Abstract 5511: 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

Abstract 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. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5511. doi:10.1158/1538-7445.AM2011-5511