Combining Vascular Targeting Agents with Radiation: An Effective Anti-Tumor Treatment but Associated with Radiation-Induced Systemic Toxicity
This study investigated the effect of combining radiation with an angiogenesis inhibitor and vascular disrupting agent on tumor response and systemic toxicity. CDF1 mice with 200 mm<sup>3</sup> foot implanted C3H mammary carcinomas were treated with TNP-470 (100 mg/kg every second day fo...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-10-01
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| Series: | Radiation |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2673-592X/4/4/24 |
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| Summary: | This study investigated the effect of combining radiation with an angiogenesis inhibitor and vascular disrupting agent on tumor response and systemic toxicity. CDF1 mice with 200 mm<sup>3</sup> foot implanted C3H mammary carcinomas were treated with TNP-470 (100 mg/kg every second day for 2 weeks; s.c.) and combretastatin A-4 phosphate (CA4P; 1 × 250 mg/kg, i.p.). Radiation (230-kV X-rays) was locally administered to tumors of restrained non-anesthetized mice. Response was tumor growth delay and change in mouse body weight. Radiation induced changes in serum levels of 10 cytokines up to 72-h after irradiation were measured using a Luminex assay. The results showed that TNP-470 (100 mg/kg × 7) or CA4P (250 mg/kg × 1) significantly (Student’s <i>t</i>-test; <i>p</i> < 0.05) inhibited tumor growth; the greatest effect when these two drugs were combined. TNP-470 and CA4P, alone or together, also significantly enhanced tumor response to radiation. No systemic toxicity occurred with drugs administered alone or in combination, but toxicity was observed when TNP-470 was combined with radiation. Serum cytokine levels only showed a significant transient increase in IL-6 1-h after irradiating. In conclusion, combining different acting vascular targeting agents with radiation increased anti-tumor activity. However, this benefit may sometimes be associated with a radiation-induced inflammatory response increasing systemic toxicity. |
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| ISSN: | 2673-592X |