Early phase trial of intracystic injection of large surface area microparticle paclitaxel for treatment of mucinous pancreatic cysts

Autor: Mohamed Othman, Kalpesh Patel, Somashekar G. Krishna, Antonio Mendoza-Ladd, Shelagh Verco, Wasif Abidi, James Verco, Alison Wendt, Gere diZerega
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Endoscopy International Open, Vol 10, Iss 12, Pp E1517-E1525 (2022)
Druh dokumentu: article
ISSN: 2364-3722
2196-9736
DOI: 10.1055/a-1949-7730
Popis: Background and study aims Mucinous pancreatic cystic lesions (PCLs) have the potential for malignant transformation, for which the only accepted curative modality is surgery. A novel intracystic therapy with large surface area microparticle paclitaxel (LSAM-PTX) may treat PCLs without local or systemic toxicities. Safety and preliminary efficacy of LSAM-PTX for the treatment of PCLs administered by endoscopic ultrasound-guided fine-needle injection (EUS-FNI) was evaluated. Patients and methods Ten subjects with confirmed PCLs (size > 1.5 cm) received intracystic LSAM-PTX via EUS-FNI at volumes equal to those aspirated from the cyst in sequential cohorts at 6, 10, and 15 mg/mL in a standard “3 + 3” dose-escalation protocol. The highest dose with acceptable safety and tolerability was taken into the confirmatory phase where nine additional subjects received two injections of LSAM-PTX 12 weeks apart. Subjects were followed for 6 months after initial LSAM-PTX treatment for endpoints including: adverse events (AEs), tolerability, pharmacokinetic analysis of systemic paclitaxel drug levels, and change in cyst volume. Results Nineteen subjects completed the study. No dose-limiting toxicities, treatment-related serious AEs, or clinically significant laboratory changes were reported. Systemic paclitaxel concentrations did not exceed 3.5 ng/mL at any timepoint measured and fell below 1 ng/mL by Week 2, supporting the lack of systemic toxicity. By Week 24 a cyst volume reduction (10–78 %) was seen in 70.6 % of subjects. Conclusions Intracystic injection of LSAM-PTX into mucinous PCLs resulted in no significant AEs, a lack of systemic absorption, and resulted in reduction of cyst volume over a 6 month period.
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