Disease relevance of KU 2285

• All patients tolerated KU-2285 well, and no drug-related toxicity was observed [1].
• Eleven patients with unresectable but localized pancreatic cancer treated with KU-2285 plus IORT and external beam radiotherapy had a median survival time of 11 months and 1-year local control rate of 50%, which compares favourably with those of 8 months (P = 0.26) and 28% (P = 0.10) for 22 matched historical control patients [1].
• In vivo-in vitro study: the sensitizer enhancement ratios of etanidazole and KU-2285 were 1.18 and 1.31, respectively, in the micronucleus assay, and 1.16 and 1.42 in the chromosomal aberration assay [2].

High impact information on KU 2285

• A fluorinated 2-nitroimidazole radiosensitizer KU-2285 was given before intraoperative radiotherapy (IORT) to 30 patients with unresectable, unresected or macroscopic residual tumours [1].
• Radiosensitizing activity and pharmacokinetics of multiple dose administered KU-2285 in peripheral nerve tissue in mice [3].
• CONCLUSION: KU-2285 was more effective than SR-2508 both at low drug concentrations in vitro and at low drug doses in vivo [4].
• Labeled 3H-2-deoxyglucose studies showed that RP-170 neither markedly affected the uptake of total radioactivity into the brain nor its degree of phosphorylation whereas, KU-2285 (2 g/kg) and RK-28 (1 g/kg) decreased uptake by approximately 50% and phosphorylation approximately 3 and 4-fold, respectively [5].
• The pharmacokinetics in the sciatic nerves were undertaken, when KU-2285 or etanidazole were injected at a dose of 200 mg/kg intravenously one, two, three or four times at 2-h intervals [3].

Biological context of KU 2285

• Under hypoxic conditions, the sensitizer enhancement ratio (SER) determined at 1% cell survival level for sanazole, nimorazole and KU-2285 was 1.55, 1.45 and 1.95, respectively, at 1 mM, and 1.40, 1.40 and 1.75, respectively, at 0.5 mM [6].
• Combined effects of tirapazamine and irradiation on the hypoxic cells were much higher than the radiation effect on aerobic cells at low doses, while the effects of KU-2285 did not exceed that of aerobic irradiation [7].

Gene context of KU 2285

• METHODS AND MATERIALS: KU-2285 was tested in comparison with SR-2508 at low concentrations (0.05-0.25 mM) in vitro by the cytokinesis-block micronucleus assay and by the colony formation assay, and at low drug doses (12.5-50 mg/kg) in vivo by the in vivo-in vitro assay and by the growth delay assay using SCC VII tumors in C3H/He mice [4].

Analytical, diagnostic and therapeutic context of KU 2285

• A phase I/II study of a hypoxic cell radiosensitizer KU-2285 in combination with intraoperative radiotherapy [1].
• In vivo radiosensitizing activity of a new fluorinated hypoxic cell radiosensitizer, KU-2285, in combination with radiation dose fractionation [8].
• After treatment with KU-2285 and 12 Gy, the HF was 25% at 6 h, 32% at 12 h, 24% at 24 h, and 7.6% at 72 h [9].
• KU-2285 had a definite radiosensitizing effect even at low radiation doses, and clinical trials of KU-2285 may be warranted [10].
• PURPOSE: Since the radiosensitizing effect of KU-2285 at relatively low dose levels is not known, we investigated its efficacy at such low concentrations or doses achievable in humans with oral administration of 0.3-1.0 g/m2 [4].

References