Abstract
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.
