Bruera et al. BMC Cancer 2010, 10:567 http://www.biomedcentral.com/1471-2407/10/567 R E S E A R C H A R T I C L E Open Access “Poker” association of weekly alternating 5-fluorouracil, irinotecan, bevacizumab and oxaliplatin (FIr-B/FOx) in first line treatment of metastatic colorectal cancer: a phase II study Gemma Bruera1†, Alessandra Santomaggio1†, Katia Cannita1, Paola Lanfiuti Baldi1, Marianna Tudini1, Federica De Galitiis2, Maria Mancini1, Paolo Marchetti3, Adelmo Antonucci4, Corrado Ficorella1, Enrico Ricevuto1* Abstract Background: This phase II study investigated efficacy and safety of weekly alternating Bevacizumab (BEV)/ Irinotecan (CPT-11) or Oxaliplatin (OHP) associated to weekly 5-Fluorouracil (5-FU) in first line treatment of metastatic colorectal carcinoma (MCRC). Methods: Simon two-step design: delta 20% (p0 50%, p1 70%), power 80%, a 5%, b 20%. Projected objective responses (ORR): I step, 8/15 patients (pts); II step 26/43 pts. Schedule: weekly 12 h-timed-flat-infusion/5-FU 900 mg/m2, days 1-2, 8-9, 15-16, 22-23; CPT-11 160 mg/m2 plus BEV 5 mg/kg, days 1,15; OHP at three dose-levels, 60-70-80 mg/m2, days 8, 22; every 4 weeks. Results: Fifty consecutive, unselected pts < 75 years were enrolled: median age 63; young-elderly (yE) 24 (48%); liver metastases (LM) 33 pts, 66% Achieved OHP recommended dose, 80 mg/m2. ORR 82% intent-to-treat and 84% as-treated analysis. Median progression-free survival 12 months. Equivalent efficacy was obtained in yE pts. Liver metastasectomies were performed in 26% of all pts and in 39% of pts with LM. After a median follow-up of 21 months, median overall survival was 28 months. Cumulative G3-4 toxicities per patient: diarrhea 28%, mucositis 6%, neutropenia 10%, hypertension 2%. They were equivalent in yE pts. Limiting toxicity syndromes (LTS), consisting of the dose-limiting toxicity, associated or not to G2 or limiting toxicities: 44% overall, 46% in yE. Multiple versus single site LTS, respectively: overall, 24% versus 20%; yE pts, 37.5% versus 8%. Conclusion: Poker combination shows high activity and efficacy in first line treatment of MCRC. It increases liver metastasectomies rate and can be safely administered. Trial registration: Osservatorio Nazionale sulla Sperimentazione Clinica dei Medicinali (OsSC) Agenzia Italiana del Farmaco (AIFA) Numero EudraCT 2007-004946-34 Background Over the last 15 years, multiple active drugs were used in doublet or triplet combinations of chemotherapy and/ or anti-targets, as first or subsequent lines of treatment [1-12] and increased overall survival of MCRC pts. Doublet combinations of 5-FU or Capecitabine asso- ciated to CPT-11 or OHP or BEV achieve ORR 40%, * Correspondence: enrico.ricevuto@univaq.it † Contributed equally 1Medical Oncology, S. Salvatore Hospital, University of L’Aquila, L’Aquila, Italy Full list of author information is available at the end of the article progression free survival (PFS) 6-9 months and overall survival (OS) 15-22 months [1-11]. The addition of BEV to 5-FU or CPT-11/5-FU/Leucovorin (IFL) significantly increased, respectively: ORR up to 34.1% and 44.8%; PFS up to 8.8 and 10.6 months; median OS up to 17.9 and 20.3 months [8-11]. Advantages were also demonstrated with the addition of BEV to OHP-containing regimens; 5-FU (bolus plus infusion) or Capecitabine and OHP plus BEV showed PFS 10 months and OS 26 months [13-16]. Triplet association of chemotherapy, FOLFOXIRI, also demon- strated, in a phase III study, a statistically significant © 2010 Bruera et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.