Phase II Study of Gemcitabine Plus Sirolimus in Previously Treated Patients with Advanced Soft-Tissue Sarcoma: a Spanish Group for Research on Sarcomas (GEIS) Study.
Target Oncol
; 13(1): 81-87, 2018 02.
Article
em En
| MEDLINE
| ID: mdl-29177953
ABSTRACT
BACKGROUND:
Gemcitabine plus sirolimus enhances apoptosis in vitro and increases anti-tumor efficacy in vivo in soft-tissue sarcoma (STS) models.OBJECTIVE:
The objective of this study was to evaluate the activity and toxicity of the combination of gemcitabine plus sirolimus in patients with STS after failure of standard chemotherapy. PATIENTS ANDMETHODS:
Advanced STS patients, previously treated with doxorubicin and/or ifosfamide, were included in this single-arm phase II study. Patients received gemcitabine 800 mg/m2 intravenously (iv) at 10 mg/m2/min on days 1 and 8 every 3 weeks plus sirolimus 5 mg daily orally (po). After enrolment of the first 12 patients, the study protocol was amended due to toxicity and the starting dose of sirolimus was reduced to 3 mg daily po. Archival tumor samples were analyzed for extracellular signal-regulated kinase 1 and 2 (ERK1/2) expression and correlated with outcome. The primary endpoint was progression-free rate (PFR) at 3 months.RESULTS:
From May 2012 to May 2013, 28 patients were enrolled at eight centers. PFR at 3 and 6 months was 44% and 20%, respectively, with 12 patients being free of progression at 3 months. Median progression-free survival (PFS) was 1.85 months (95% confidence interval [CI] 0.73-2.97) and median overall survival (OS) was 9.2 months (95% CI 5.8-12.5). No responses were observed. The most common grade 3-4 hematologic toxicities were neutropenia (48%) and leukopenia (41%) and the most frequent grade 3 non-hematologic toxicities were infection (18.5%), transaminitis (15%), fatigue (11%), and pneumonitis (11%). ERK1/2 expression was significantly correlated with PFS (p = 0.026).CONCLUSIONS:
The combination of gemcitabine and sirolimus is an active treatment in STS. Further investigation is warranted. ClinicalTrials.gov identifier NCT01684449.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sarcoma
/
Sirolimo
/
Desoxicitidina
/
Antimetabólitos Antineoplásicos
Tipo de estudo:
Guideline
/
Prognostic_studies
Limite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Target Oncol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Espanha