Enhancement of the antitumor efficacy of lomustine by the radiosensitizer RSU 1069.
Previous investigations have shown that combining the radiation sensitizer misonidazole with conventional alkylating chemotherapeutic agents can lead to a therapeutic advantage. More recently, another sensitizer, RSU 1069, has been reported to give an enhancement of antitumor agent efficacy similar to that observed with misonidazole, but at an approximately tenfold lower sensitizer dose. One chemotherapeutic agent whose activity has been modified by sensitizers to a greater extent in tumors than in critical normal tissues is the nitrosourea lomustine (CCNU). The present studies evaluated the therapeutic benefit of combining RSU 1069 and CCNU in KHT sarcoma-bearing C3H/HeJ mice. The drugs were administered ip, and tumor response was assessed by measuring the survival of clonogenic KHT cells 22-24 hours after treatment. Normal tissue toxicity was determined using peripheral wbc counts 3 days after treatment and a 30-day lethality assay. Combining CCNU with a 0.38-mmol/kg dose of RSU 1069 increased tumor cell killing by a factor of approximately 1.9. Wbc toxicity and 30-day animal lethality increased with CCNU dose, but the addition of RSU 1069 enhanced either endpoint only slightly (factor of 1.0-1.2). The addition of RSU 1069 to CCNU treatment, therefore, led to a significant therapeutic benefit.
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D007928:Lethal Dose 50; D008130:Lomustine / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D008809:Mice, Inbred C3H; D008920:Misonidazole / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D011837:Radiation-Protective Agents / Q000008:administration & dosage* / Q000633:toxicity; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology
D011837:Radiation-Protective Agents; D008130:Lomustine; C041712:1-(2-nitro-1-imidazolyl)-3-aziridino-2-propanol; D008920:Misonidazole