gallium (50 mg/kg/day) regimen, 20-day rest, 7-day gallium (66.5 mg/kg/day) dose escalation regimen beginning when tumor size exceeded 8-10 mm in diameter. All treated and control mice receiv ed saline hyperhydration during both treatment sessions. Our study res ulted in the prevention of severe toxicity and an inhibition of tumor growth. No toxicity occurred with gallium nitrate at 50 mg/kg/day. Sev ere morbidity and mortality were observed at the higher gallium dose l evel (66.5 mg/kg/day), suggesting that the 50 mg/kg/day dose is the ap propriate level when investigating gallium nitrate as a chemotherapeut ic agent in nude mice.