Immunological and anti-tumor activity of a novel a chemo-immunotherapy regimen with gemcitabine, oxaliplatin, levo-folinic acid, and 5-fluorouracil followed by GM-CSF and Interleukin-2 in patients with metastatic colorectal cancer

Abstract

2538 Background: Gemcitabine + FOLFOX-4 (GOLF) regimen is a powerful multi-drug regimen which is able to determine molecular changes in colon cancer cells that make them a powerful means to induce an antigen specific CTL response in human PBMCs in vitroif taken up and processed by dendritic cells (DCs). We also showed that cancer patients’ activated DCs and CTL response may be induced with the subcutaneous (sc.) administration of GM-CSF and low dose IL-2 (IG-1 regimen). All together these results offered the rationale to design an original chemo immunotherapy protocol in colon cancer patients. Methods: We designed a phase II trial aimed to evaluate in metastatic colorectal carcinoma patients, the toxicity, the anti-tumor and the immunological activity of GOLF regimen [intravenous (iv.) GEM (1g/m2) - day 1 and 15; iv. levo-folinic acid (LF, 100 mg/m2) + iv. bolus (400 mg/m2) and 24 hour-infusional (800 mg/m2) 5-FU - day 1,2, 15,16-; and iv. 6–8 hour infusional oxaliplatin (85 mg/m2) - day 2 and 16, before LF/5-FU administration] combined with IG-1 immunotherapy [sc.GM-CSF (100 μg/day -days 3→7) and sc.IL-2 (0.5 MIU twice a day, days 8→14 and 17→30]. Twenty nine patients, 16 males and 13 females, with an average age of 69 years and an ECOG ≤ 2 were enrolled; among these, 21 had received a previous line of treatment, and 19 had liver involvement. Results: The treatment was well tolerated and induced a very high rate of objective responses (68.9%%) and disease control (96.5%), with a median time to progression of 12.5 months. An immunological study demonstrated the treatment ability to enhance a cell mediated immune response to colon carcinoma antigens and reduce the expression of regulatory T lymphocytes Conclusions: These results show that the GOLFIG regimen determines a strong immunological and anti-tumor activity in colorectal cancer patients and deserves to be investigated in future comparative phase III trials. No significant financial relationships to disclose.