Response of Locally Advanced Pancreatic Cancer to Intratumoral Injection of Large Surface Area Microparticle Paclitaxel: Initial Report of Safety and Clinical Outcome

• Published in: Pancreas Vol. 52; no. 3; p. e179
• Main Authors: Sharma, Neil R, Lo, Simon K, Hendifar, Andrew, Othman, Mohamed O, Patel, Kalpesh, Mendoza-Ladd, Antonio, Verco, Shelagh, Maulhardt, Holly A, Verco, James, Wendt, Alison, Marin, Alyson, Schmidt, Christian Max, diZerega, Gere
• Format: Journal Article
• Language: English
• Published: United States 01.03.2023
• Subjects: Humans; Injections, Intralesional; Neoadjuvant Therapy - methods; Paclitaxel; Pancreatic Hormones; Pancreatic Neoplasms - pathology
• ISSN: 1536-4828
• DOI: 10.1097/MPA.0000000000002236

Large surface area microparticle paclitaxel (LSAM-PTX) provides an intratumoral (IT) chemotherapeutic depot. Safety, tolerability, and tumor response to IT LSAM-PTX delivered by endoscopic ultrasound-fine needle injection were evaluated in subjects with unresectable locally advanced pancreatic cancer (LAPC). Ten subjects treated in a dose escalation phase and 22 additional subjects receiving 2 injections, 4 weeks apart, of 15 mg/mL LSAM-PTX were followed for 12 months. Paclitaxel pharmacokinetics were evaluated, imaging at 3 and 6 months determined tumor response, and multiplex immunofluorescence was conducted to characterize local immune response. Most treatment-emergent adverse events were attributed to LAPC. Plasma paclitaxel levels were negligible. Eight subjects' tumors became resectable after IT LSAM-PTX, and 5 of 6 (83%) were resected with R0. Multiplex immunofluorescence of resected tumors demonstrated increased T cells, natural killer cells, and macrophages and decreased myeloid-derived suppressor cells. Six-month disease control rate was 94%, and median overall survival was 19.7 months in the 2-injection subjects. For nonresected and resected groups, overall survival times were 18.9 and 35.2 months, respectively. Neoadjuvant IT LSAM-PTX, in combination with SOC, was well tolerated and may provide benefits to LAPC patients, evidenced by enhanced immune response, improved disease control rate, restaging leading to surgery, and extended survival.