The
radiation sensitizer misonidazole (MISO) has been shown to potentiate the cytotoxic action of a variety of anti-
cancer agents. Even larger enhancement ratios than those observed with MISO have been found with certain other
nitroimidazoles. One agent reported to be particularly effective in combination with the chemotherapeutic agent
melphalan is the sensitizer
RSU 1069. The present studies therefore were designed to evaluate the effect of combining these two agents in the treatment of intramuscularly growing KHT
sarcomas.
Tumor response was assessed using an in vivo to in vitro clonogenic cell survival assay. When given at times ranging from 60 min before to 30 min after
melphalan exposure,
RSU 1069 was found to increase the tumoricidal activity of the chemotherapeutic agent. Complete dose response curves combining
RSU 1069 and a range of
melphalan doses then were determined. For comparison the effects of combining MISO or
benznidazole (BENZO) with
melphalan also were evaluated. All sensitizers were administered i.p. either 30 min before (BENZO) or simultaneously with (MISO,
RSU 1069) the chemotherapeutic agent. Survival of clonogenic
tumor cells assessed 22 to 24 hr
after treatment was used to assay
tumor response. When combined with
melphalan, doses of
RSU 1069 (0.38 mmol/kg), BENZO (0.3 mmol/kg) and MISO (5.0 mmol/kg) were found to yield dose modifying factors of 1.6, 1.5, and 1.4, respectively. These results indicate that potentiation of
melphalan activity occurs at
RSU 1069 doses which are approximately 10-fold lower than those of MISO, making this sensitizer as effective a potentiator of
melphalan as so far tested in the KHT
sarcoma.