title: Phase II trial of bevacizumab and dose/dense chemotherapy with cisplatin and metronomic daily oral etoposide in advanced non-small-cell-lung cancer patients.
abstract: Bevacizumab, is a humanized monoclonal antibody to vasculo-endothelial-growth-factor, with anticancer activity in non-small-cell-lung cancer (NSCLC) patients. Our previous results from a dose/finding phase I trial in NSCLC patients, demonstrated the anti-angiogenic effects and toxicity of a newest bevacizumab-based combination with fractioned cisplatin and daily oral etoposide. We designed a phase II trial to evaluate in advanced NSCLC patients the antitumor activity and the safety of this novel regimen. In particular, 45 patients (36 males and 9 females), with a mean age of 54 years, an ECOG ≤ 2, stage IIIB/IV and NSCLC (28 adenocarcinomas, 11 squamous-cell carcinomas, 2 large-cell carcinomas, 4 undifferentiated carcinomas), were enrolled. They received cisplatin (30 mg/sqm, days 1-3), oral etoposide (50 mg, days 1-15) and bevacizumab (5 mg/kg, day 3) every three weeks (mPEBev regimen). Patients who achieved an objective response or stable disease received maintenance treatment with bevacizumab in combination with erlotinib until progression. Grade I-II hematological, mucosal toxicity and alopecia were the most common adverse events. The occurrence of infections (17%), thromboembolic events (4.4%) and severe mood depression (6.7%) was also recorded. A partial response was achieved in 31 (68.8%) patients, disease remained stable in 8 (17.8%), and disease progressed in 6 (13.3%) with a progression-free-survival of 9.53 months (95%CI, 7.7-11.46). Our bio-chemotherapy regimen resulted very active in advanced NSCLC, however, the toxicity associated with the treatment requires strict selection of the patients to enroll in future studies.
authors.affiliation: Medical Oncology Unit, Siena University Hospital Santa Maria alle Scotte, Istituto Toscano Tumori, Italy.
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Correale
authors.forename: Cirino
authors.initials: C
authors.lastname: Botta
authors.forename: Assunta
authors.initials: A
authors.lastname: Basile
authors.forename: Marco
authors.initials: M
authors.lastname: Pagliuchi
authors.forename: Antonella
authors.initials: A
authors.lastname: Licchetta
authors.forename: Ignazio
authors.initials: I
authors.lastname: Martellucci
authors.forename: Elena
authors.initials: E
authors.lastname: Bestoso
authors.forename: Serena
authors.initials: S
authors.lastname: Apollinari
authors.forename: Raffaele
authors.initials: R
authors.lastname: Addeo
authors.forename: Gabriella
authors.initials: G
authors.lastname: Misso
authors.forename: Ornella
authors.initials: O
authors.lastname: Romano
authors.forename: Alberto
authors.initials: A
authors.lastname: Abbruzzese
authors.forename: Monica
authors.initials: M
authors.lastname: Lamberti
authors.forename: Luca
authors.initials: L
authors.lastname: Luzzi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gotti
authors.forename: Maria Saveria
authors.initials: MS
authors.lastname: Rotundo
authors.forename: Michele
authors.initials: M
authors.lastname: Caraglia
authors.forename: Pierosandro
authors.initials: P
authors.lastname: Tagliaferri
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D000068258:Bevacizumab; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D005047:Etoposide; D002945:Cisplatin