Presentation Abstract

Abstract Number: 5511
Presentation Title: Chemo-immunotherapy with gemcitabine + FOLFOX followed by granulocyte-macrophage colony stimulating factor and low dose aldesleukine (GOLFIG regimen) is a highly active frontline treatment for advanced colorectal carcinoma: Results from the GOLFIG/2 phase III trial
Presentation Time: Wednesday, Apr 06, 2011, 8:00 AM -12:00 PM
Location: Exhibit Hall A4-C, Poster Section 32
Poster Section: 32
Poster Board Number: 6
Author Block: Pierpaolo Correale1, Maria Teresa Rotundo2, Cirino Botta1, Serena Apollinari1, Cinzia Remondo1, Kwong Yok Tsang3, Domenico Ciliberto4, Pierfrancesco Tassone4, Ruggero Ridolfi5, Pierosandro Tagliaferri4. 1Laboratory of Translational Immune Oncology, Section of Medical Oncology, Siena, Italy; 2Medical Oncology Unit, Campus Salvatore Venuta, Catanzaro, Italy; 3Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, MD; 4Medical Oncology Unit, Campus, Catanzaro, Italy; 5IRST, Forlì, Italy
Abstract Body: Background: previous clinical studies demonstrated the safety, the immunological and anti-tumor activity of a newest chemo-immunotherapy regimen with gemcitabine + FOLFOX followed by sc. granulocyte-macrophage Colony stimulating Factor and low dose sc aldesleukine (GOLFIG regimen) in pretreated advanced colorectal carcinoma patients. This regimen was designed on translational bases to mimic in cancer patients, a successful protocol for the in vitro generation of tumor specific T cell lines. We therefore, designed a phase-III trial in advanced colon carcinoma patients to compare the anti-tumor efficacy of GOLFIG regimen with standard FOLFOX-4 chemotherapy. Patients and Methods: GOLFIG/2 is a multicenter open label randomized phase-III trial. The study was designed on the hypothesis of a two months advantage of GOLFIG over FOLFOX-4 regimen in term of progression free survival (PFS). It was allowed an alpha and beta error of 0.05 (5%) and 0, 2 (80%), respectively. Patients were randomized in a 1:1 ratio in the two arms. Patients enrolled in the control arm received standard FOLFOX-4 poly-chemotherapy, while those enrolled in the experimental arm, received gemcitabine (1000 mg/m2, day 1, 15); oxaliplatin (85 mg/m2, day 2, 16); levo-folinate (100 mg/m2, days 1-2, 15-16), 5-FU (400 mg/m2 in bolus followed by 24 h infusion at 800 mg/m2, days 1-2, 15-16), sc. GM-CSF (100 µg, days 3-7); sc. aldesleukine (0.5 MIU bi-daily, days 8-14 and 17-30) day 1-15. One hundred thirty patients were enrolled between September 2005 and January 2010. The study was prematurely terminated because GOLFIG arm demonstrated a significantly longer PFS at the first preplanned interim analysis. Both FOLFOX-4 and GOLFIG regimens resulted safe, showing a similar range of adverse events mainly represented by grade I-II hematological toxicity, mucositis, and neurotoxicity. In the experimental arm, it was recorded a high frequency of aldesleukine-related fever, and self-limiting signs of autoimmunity in 16% of the patients. The GOLFIG regimen showed significant superiority over FOLFOX chemotherapy in term of response rate [59.3 (95%CI; 0.41-0.73) vs 34.4%, (95%CI; 0.28-0.59), P = 0.0001] and PFS [12.4 (95%CI- 9.3-15.6) vs 7.9 (95% CI 6.1-9.6) months; HR=0.64; P= 0.0105]. COX analysis indicated that performance status, autoimmunity, tumor infiltration by regulatory T cells (CD4+FoxP3+) and central memory T cells (CD8+CD45Ro-CCR7+) were independent predictive markers of favorable outcome. There was no correlation with either tumor site, histotype, grading, k-ras-mutational status or specific metastatic sites.Conclusion: the GOLFIG regimen is the first chemo-immunotherapy regimen which demonstrated efficacy in the frontline treatment of colorectal carcinoma.