Prevention of Peripheral Neuropathy Side Effect in Chemotherapy Treatment of Lung Cancer
Abstract
This proposal is to test the use of low intensity ultrasonic/ultrasound treatment to counter taxane chemotherapy-induced peripheral neuropathy (a major side effect of the cancer treatment), based on our initial laboratory discovery. The removal of the dose limiting side effect will enable the optimal use of taxane to treat primary and recurrent metastatic lung cancer. Potentially, a higher dosage of taxanes can be used to counter the problem of drug resistance. The ultrasound treatment will also improve quality of life for cancer patients. Taxanes (Taxol/paclitaxel, Taxotere/docetaxel, Jevtana/cabazitaxel) are a key group of drugs in the current treatment of several major solid tumors, including both small cell and non-small cell lung cancer, used as a single agent or in combination with additional drugs. Currently, Taxane/platinum combinations still remain the foundation in the management of advanced or metastatic non-small cell lung cancer. Docetaxel and paclitaxel as single agents are also effective in the second-line setting in advanced/metastatic lung cancer. Although generally taxanes are highly effective with tolerable side effects, sensory neuropathy, presenting as numbness and pain of feet and hands, is often the dose-limiting toxicity of the agents. Currently, cooling gloves and socks are used to reduce drug exposure during chemotherapy with uncertain or limited success, but no satisfactory methods are available to prevent or reverse this side effect of taxanes. We have made a surprising discovery that low-intensity ultrasound treatment can effectively and completely neutralize the cytotoxic effect of taxanes on cells in culture. To apply this discovery, our proposed study is to develop the use of ultrasound to prevent the side effect (sensory neuron toxicity) of taxanes in treating patients. This approach may be especially attractive as ultrasound treatment can be targeted and limited to local regions, such as the hands and feet, instead of systematically affecting the whole body. Thus, our ultrasound treatment may overcome taxane toxicity only in hands and feet to prevent peripheral neuropathy without affecting the efficacy of the taxane drug to kill cancer cells elsewhere. The biological basis is that taxane kills cancer cells and causes neuronal toxicity by stabilizing cellular microtubule bundles, and local ultrasound shock waves break the microtubule bundles so to eliminate the effect of the drug in the targeted neuronal cells without affecting the killing of cancer cells. In this research proposal, we plan to understand further the science underlying our discovery and to explore questions and gain information to plan a procedure for a practical clinical intervention. The work includes the further study of ultrasound effects on primary neuronal cells in culture, in animal models, and the evaluation of suitable ultrasound devices for optimal efficacy. Our goal includes the formulation of a clinical protocol and consideration of the details of a clinical trial based on the study. The goal is that by the end of this 1-year laboratory study, or even before, we will be able to immediately carry out a clinical trial to use low-intensity ultrasound to prevent taxane side effect in chemotherapy treatment of lung cancer patients. This research project will likely impact on common chemotherapy using taxane: removing the dose-limiting side effect of the therapy and enabling effective treatment of patients with primary and recurrent metastatic breast cancer. The overcoming of the side effect will enable an increased dose or prolong treatment with taxanes, either in the initial treatment or salvage therapy, which will surely extend the survival and improve the quality of life of lung cancer patients. The results of the proposed study may be able to guide the costumed design and manufacture of an ultrasound device that is optimal in the treatment of taxane-induced peripheral neuropathy. If the pr
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310049
Entities
People
- Xiangxi Xu
Organizations
- United States Army
- University of Miami