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A phase II open label trial evaluating safety and efficacy of a telomerase peptide vaccination in patients with advanced hepatocellular carcinoma

BACKGROUND: The sole effective option for patients with advanced HCC is sorafenib and there is an urgent need to develop new therapeutic approaches. Immunotherapy is a promising option that deserves major investigation. In this open label, single arm clinical trial, we analyzed the effect of a low d...

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Detalles Bibliográficos
Autores principales: Greten, Tim F, Forner, Alejandro, Korangy, Firouzeh, N'Kontchou, Gisele, Barget, Nathalie, Ayuso, Carmen, Ormandy, Lars A, Manns, Michael P, Beaugrand, Michel, Bruix, Jordi
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882353/
https://www.ncbi.nlm.nih.gov/pubmed/20478057
http://dx.doi.org/10.1186/1471-2407-10-209
Descripción
Sumario:BACKGROUND: The sole effective option for patients with advanced HCC is sorafenib and there is an urgent need to develop new therapeutic approaches. Immunotherapy is a promising option that deserves major investigation. In this open label, single arm clinical trial, we analyzed the effect of a low dose cyclophosphamide treatment in combination with a telomerase peptide (GV1001) vaccination in patients with advanced HCC. METHODS: 40 patients with advanced HCC were treated with 300 mg/m(2 )cyclophosphamide on day -3 followed by GM-CSF + GV1001 vaccinations on days 1, 3, 5, 8, 15, 22, 36 followed by 4-weekly injections. Primary endpoint of this phase II trial was tumor response; secondary endpoints evaluated were TTP, TTSP, PFS, OS, safety and immune responses. RESULTS: None of the patients had a complete or partial response to treatment, 17 patients (45.9%) demonstrated a stable disease six months after initiation of treatment. The median TTP was 57.0 days; the median TTSP was estimated to be 358.0 days. Cyclophosphamide, GV1001 and GM-CSF treatment were well tolerated and most adverse events, which were of grade 1 or 2, were generally related to the injection procedure and injection site reactions. GV1001 treatment resulted in a decrease in CD4(+)CD25(+)Foxp3(+ )regulatory T cells; however, no GV1001 specific immune responses were detected after vaccination. CONCLUSIONS: Low dose cyclophosphamide treatment followed by GV1001 vaccinations did not show antitumor efficacy as per tumor response and time to progression. Further studies are needed to analyze the effect of a combined chemo-immunotherapy to treat patients with HCC. TRIAL REGISTRATION: NCT00444782