Grant R21CA149956


DESCRIPTION (provided by applicant): Cancer is a group of diseases characterized by uncontrolled growth and spread of abnormal cells. Over one million people get cancer each year. Approximately one out of every two American men and one out of every three American women will have some type of cancer at some point during their lifetime. Cisplatin is one of the most commonly used drugs in chemotherapy for cancers. However, severe adverse events resulting from chemotherapies, mainly nausea and vomiting may be much more distressing to a patient than future concerns of life expectancy. In fact, some patients choose to discontinue potentially curative therapy because of severe Cisplatin-induced nausea and vomiting. Antiemetic agents are the most common intervention in the management of chemotherapy-induced nausea and vomiting in cancer patients. The basis for antiemetic therapy is the neurochemical control of vomiting. However, currently, there are no satisfactory therapies for treating chemotherapy-induced emesis, especially delayed emesis. Acupuncture or electroacupuncture (EA) has been applied for treating chemotherapy-induced nausea and vomiting. A recent meta-analysis has indicated that electrical stimulation of the acupoint via inserted needles is effective in reducing acute vomiting when applied in combination with the anti-emetic medications. The long-term aim of this project is to develop an effective EA method to treat patients with chemotherapy-induced nausea and vomiting. In this project, we propose an innovative method of chronic EA delivered via chronically implanted electrodes at acupoints and an implantable pulse generator placed underneath the abdominal skin. With this new method, EA can be delivered on-demand conveniently by the patient or continuously. Systematic studies will be performed in this project to optimize the methodology of EA (best EA locations and optimal stimulation parameters). The hypothesis that chronic EA is effective in treating chemotherapy-induced emesis will be tested in a rodent model using pica (consumption of clay). Mechanistic studies will also be performed to test the hypotheses that EA is mediated via the vagal neuronal pathway and involves central neurotransmitters, dopamine and serotonin. The feasibility, safety and efficacy of chronic EA in controlling acute and delayed emesis induced by long-term cisplatin will also be investigated. A competitive team has been established, including experts in Traditional Chinese Medicine, gastrointestinal electrical stimulation, physiology of the central nervous system and medical device. PUBLIC HEALTH RELEVANCE: Chemotherapy-induced emesis is one of major problems in the treatment of patients with cancer and occurs in more than 90% of cases with certain medications, such as Cisplatin. With the recent advancement of anti-emetic medications, acute emesis is better controlled;however, delayed emesis remains a big challenge. A novel method of chronic electroacupuncture using implantable electrodes and stimulator is proposed in this project for the treatment of chemotherapy-induced emesis. Preliminary data supports this novel concept and experiments are designed to test the feasibility of the proposed method.