A novel drug to reduce tumor perfusion: antitumor effect alone and with hyperthermia

We have investigated the feasibility of enhancing damage induced by hyperthermia in SCK murine tumors by reducing tumor blood perfusion using a new agent, KB-R8498. Within several minutes of an i.v. injection, the tumor perfusion was reduced to less than 20% of the control value, and it recovered to 40-70% of the control value by 1 h after injection. The perfusion in normal tissues decreased or increased soon after drug administration depending on the tissue type. However, by 1 h after drug treatment, perfusion in five of the seven tissues examined had returned to the control level. The tumor pH was also reduced after i.v. drug administration. Control tumors grew to four times the initial volume in 6 days. Tumors that were heated at 42.5 degrees C for 60 min were delayed in growth by 4 days compared to control tumors. There was a growth delay of 14 days when an i.v. injection of KB-R8498 was given and the tumors were heated at 42.5 degrees C either immediately or 1 h later. In drug-alone studies, the tumor growth was delayed by 4 days when the drug was infused continuously at a rate of 30-50 mg/kg day(-1) for 7 days or about 2 days when mice were treated with five daily injections of 30 mg/kg KB-R8498.