RNAi therapy targeting KRAS in combination with chemotherapy for locally advanced pancreatic cancer patients.
Oncotarget
; 6(27): 24560-70, 2015 Sep 15.
Article
en En
| MEDLINE
| ID: mdl-26009994
ABSTRACT
PURPOSE:
The miniature biodegradable implant siG12D-LODER™ was inserted into a tumor and released a siRNA drug against KRAS(G12D) along four months. This novel siRNA based drug was studied, in combination with chemotherapy, as targeted therapy for Locally Advanced Pancreatic Cancer (LAPC).METHODS:
An open-label Phase 1/2a study in the first-line setting of patients with non-operable LAPC was initiated. In this study patients were assigned to receive a single dose of siG12D-LODERs, in three escalating dose cohorts (0.025mg, 0.75mg and 3.0mg). Gemcitabine was given on a weekly basis, following the siG12D-LODERTM insertion, until disease progression. The recommended dose was further examined with modified FOLFIRINOX. The follow up period was eight weeks and survival until death.RESULTS:
Fifteen patients with LAPC were enrolled. Among the 15 treated patients, the most frequent adverse events observed were grade 1or 2 in severity (89%); five patients experienced serious adverse events (SAEs). In 12 patients analyzed by CT scans, none showed tumor progression, the majority (10/12) demonstrated stable disease and two showed partial response. Decrease in tumor marker CA19-9 was observed in 70% (7/10) of patients. Median overall survival was 15.12 months; 18 month survival was 38.5%.CONCLUSIONS:
The combination of siG12D-LODER™ and chemotherapy is well tolerated, safe and demonstrated a potential efficacy in patients with LAPC. NCT01188785.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Pancreáticas
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Proteínas Proto-Oncogénicas p21(ras)
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Carcinoma Ductal Pancreático
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ARN Interferente Pequeño
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Implantes de Medicamentos
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Terapia Molecular Dirigida
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Tratamiento con ARN de Interferencia
Tipo de estudio:
Clinical_trials
Límite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Oncotarget
Año:
2015
Tipo del documento:
Article
País de afiliación:
Israel