Supported by

IndoUS Science and Technology Fund

Principal Investigators:

PROJECT SUMMARY

Cancer is a leading cause of death in developed as well as in developing countries. Among various deadly cancers, the incidence of head and neck cancer (HNC) in the world is on rise. Among HNC, oral cavity cancer is the second most common in India and accounts for 86% of the world’s oral cancer cases (National Institute of Public Health in February 2011). The appearance of 800,000 – 900,000 new cases every year poses an alarming threat worldwide. Modern modalities to treat HNC are radiation, chemotherapy, surgery, antibody-blocking therapy, or a combination of these therapies. In spite of technological developments, the available therapies for HNC suffer significant limitations. The presence of important organs such as carotid artery, eye, and brain in head and neck area hinders surgical resection. At the same time, the high failure rate and toxicity of radiotherapy limits its utility.

Docetaxel is a leading FDA approved chemotherapeutic for HNC. Leading clinicians at Dana Farber Cancer Institute and others have shown the efficacy of combining chemo- and radiation therapy, particularly taxanes like docetaxel. [1,2] However docetaxel which is administered systemically leads to severe systemic toxicity such as neutropenia. Furthermore the current systemic administration is highly inefficient with poor tumor accumulation and is bio-active only for a day or so. Accordingly there is a tremendous need for an approach that is highly efficient in delivery and the same time minimizes toxicity.

Here we propose to test an innovative sustained local drug release nanoplatform for HNC capable of locally radio-sensitizing the specific HNC malignant site and minimizing systemic toxicity and reducing the radiation dosage. The proposed design involves using poly (lactic-co-glycolic acid) (PLGA) nanoparticles loaded with a model radiosensitizing drug Docetaxel (DTX) which will be administered intra-tumorally to provide localized in-situ delivery of the sensitizer to the tumor site. This will avoid the toxicity associated with current systemic delivery of radiosensitizers. The nanoplatform will improve the therapeutic ratio of radiation therapy without introducing additional patient interventions. This innovative approach is expected to results in new modalities in localized chemotherapy (LCT) and localized chemo-radiation therapy (LCRT).