VACOP-B, high-dose cyclophosphamide and high-dose therapy with peripheral blood progenitor cell rescue for aggressive non-Hodgkin's lymphoma with bone marrow involvement: a study by the non-Hodgkin's Lymphoma Co-operative Study Group

Background and Objectives. Sequential treatment with the addition of high-dose therapy (HDT) and peripheral blood progenitor cell (PBPC) rescue has been reported to be active as front-line therapy in aggressive non-Hodgkin's lymphoma (NHL) with bone marrow (BM) involvement. We designed an intensive sequential therapy as front-line therapy in this subset of patients and conducted a phase II study. Design and Methods. Patients with aggressive non-Hodgkin's lymphoma and BM involvement at diagnosis received 8 weeks of VACOP-B chemotherapy as Induction therapy. The second phase included high-dose cyclophosphamide (HDCY) (7 g/m(2)) with granulocyte colony-stimulating factor (G-CSF) followed by leukaphereses. The third phase included HDT according to the BEAM protocol or melphalan (140 mg/m(2)) plus total body irradiation (8 Gy in a single dose). Results. Forty patients were Included in the study. According to the intention-to-treat, after VACOP-B, 11 (27.5%) and 22 (55%) patients achieved complete remission (CR) and partial remission (PR), respectively. Thirty-four received HDCY. After HDCY, 18 patients (45%) were in CR and 13 (32.5%) in PR. Twenty-nine underwent HDT plus peripheral blood cell rescue (PBPC) rescue. At the completion of treatment 29 patients (72.5%) were in CR, and 3 patients (7.5%) in PR. The actuarial 3-year overall survival, disease free survival and failure free sur vival are 48%, 55% and 40%, respectively. Overall severe toxicity was 7.5%. Interpretation and Conclusions. This phase tl study suggests that the intensified treatment described is feasible and active in aggressive NHL with BM involvement. A randomized trial is now underway to test this approach. (C)2000, Ferrata Storti Foundation.85216016

Thymic epithelial tumors express vascular endothelial growth factors and their receptors as potential targets of antiangiogenic therapy: A tissue micro array-based multicenter study

Objectives: Tumor angiogenesis is an essential and complex process necessary for the growth of all tumors which represents a potential therapeutic target. Angiogenesis inhibitors targeting vascular endothelial growth factor (VEGF) or their receptor tyrosine kinases have been approved by the FDA. In thymic epithelial tumors (TET), targeted therapies have been sporadically applied due to their rarity. To ascertain the presence of potential therapeutic targets, we analyzed by immunohistochemistry the expression of angiogenesis-related biomarkers in a large series of TET arranged in Tissue Micro Arrays (TMA). Materials and methods: We assessed by immunohistochemistry the expression of the possible molecular target of anti-angiogenic therapy, i.e. VEGFA, VEGFC, VEGFD, VEGFR1, VEGFR2, VEGFR3, and PDGFRβ, in a TMA series of 200 TET collected in the framework of a multi-institutional collaborative project for Rare Diseases. Results: When compared to the low-risk tumors, high-risk TET (B2, B3, carcinomas) contained higher proportion of cancer cells expressing VEGFA, VEGFC and VEGFD (P< 0.001, P< 0.001, and P< 0.001) growth factors, and their receptors VEGFR1 (P= 0.002), VEGFR2 (P= 0.013), and VEGFR3 (P= 0.041). No differences were observed in terms of PDGFRβ expression. Conclusions: According to our data, it is possible to hypothesize the existence of multiple paracrine and/or autocrine loops in TET, particularly in the high-risk ones, involved in TET growth and progression. Anti-angiogenic agents, directed to inhibit these loops, are therefore to be considered as potential tools in advanced TET therapy. © 2014 Elsevier Ireland Ltd.Abstract OBJECTIVES: Tumor angiogenesis is an essential and complex process necessary for the growth of all tumors which represents a potential therapeutic target. Angiogenesis inhibitors targeting vascular endothelial growth factor (VEGF) or their receptor tyrosine kinases have been approved by the FDA. In thymic epithelial tumors (TET), targeted therapies have been sporadically applied due to their rarity. To ascertain the presence of potential therapeutic targets, we analyzed by immunohistochemistry the expression of angiogenesis-related biomarkers in a large series of TET arranged in Tissue Micro Arrays (TMA). MATERIALS AND METHODS: We assessed by immunohistochemistry the expression of the possible molecular target of anti-angiogenic therapy, i.e. VEGFA, VEGFC, VEGFD, VEGFR1, VEGFR2, VEGFR3, and PDGFRβ, in a TMA series of 200 TET collected in the framework of a multi-institutional collaborative project for Rare Diseases. RESULTS: When compared to the low-risk tumors, high-risk