Document Detail

Bevacizumab plus fotemustine as first-line treatment in metastatic melanoma patients: clinical activity and modulation of angiogenesis and lymphangiogenesis factors.
MedLine Citation:
PMID:  21030496     Owner:  NLM     Status:  MEDLINE    
PURPOSE: To assess the clinical and biological activity of the association of bevacizumab and fotemustine as first-line treatment in advanced melanoma patients.
EXPERIMENTAL DESIGN: Previously untreated, metastatic melanoma patients (n = 20) received bevacizumab (at 15 mg/kg every 3 weeks) and fotemustine (100 mg/m² by intravenous administration on days 1, 8, and 15, repeated after 4 weeks) in a multicenter, single-arm, open-label, phase II study. Primary endpoint was the best overall response rate; other endpoints were toxicity, time to progression (TTP), and overall survival (OS). Serum cytokines, angiogenesis, and lymphangiogenesis factors were monitored by multiplex arrays and by in vitro angiogenesis assays. Effects of fotemustine on melanoma cells, in vitro, on vascular endothelial growth factor (VEGF)-C release and apoptosis were assessed by ELISA and flow cytometry, respectively.
RESULTS: One complete response, 2 partial responses (PR), and 10 patients with stable disease were observed. TTP and OS were 8.3 and 20.5 months, respectively. Fourteen patients experienced adverse events of toxicity grade 3-4. Serum VEGF-A levels in evaluated patients (n = 15) and overall serum proangiogenic activity were significantly inhibited. A significant reduction in VEGF-C levels was found in several post-versus pretherapy serum samples. In vitro, fotemustine inhibited VEGF-C release by melanoma cells without inducing significant cell death. Serum levels of interleukin (IL)-10 and IL-12p70 showed the highest levels in sera of PR patients, compared with patients with stable or progressive disease whereas IL-23 showed the opposite pattern.
CONCLUSIONS: The combination of bevacizumab plus fotemustine has clinical activity in advanced melanoma and promotes systemic modulation of angiogenesis and lymphangiogenesis factors.
Michele Del Vecchio; Roberta Mortarini; Stefania Canova; Lorenza Di Guardo; Nicola Pimpinelli; Mario R Sertoli; Davide Bedognetti; Paola Queirolo; Paola Morosini; Tania Perrone; Emilio Bajetta; Andrea Anichini
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Publication Detail:
Type:  Clinical Trial, Phase II; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't     Date:  2010-10-28
Journal Detail:
Title:  Clinical cancer research : an official journal of the American Association for Cancer Research     Volume:  16     ISSN:  1078-0432     ISO Abbreviation:  Clin. Cancer Res.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-08     Completed Date:  2011-03-31     Revised Date:  2013-05-27    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5862-72     Citation Subset:  IM    
Copyright Information:
©2010 AACR.
Unit of Medical Oncology 2, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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MeSH Terms
Angiogenic Proteins / blood*,  metabolism
Antibodies, Monoclonal / administration & dosage*,  adverse effects
Antibodies, Monoclonal, Humanized
Antineoplastic Combined Chemotherapy Protocols / adverse effects,  therapeutic use*
Cells, Cultured
Lymphangiogenesis* / physiology
Melanoma / blood,  drug therapy*,  metabolism,  pathology
Middle Aged
Neoadjuvant Therapy
Nitrosourea Compounds / administration & dosage*,  adverse effects
Organophosphorus Compounds / administration & dosage*,  adverse effects
Skin Neoplasms / blood,  drug therapy*,  metabolism,  pathology
Treatment Outcome
Tumor Markers, Biological / blood,  metabolism
Vascular Endothelial Growth Factor A / blood,  metabolism
Vascular Endothelial Growth Factor C / blood,  metabolism
Young Adult
Reg. No./Substance:
0/Angiogenic Proteins; 0/Antibodies, Monoclonal; 0/Antibodies, Monoclonal, Humanized; 0/Nitrosourea Compounds; 0/Organophosphorus Compounds; 0/Tumor Markers, Biological; 0/VEGFA protein, human; 0/Vascular Endothelial Growth Factor A; 0/Vascular Endothelial Growth Factor C; 2S9ZZM9Q9V/bevacizumab; 92118-27-9/fotemustine
Erratum In:
Clin Cancer Res. 2011 Feb 1;17(3):630

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