Dose/dense metronomic chemotherapy with fractioned cisplatin and oral daily etoposide enhances the anti-angiogenic effects of bevacizumab and has strong antitumor activity in advanced non-small-cell-lung cancer patients
| Autor: | Pierpaolo, Correale, Cinzia, Remondo, Salvatore Francesco, Carbone, Veronica, Ricci, Cristina, Migali, Ignazio, Martellucci, Antonella, Licchetta, Raffaele, Addeo, Luca, Volterrani, Giuseppe, Gotti, Maria Saveria, Rotundo, Pierfrancesco, Tassone, Pasquale, Sperlongano, Alberto, Abbruzzese, Michele, Caraglia, Pierosandro, Tagliaferri, Guido, Francini |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Vascular Endothelial Growth Factor A Lung Neoplasms Maximum Tolerated Dose Administration Oral Enzyme-Linked Immunosorbent Assay Adenocarcinoma Antibodies Monoclonal Humanized Carcinoma Non-Small-Cell Lung Antineoplastic Combined Chemotherapy Protocols Angiopoietin-1 Humans Prospective Studies Aged Etoposide Aged 80 and over Antibodies Monoclonal Drug Synergism Middle Aged Bevacizumab Survival Rate Treatment Outcome Carcinoma Squamous Cell Female Cisplatin Thrombospondins |
| Zdroj: | Cancer biologytherapy. 9(9) |
| ISSN: | 1555-8576 |
| Popis: | 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.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.Forty-eight patients (42 males and six females) with stage III B/IV NSCLC, a mean age of 68 y, and ECOGor=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.The combination of bevacizumab with a dose/dense chemotherapy regimen resulted moderately safe but showed significant anti-angiogenic and antitumor activity. |
| Databáze: | OpenAIRE |
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