Effect of the Hypoxic Cell Sensitizer Isometronidazole on Local Control of Two Human Squamous Cell Carcinomas after Fractionated Irradiation

Abstract

ISO at a concentration of 750 mg/kg b.w. shows an efficacy as a hypoxic cell sensitizer in severely hypoxic FaDu tumors but not in less hypoxic GL tumors. This supports the principle of hypoxic cell sensitization and improvement of local control of hypoxic tumors by nitroimidazole derivatives. However, doses of 750 mg/kg b. w. before each fraction may be difficult to achieve in the clinical situation. This, in light of the fact that other well-tolerable hypoxic cell sensitizers such as nimorazole with clinically proven efficacy at daily oral doses of < 3 g are available, limits the potential usefulness of ISO for radiation oncology.

Technical Improvement of pO2 Measurements in Breast Cancer

“…Metalltrokar unter Anoxie; 1 000 Messwerte pro "box whisker plot" für eine Messsonde; 5 000 Messwerte für die zusammengefassten Ergebnisse an einem Histographen (p = 0,9; 50% der Messwerte liegen innerhalb der "box"; Markierung in der "box" entspricht dem Median, die "whiskers" markieren das Maximum und Minimum der Messwerte [25]). …”

“…Figure 4. Results of five different pO 2 measurement probes for two histographs A and B under anoxic conditions and pooled data; median of -0.9 mmHg ± 0.64 for histograph A and 0.3 mmHg ± 0.76 for histograph B (p < 0.01; 50% of the values within the box; the mark in the box indicates the median, the whiskers mark the maximum and minimum of the values [25]). …”

“…unter Anoxie und zusammengefasste Daten; Median von -0,9 mmHg ± 0,64 für Histograph A und 0,3 mmHg ± 0,76 für Histograph B (p < 0,01; 50% der Messwerte liegen innerhalb der "box"; Markierung in der "box" entspricht dem Median, die "whiskers" markieren das Maximum und Minimum der Messwerte [25] …”

“…This might be overcome by targeted intervention to improve oxygenation [8,33,34] or by use of hypoxic cell sensitizers [25]. In breast cancer, hypoxia-induced pathways have been found to lead to a dedifferentiated, aggressive phenotype [10,11,15,19,28,29] and impaired response to radiotherapy [13,19,27,28], chemo-and hormonal therapy [6,7,11,15,28,29].…”

“…Results for five different pO 2 measurement probes, measured without (-) and with (+) the metal trocar under anoxic conditions; 1,000 values per box-whisker plot for each needle electrode; 5,000 values per box-whisker plot for pooled results (p = 0.9; 50% of the values within the box; the mark in the box indicates the median, the whiskers mark the maximum and minimum of the values[25]). …”