Bevacizumab plus fotemustine as first-line treatment in metastatic melanoma patients

Clinical activity and 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

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)5862-5872
Number of pages11
JournalClinical Cancer Research
Volume16
Issue number23
DOIs
Publication statusPublished - 1 Dec 2010
Externally publishedYes

Fingerprint

fotemustine
Lymphangiogenesis
Angiogenesis Inducing Agents
Melanoma
Vascular Endothelial Growth Factor C
Serum
Therapeutics
Interleukin-23
Survival
Interleukins
Bevacizumab
Intravenous Administration
Interleukin-10
Vascular Endothelial Growth Factor A
Flow Cytometry
Cell Death
Research Design
Enzyme-Linked Immunosorbent Assay

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Bevacizumab plus fotemustine as first-line treatment in metastatic melanoma patients : Clinical activity and modulation of angiogenesis and lymphangiogenesis factors. / Del Vecchio, Michele; Mortarini, Roberta; Canova, Stefania; Di Guardo, Lorenza; Pimpinelli, Nicola; Sertoli, Mario R.; Bedognetti, Davide; Queirolo, Paola; Morosini, Paola; Perrone, Tania; Bajetta, Emilio; Anichini, Andrea.

In: Clinical Cancer Research, Vol. 16, No. 23, 01.12.2010, p. 5862-5872.

Research output: Contribution to journalArticle

Del Vecchio, M, Mortarini, R, Canova, S, Di Guardo, L, Pimpinelli, N, Sertoli, MR, Bedognetti, D, Queirolo, P, Morosini, P, Perrone, T, Bajetta, E & Anichini, A 2010, 'Bevacizumab plus fotemustine as first-line treatment in metastatic melanoma patients: Clinical activity and modulation of angiogenesis and lymphangiogenesis factors', Clinical Cancer Research, vol. 16, no. 23, pp. 5862-5872. https://doi.org/10.1158/1078-0432.CCR-10-2363
Del Vecchio, Michele ; Mortarini, Roberta ; Canova, Stefania ; Di Guardo, Lorenza ; Pimpinelli, Nicola ; Sertoli, Mario R. ; Bedognetti, Davide ; Queirolo, Paola ; Morosini, Paola ; Perrone, Tania ; Bajetta, Emilio ; Anichini, Andrea. / Bevacizumab plus fotemustine as first-line treatment in metastatic melanoma patients : Clinical activity and modulation of angiogenesis and lymphangiogenesis factors. In: Clinical Cancer Research. 2010 ; Vol. 16, No. 23. pp. 5862-5872.
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AU - Canova, Stefania

AU - Di Guardo, Lorenza

AU - Pimpinelli, Nicola

AU - Sertoli, Mario R.

AU - Bedognetti, Davide

AU - Queirolo, Paola

AU - Morosini, Paola

AU - Perrone, Tania

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AU - Anichini, Andrea

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