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Gentile M.,Unita Operativa Complessa di Ematologia | Recchia A.G.,Unita Operativa Complessa di Ematologia | Mazzone C.,Unita Operativa Complessa di Ematologia | Vigna E.,Unita Operativa Complessa di Ematologia | And 8 more authors.
Expert Opinion on Pharmacotherapy | Year: 2013

Introduction: Bendamustine is a unique bifunctional alkylating agent with promising activity in multiple myeloma (MM). It is currently licensed in Europe for use as frontline treatment with prednisolone for patients with MM who are unsuitable for transplantation and who are contraindicated for thalidomide and bortezomib therapy. Areas covered: Studies evaluating the safety and efficacy of bendamustine administered alone or in combination in both the upfront and relapse settings of MM patients, including those with renal insufficiency, were reviewed. The use of bendamustine as conditioning for autologous stem-cell transplantation and the possibility of stem-cell mobilization after bendamustine therapy are discussed. Expert opinion: Bendamustine seems to be efficacious either in monotherapy or in combination with other drugs in previously treated or untreated patients. This is due to its unique mechanism of action including its ability to activate apoptosis and inhibit mitotic checkpoints, making it potentially more effective than other alkylating agents. Moreover, it has an acceptable toxicity profile and is suitable for patients with renal impairment. Finally, this drug does not seem to compromise the possibility of achieving a stem-cell mobilization. Nonetheless, data from Phase III studies demonstrating its effectiveness in terms of overall survival are not yet available. © Informa UK, Ltd.

Gentile M.,Hematology Unit | Martino M.,Hematology and Stem Cell Transplant Unit | Recchia A.G.,U.S. Department of Agriculture | Vigna E.,U.S. Department of Agriculture | And 3 more authors.
Expert Opinion on Investigational Drugs | Year: 2016

Introduction: Sorafenib is an orally available compound that acts predominantly by targeting the Ras/Raf/MEK/ERK pathway and by inhibiting the vascular endothelial growth factor (VEGF). Since the Ras/Raf/MEK/ERK pathway is implicated in the proliferation of multiple myeloma (MM) cells and VEGF in bone marrow neovascularization, sorafenib is a drug offering the potential for targeting two important pathogenetic mechanisms involved in MM. Thus, sorafenib is being proposed for use in MM. Areas covered: In this review, the authors discuss the rationale for the use of sorafenib in MM. They then summarize the clinical development of sorafenib in MM, from initial Phase I to Phase II studies. A systematic literature review of the trials was performed using PubMed. Expert opinion: Preliminary data from phase I/II trials showed that sorafenib had a good safety profile but minimal anti-myeloma activity as a single agent in relapsed/refractory patients. Results of phase II trials, evaluating sorafenib combined with new drugs, such as bortezomib and lenalidomide are eagerly awaited. © 2016 Informa UK Limited, trading as Taylor & Francis Group.

Gentile M.,Haematology Unit | Vigna E.,Haematology Unit | Recchia A.G.,Haematology Unit | Morabito L.,Medical oncology and hematology unit | And 3 more authors.
European Journal of Haematology | Year: 2015

The advent of high-dose melphalan with autologous stem-cell transplantation (ASCT), the availability of novel agents such as thalidomide, lenalidomide (immunomodulatory drugs or IMiDs) and bortezomib (proteasome inhibitor) and improvements in supportive care have allowed to increase overall survival in multiple myeloma (MM) patients; nevertheless, MM remains an incurable pathology. For this reason, newer agents are required for continued disease control. Bendamustine is an old drug rediscovered in the last decade. In fact, its unique mechanism of action with structural similarities to both alkylating agents and antimetabolities, but which is not cross-resistant to alkylating agents, has reawakened interest in the use of this drug in the treatment of MM. Studies have proven the safety and efficacy of bendamustine administered alone or in combination with new drugs in both upfront and relapse/refractory settings of MM patients, including those with renal impairment. Moreover, bendamustine has been successfully used as conditioning for autologous stem-cell transplantation. Finally, the use of bendamustine does not compromise peripheral blood stem-cell collection. This drug is generally well tolerated, with the majority of adverse events being due to myelosuppression. Non-haematological adverse events are infrequent and usually mild. © 2015 John Wiley & Sons A/S.

Ibatici A.,Medical oncology and hematology unit | Caviggioli F.,University of Milan | Valeriano V.,University of Milan | Quirici N.,University of Milan | And 6 more authors.
Aesthetic Plastic Surgery | Year: 2014

Background: Autologous fat grafting is a widely adopted surgical technique in both the reconstructive and aesthetic fields. This study aimed to compare centrifuged lipoaspirates harvested and refined by the Coleman technique with noncentrifuged lipoaspirates in terms of cell number and viability, phenotypic profile, and clonogenic and proliferative potential of adipose-derived stem cell (ADSC) populations.Methods: For each patient, both a centrifuged sample using the Coleman’s technique and a noncentrifuged sample of adipose tissue were collected. Adipose-derived stem cells from both the centrifuged fraction (CF) and the noncentrifuged fraction (NCF) were isolated. The recovered ADSCs were used to set up flow cytometry analysis, colony-forming units–fibroblast (CFU-F) assays, and ADSC cultures.Results: The number of recovered cells was variable among the different donors but significantly higher in the CF donors. Cell viability, determined by the Trypan Blue dye assay, always exceeded 95 %, in both the CF and NCF fractions. Analysis of the putative ADSC subpopulations showed a significant enrichment of the mesenchymal and endothelial progenitors in CF compared with NCF. No differences in the clonogenic efficiency of the ADSC samples were observed when the same number of cells were plated from each fraction. On the contrary, when equal fat volumes were compared, the colony-forming ability of CF was always significantly higher than that of its NCF counterparts.Conclusions: This is the first study to comprehensively characterize the impact of Coleman’s technique on the quality of lipoaspirates, showing that centrifugation is safe and feasible and does not impair cell viability, can augment the content in ADSC and the frequency of CFU-F, and reduces the number of proinflammatory blood cells.No Level Assigned: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266. © 2014, Springer Science+Business Media New York and International Society of Aesthetic Plastic Surgery.

Rimassa L.,Medical oncology and hematology unit | Pressiani T.,Medical oncology and hematology unit | Boni C.,Medical Oncology | Carnaghi C.,Medical oncology and hematology unit | And 13 more authors.
Oncologist | Year: 2013

Background. Sorafenib has proven survival benefits in patients with advanced hepatocellular carcinoma (HCC). The viability of continuing sorafenib at a higher dosage in patients who experienced radiologic disease progression was investigated. Methods. Patients who experienced disease progression while on sorafenib 400 mg twice daily were randomized to sorafenib 600mgtwice daily (n49) or best supportive care (n52). The primary end point was progression-free survival (PFS). Time to progression, overall survival,andsafetywerealso evaluated. Results. The study did not meet its primary end point. The difference in PFS between the sorafenib arm (3.91 months) and the best supportive care arm (2.69 months) did not reach statistical significance (p = 0.086). Adverse events were mainly grade 1-2 and similar across both groups. In the sorafenib arm, the most frequent events were diarrhea (80%), weight loss (75%), fatigue (67%), hand-foot-skin reaction (49%), abdominal pain (37%), and stomatitis (26%). Conclusions. Escalated-dose sorafenib in patients with advanced HCC who progressed while on sorafenib, failed to provide any clinical benefit. Second-line treatment still remains an open issue to be explored in appropriate clinical trials © AlphaMed Press 2013.

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