BACKGROUND: We designed a translational clinical trial to investigate whether a dose/dense chemotherapy regimen is able to enhance in patients with non-small-cell-lung-cancer (NSCLC) the anti-angiogenic effects of bevacizumab, a murine/human monoclonal antibody to the vasculo-endothelial-growth-factor (VEGF). We also evaluated the antitumor activity of this combination. RESULTS: The combined treatment induced a significant decline in the blood-perfusion of primary tumor (NMR-study); in serum levels of VEGF, angiopoietin-1, thrombospondin-1; and in the number of VEGF-transporting cells. In the group of 40 patients who received bevacizumab an objective response and a disease stabilization rate of 77.5% (95% CI, 75.63-93.17) and 15%, respectively, were recorded with a time to progression of 7.6 mo. Grade I-II hematological toxicity was the most common adverse event. Four early deaths within 3 mo, three cases of pneumonia, and six cases of mood depression at higher bevacizumab dosage were observed. The most active biological and maximum tolerated dose were 5 and 7.5 mg/kg, respectively. PATIENTS AND METHODS: Forty-eight patients (42 males and six females) with stage III B/IV NSCLC, a mean age of 68 y, and ECOG <or=2 were enrolled in the study. They received every 3 w fractioned cisplatinum (30 mg/sqm, days 1-3) and oral etoposide (50 mg, days 1-15) and were divided in five cohorts receiving different bevacizumab dosages (0; 2.5; 5; 7.5; and 10 mg/kg) on day 3. CONCLUSION: The combination of bevacizumab with a dose/dense chemotherapy regimen resulted moderately safe but showed significant anti-angiogenic and antitumor activity.
BACKGROUND: We designed a translational clinical trial to investigate whether a dose/dense chemotherapy regimen is able to enhance in patients with non-small-cell-lung-cancer (NSCLC) the anti-angiogenic effects of bevacizumab, a murine/human monoclonal antibody to the vasculo-endothelial-growth-factor (VEGF). We also evaluated the antitumor activity of this combination. RESULTS: The combined treatment induced a significant decline in the blood-perfusion of primary tumor (NMR-study); in serum levels of VEGF, angiopoietin-1, thrombospondin-1; and in the number of VEGF-transporting cells. In the group of 40 patients who received bevacizumab an objective response and a disease stabilization rate of 77.5% (95% CI, 75.63-93.17) and 15%, respectively, were recorded with a time to progression of 7.6 mo. Grade I-II hematological toxicity was the most common adverse event. Four early deaths within 3 mo, three cases of pneumonia, and six cases of mood depression at higher bevacizumab dosage were observed. The most active biological and maximum tolerated dose were 5 and 7.5 mg/kg, respectively. PATIENTS AND METHODS: Forty-eight patients (42 males and six females) with stage III B/IV NSCLC, a mean age of 68 y, and ECOG <or=2 were enrolled in the study. They received every 3 w fractioned cisplatinum (30 mg/sqm, days 1-3) and oral etoposide (50 mg, days 1-15) and were divided in five cohorts receiving different bevacizumab dosages (0; 2.5; 5; 7.5; and 10 mg/kg) on day 3. CONCLUSION: The combination of bevacizumab with a dose/dense chemotherapy regimen resulted moderately safe but showed significant anti-angiogenic and antitumor activity.
Authors: Osvaldo P Almeida; Andrew H Ford; Leon Flicker; Graeme J Hankey; Bu B Yeap; Paula Clancy; Jonathan Golledge Journal: J Psychiatry Neurosci Date: 2014-05 Impact factor: 6.186
Authors: M Huylebrouck; S Lv; J Duerinck; A Van Binst; I Salmon; J De Greve; O De Witte; S Luce; A Michotte; J D'Haens; B Neyns Journal: J Oncol Date: 2012-03-13 Impact factor: 4.375
Authors: C Botta; G Misso; E C Martino; L Pirtoli; M G Cusi; P Tassone; P Tagliaferri; M Caraglia; P Correale Journal: Cell Death Dis Date: 2016-07-21 Impact factor: 8.469
Authors: E C Martino; G Misso; P Pastina; S Costantini; F Vanni; C Gandolfo; C Botta; F Capone; A Lombardi; L Pirtoli; P Tassone; C Ulivieri; P Tagliaferri; M G Cusi; M Caraglia; P Correale Journal: Cell Death Discov Date: 2016-10-03