GNAS mutations as prognostic biomarker in patients with relapsed peritoneal pseudomyxoma receiving metronomic capecitabine and bevacizumab: a clinical and translational study
| Autor: | Federica Perrone, Ilaria Bossi, Marcello Deraco, Adele Busico, Shigeki Kusamura, Massimo Milione, Marta Caporale, Rosa Berenato, Alessia Mennitto, Maria Di Bartolomeo, Filippo Pietrantonio, Annunziata Gloghini, Luigi Mariani, Elena Tamborini, Claudia Maggi, Giulio Settanni, Filippo de Braud, Dario Baratti, Monica Niger, Pietro Francesco Bagnoli |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Oncology Kaplan-Meier Estimate Metronomic capecitabine Translational Research Biomedical 0302 clinical medicine GTP-Binding Protein alpha Subunits Gs Clinical endpoint Pseudomyxoma peritonei Peritoneal Neoplasms Medicine(all) biology General Medicine Middle Aged Prognosis Bevacizumab Treatment Outcome 030220 oncology & carcinogenesis Female Hyperthermic intraperitoneal chemotherapy medicine.drug medicine.medical_specialty Appendiceal cancer Disease-Free Survival General Biochemistry Genetics and Molecular Biology Capecitabine GNAS 03 medical and health sciences Median follow-up Internal medicine Biomarkers Tumor Chromogranins medicine GNAS complex locus Humans Aged Biochemistry Genetics and Molecular Biology(all) Genome Human business.industry Research Pseudomyxoma Peritonei medicine.disease 030104 developmental biology Administration Metronomic Mutation Next-generation sequencing biology.protein Peritoneal pseudomyxoma Neoplasm Recurrence Local business Progressive disease |
| Zdroj: | Journal of Translational Medicine |
| ISSN: | 1479-5876 |
| Popis: | Background There is lack of evidence about systemic treatment of pseudomyxoma peritonei (PMP) relapsing after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. There is also lack of biomarkers able to predict outcomes beyond known clinical and pathological prognostic features. Methods Fifteen patients with relapsed PMP and progressive disease within the last 6 months were included and received metronomic capecitabine (625 mg/mq/day b.i.d.) and bevacizumab (7.5 mg/Kg three-weekly) until progressive disease/unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Ion Torrent® next generation sequencing technology (Hot-spot Cancer Panel) was used to characterize molecular features. Results At a median follow up of 12 months, median PFS was 8.2 months and 1-year overall survival was 91 %. Partial responses were observed in 20 % of cases, but a significant reduction of tumor markers in up to 79 %. Treatment was very well tolerated without no new safety signals. All tumor samples except one had KRAS mutations. Patients with GNAS mutations had a significantly shorter median PFS as compared to GNAS wild-type ones (5.3 months vs. not reached; p |
| Databáze: | OpenAIRE |
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