Preclinical studies of the Chinese Herbal Medicine formulation PHY906 (KD018) as a potential adjunct to radiation therapy

摘要

Objective: Abdominal and pelvic radiotherapy is limited by the radiosensitivity of the small and large intestine. PHY906 (KD018), a state-of-the-art, well defined adaptation of a traditional Chinese medicine, decreased intestinal injury from chemotherapy in preclinical studies and is in clinical trials with chemotherapy. This project assessed whether PHY906 would also reduce intestinal injury from abdominal irradiation in mice. Materials and methods: BALB/c mice received whole-abdomen irradiation (2 Gy/day) ± PHY906 by oral gavage twice daily for 4 days. Intestinal injury was assayed by physiological observations and histological studies. Effects of PHY906 on EMT6 mouse mammary tumors were assayed in tumor growth studies. Results: PHY906 decreased toxicity from fractionated abdominal irradiation. Radiation alone produced marked blunting and loss of villi, crypt hyperplasia and irregular crypt morphology, which were reduced by PHY906. The radiation-induced reduction in viable crypt numbers was also mitigated by PHY906. PHY906 did not alter radiation-induced weight loss, but resulted in more rapid recovery. PHY906 did not alter tumor growth, local invasion or metastatic spread and did not protect tumors from growth delays produced by single-dose or fractionated irradiation. Conclusion: In this mouse model, PHY906 (KD018) decreased the toxicity of abdominal irradiation without protecting tumors and thereby increased the therapeutic ratio.