Dianhydrogalactitol and neural tumors: an in vitro, in vivo preclinical evaluation.
The effects of dianhydrogalactitol on human neuroblastomas in vitro and in vivo as heterotransplants in nude mice were determined. Four neuroblastoma lines and three primitive neuroectodermal tumor lines were found, in vitro, to have different sensitivities to the drug. The most sensitive in in vitro assays was the neuroblastoma line SK-N-Mc. Tumors from patients resistant to cyclophosphamide were sensitive to dianhydrogalactitol in vitro and in nude mice. The lack of increased cytotoxicity in vitro with concentrations greater than 12 micrograms/ml and the lowered degree of weight loss in mice treated with 6 mg/kg/day x 5 consecutive days compared to 15 mg/kg/day x 2 days (either in sequence or with a 3-day interval) suggest that clinical trials with 5-day courses or constant infusions may be more effective than intermittent pulsed doses.
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003520:Cyclophosphamide / Q000627:therapeutic use; D003961:Dianhydrogalactitol / Q000627:therapeutic use* / Q000633:toxicity; D004353:Drug Evaluation, Preclinical; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology; D013402:Sugar Alcohols / Q000627:therapeutic use*; D013997:Time Factors; D014183:Transplantation, Heterologous
D013402:Sugar Alcohols; D003961:Dianhydrogalactitol; D003520:Cyclophosphamide