Therapeutic potential of using the vascular disrupting agent OXi4503 to enhance mild temperature thermoradiation

Figures & data

Figure 1. The effect of OXi4503 (50 mg/kg) and mild temperature hyperthermia (41.5 °C, 60 min) on the radiation response of a C3H mammary carcinoma. (A) Radiation dose response curves for local tumour control in tumours treated with radiation alone (△), OXi4503 injected 1.5 h before irradiating (▴), radiation administered in the middle of heating (○), or the combination of OXi4503, radiation and heat (•). Points are for an average of 10 mice with the lines drawn following logit analysis. (B) The TCD₅₀ doses are a function of time relative to irradiation, and are taken from the curves shown in (A) and for other similar dose–response curves. Results are for radiation alone (

), OXi4503 injected 1.5 h before irradiating (▴), radiation and heat (○), and OXi4503, radiation and heat (•). Radiation was administered at time zero. Points involving radiation and heat are shown at the middle of the 1-h heating period. Errors are 95%CI.

Figure 2. The effect of OXi4503 (50 mg/kg) and mild temperature hyperthermia (41.5 °C, 60 min) on the radiation response of normal foot skin. (A) Radiation dose response curves for moist desquamation in skin treated with radiation alone (△), OXi4503 injected 1.5 h before irradiating (▴), radiation administered in the middle of heating (○), or the combination of OXi4503, radiation and heat (•). Points are for an average of seven mice with the lines drawn following logit analysis. (B) The MDD₅₀ doses are a function of time relative to irradiation, and are taken from the curves shown in (A) and for other similar dose–response curves. Results are for radiation alone (

), OXi4503 injected 1.5 h before irradiating (▴), radiation and heat (○), and OXi4503, radiation and heat (•). Radiation was administered at time zero. Points involving radiation and heat are shown at the middle of the 1-h heating period. Errors are 95%CI.

Table 1. Comparison of the effects of OXi4503 and/or mild temperature hyperthermia on the radiation response of the C3H mammary carcinoma or normal foot skin.

	Enhancement ratio^2
Treatment^1	Tumour	Skin	Therapeutic gain factor^3
Radiation during heat	1.64* (1.53–1.76)	2.17* (2.00–2.34)	0.76** (0.60–0.91)
Radiation 1 h before heat	1.17* (1.10–1.25)	1.18* (1.10–1.27)	0.99 (0.88–1.10)
Radiation 4 h before heat	1.11* (1.05–1.18)	0.98 (0.89–1.07)	1.13** (1.01–1.26)
OXi4503 1.5 h before radiation	1.12* (1.06–1.19)	1.05* (1.00–1.10)	1.07 (0.98–1.15)
OXi4503 1.5 h before radiation during heat	1.70* (1.55–1.87)	2.47* (2.26–2.69)	0.69** (0.50–0.88)
OXi4503 1.5 h before radiation 1 h before heat	1.54* (1.39–1.69)	1.24* (1.19–1.28)	1.24** (1.05–1.44)
OXi4503 1.5 h before radiation 4 h before heat	1.52* (1.38–1.67)	1.06* (1.01–1.11)	1.43** (1.22–1.65)

¹Treatments: Radiation, mild temperature hyperthermia of 41.5 °C for 60 min (Heat), or 50 mg/kg OXi4503.

²Enhancement ratios were calculated from the data of Figures 1 and 2 and are the ratios of the TCD₅₀ (tumour) and MDD₅₀ (skin) values for radiation alone compared to the other treatments; errors are 95%CI. *Values significantly different from radiation alone.

³Therapeutic gain factors were calculated by comparing the enhancement ratios for tumours to those of skin; errors are 95%CI. **Values where the tumour and skin values were significantly different.