Implants for Cost-Effective and Accessible Treatment of Gynecologic and Gastrointestinal Cancer Metastasis by Local and Sustained Low-Dose Chemotherapy

Abstract

46 Gynecologic and gastrointestinal malignancies are two of the most prevalent cancer types in low and middle- income countries (LMICs), affecting more than 2 million individuals and killing more than 1 million patients annually. These malignancies at an advanced stage metastasize locally but extensively; this spread is a primary cause of morbidity and mortality, affecting 60-80% of patients in LMICs. Localized chemotherapy can benefit survival of patients with such metastases. Localized chemotherapy is, however, essentially unattainable in resource-limited settings, even though many chemotherapy agents are on the WHO list of essential medicines and are currently off patent. This is because of the high cost of, and frequent hospitalizations required under, the current regimen, as well as the morbidity of bolus dosing. Continuous, low-dose chemotherapy via a locally implanted device can address these adoption barriers. Previous attempts to create implants for localized chemotherapy delivery have been hindered by poorly controlled drug release and inhibiting form factors. This work explores the development of a nonresorbable and laparoscopically deployable implant to administer continuous low-dose chemotherapy. The feasibility of chemotherapy using the proposed implant in LMICs is assessed using physician interviews and literature reviews. Tissue-like silicone elastomers are used to create a matrix-type drug delivery implant that minimizes soft tissue irritation and risk of rupture while allowing laparoscopic manipulation. The synthesis and drug release profile of the silicone-based matrix are characterized for small hydrophilic active agents. Configurations allowing implant deployment through laparoscopic instruments are explored. Proof-of-concept controlled release of a hydrophilic small molecule from a lipophilic, tissue-like silicone elastomer that can be scaled to human form factors is thus established. Localized, low-dose chemotherapy delivered via a fully implantable device holds promise to dramatically reduce the cost and resources necessary for treating advanced-stage gynecologic and gastrointestinal malignancies in LMICs, improving cancer patient outcomes in resource-limited settings. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST: Aikaterini Mantzavinou No relationship to disclose Michael J. Cima Leadership: T2 Biosystems, MicroChips Biotechnologies, Taris BioMedical Stock or Other Ownership: T2 Biosystems, MicroChips Biotechnologies, Taris BioMedical Research Funding: Pfizer Patents, Royalties, Other Intellectual Property: Too many to describe (over 50 patents) Expert Testimony: Apotex Laura Melanie Tanenbaum Patents, Royalties, Other Intellectual Property: System and Method for Sterile Sheathing of a Medical Probe