Tolerability and safety of EUS-injected adenovirus-mediated double-suicide gene therapy with chemotherapy in locally advanced pancreatic cancer: a phase 1 trial.
Gastrointest Endosc
; 92(5): 1044-1052.e1, 2020 11.
Article
en En
| MEDLINE
| ID: mdl-32084409
ABSTRACT
BACKGROUND AND AIMS:
Locally advanced pancreatic cancer (LAPC) is challenging. Here, we aimed to evaluate the tolerability and safety of Ad5-yCD/mutTK(SR39)rep-ADP (Ad5-DS), a replication-competent adenovirus-mediated double-suicide gene therapy in combination with gemcitabine in patients with LAPC.METHODS:
Patients with newly diagnosed LAPC were enrolled in this single-center, open-label, 3 + 3 dose-escalation phase 1 trial. Ad5-DS was injected into the pancreatic mass with EUS-guided fine needles combined with oral 5-fluorocytosine and valganciclovir, and a standard dose of intravenous gemcitabine. The doses of Ad5-DS in cohorts 1 to 3 were 1 × 1011, 3 × 1011, and 1 × 1012 viral particles (vp)/mL, respectively. Patients were observed for dose-limiting toxicity (DLT) for 8 weeks after Ad5-DS injection. Toxicity within 12 weeks, tumor response in 12 weeks, disease progression in 6.5 months, and detection of adenoviral DNA particles in 8 weeks were also assessed.RESULTS:
Among the 11 enrolled patients, 9 completed the evaluation period and 2 withdrew their consent. No DLT was reported; thus, the maximum tolerated dose was not reached. No additional toxicity was reported in 9 to 12 weeks. One patient showed a partial response and 8 showed stable disease at 12 weeks. Two patients showed disease progression at 6.5 months (median progression-free survival, 11.4 months). At 8 weeks, serum adenoviral DNA particles were detected in 4 patients (median, 55 days).CONCLUSION:
A combination of intratumoral Ad5-DS and gemcitabine is safe and well tolerated in patients with LAPC. This warrants further investigation in a larger clinical trial. (Clinical trial registration number NCT02894944.).
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Pancreáticas
/
Terapia Genética
/
Adenoviridae
Límite:
Humans
Idioma:
En
Revista:
Gastrointest Endosc
Año:
2020
Tipo del documento:
Article