Bevacizumab plus Fotemustine as First-line Treatment in Metastatic Melanoma Patients: Clinical Activity and Modulation of Angiogenesis and Lymphangiogenesis Factors

Vecchio, Michele Del; Mortarini, Roberta; Canova, Stefania; Guardo, Lorenza Di; Pimpinelli, Nicola; Sertoli, M. R.; Bedognetti, Davide; Queirolo, Paola; Morosini, Paola; Perrone, Tania; Bajetta, Emilio; Anichini, Andrea

doi:10.1158/1078-0432.ccr-10-2363

Cited by 56 publications

(32 citation statements)

References 36 publications

(1 reference statement)

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“…Recently Del Vecchio [133] investigated the modulation of bevacizumab administration in metastatic melanoma patients and evaluated the angiogenesis modulation. This study showed that serum VEGF-A and overall proangiogenic activity were significantly inhibited.…”

Section: Predictive Markers and New Drugsmentioning

confidence: 99%

Role of Angiogenesis Inhibitors in Colorectal Cancer: Sensitive and Insensitive Tumors

Bagnasco

Piras²,

Parodi

et al. 2012

CCDT

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Angiogenesis is a key factor in the carcinogenesis process. In oncological practice, angiogenesis inhibition, mainly through the blockade of the VEGF family and its receptors, has been robustly demonstrated to produce clinical benefits and, in specific disease subsets such as colorectal cancer, to extend the overall survival of treated patients. VEGF is a multifunctional growth factor that mediates its functions through cognate receptors on endothelial cells and it has been discovered for its capability to induce macromolecule hyperpermeability in veins and venules. Several approaches have been taken to target angiogenesis in cancer: drugs that target one or more soluble ligands of the VEGF family, drugs that selectively inhibit one or more receptors of the VEGF receptor family, and drugs that inhibit VEGF receptor(s) among other, non VEGF-related targets. At present, two compounds have shown significant clinical activity, bevacizumab, Avastin® and aflibercept, Zaltrap®, and only one of these (bevacizumab) has so far been registered for use in clinical practice. In the present review, we explore and summarize the main features of the angiogenetic process, concerning in particular a common and potentially lethal disease as colorectal cancer. We overview the molecular pathways that characterize angiogenesis, focusing on VEGF family, the current applications and limitations of its blockade in oncology, and the hypothetical future perspectives of anti-angiogenic therapy.

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Section: Predictive Markers and New Drugsmentioning

confidence: 99%

Role of Angiogenesis Inhibitors in Colorectal Cancer: Sensitive and Insensitive Tumors

Bagnasco

Piras²,

Parodi

et al. 2012

CCDT

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“…All serum samples were evaluated in duplicate. Briefly, sera from the patients and controls were incubated with biotinylated antibodies as described previously (36). Next, streptavidin-horseradish peroxidase (SA-HRP) was added.…”

Section: Serum Biomarker Analysismentioning

confidence: 99%

“…In addition, this study also investigated a variety of predictive biomarkers, including (i) ERK and AKT phosphorylation in peripheral blood lymphocytes (PBL; refs. [33][34][35] and (ii) serum levels of cytokines involved in angiogenesis and lymphangiogenesis (36).…”

Section: Introductionmentioning

confidence: 99%

Phase II Study of Perifosine and Sorafenib Dual-Targeted Therapy in Patients with Relapsed or Refractory Lymphoproliferative Diseases

Guidetti

Carlo‐Stella

Locatelli

et al. 2014

Clinical Cancer Research

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Purpose: To evaluate safety and activity of perifosine and sorafenib combination therapy in patients with lymphoproliferative diseases.Experimental Design: Patients with relapsed and refractory lymphoproliferative diseases received perifosine (50 mg twice daily) for 1 month. Patients achieving less than partial response (PR) after perifosine alone were administered the combination therapy [perifosine plus sorafenib (400 mg twice daily)] until progressive disease (PD) or unacceptable toxicity occurred. The pERK and pAKT in peripheral blood lymphocytes as well as serum cytokine levels were investigated as predictive biomarkers of response.Results: Forty patients enrolled in this study. After 1 month of perifosine alone, 36 who achieved less than PR went on to combination therapy, whereas four patients with chronic lymphocytic leukemia (CLL) who achieved PR continued with perifosine alone for a median of 10 months (range, 4-21). The most common drug-related toxicities were grade 1-2 anemia (17%), thrombocytopenia (9%), diarrhea (25%), joint pain (22%), and hand-foot skin reaction (25%). Three patients experienced grade 3 pneumonitis. Eight patients (22%) achieved PR, 15 (42%) achieved stable disease, and 13 (36%) experienced PD. A 28% PR rate was recorded for 25 patients with Hodgkin lymphoma. Among all patients, median overall survival and progression-free survival were 16 and 5 months, respectively. Early reductions in pERK and pAKT significantly correlated with the probability of clinical response.Conclusions: Perifosine and sorafenib combination therapy is feasible with manageable toxicity and demonstrates promising activity in patients with Hodgkin lymphoma. The predictive value of pERK and pAKT should be confirmed in a larger patient cohort.

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“…Phase II studies have shown some activity against melanoma in combination with IFN and fotmustine. 13 A large Phase III study is ongoing to assess efficacy of response to therapy with bevacizumab in the adjuvant setting for surgically resected advanced disease (AVAST-M study).…”

Section: Antibodies Targeting Vascular Endothelial Growth Factormentioning

confidence: 99%

Advances in the treatment of melanoma

2012

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Bevacizumab plus Fotemustine as First-line Treatment in Metastatic Melanoma Patients: Clinical Activity and Modulation of Angiogenesis and Lymphangiogenesis Factors

Cited by 56 publications

References 36 publications

Role of Angiogenesis Inhibitors in Colorectal Cancer: Sensitive and Insensitive Tumors

Role of Angiogenesis Inhibitors in Colorectal Cancer: Sensitive and Insensitive Tumors

Phase II Study of Perifosine and Sorafenib Dual-Targeted Therapy in Patients with Relapsed or Refractory Lymphoproliferative Diseases

Advances in the treatment of melanoma

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