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Immunity Feedback and Clinical Outcome in Colon Cancer Patients Undergoing Chemoimmunotherapy with Gemcitabine + FOLFOX followed by Subcutaneous Granulocyte Macrophage Colony-Stimulating Factor and Aldesleukin (GOLFIG-1 Trial)

Authors' Affiliations: ¹ Section of Medical Oncology, Department "Giorgio Segre" of Pharmacology, ² Rheumatology Unit, Department of Clinical Medicine and Immunological Sciences, ³ Pathology Section, Department of Human Pathology and Oncology, and ⁴ Section of Microbiology, Department of Molecular Biology, Siena University School of Medicine, Siena, Italy; and ⁵ Medical Oncology Unit, "Campus Salvatore Venuta," "Magna Graecia University, School of Medicine," Catanzaro, Italy

Requests for reprints: Guido Francini, Section of Medical Oncology, Division of Medical Oncology, Siena University School of Medicine, Viale Bracci 11, 53100 Siena, Italy. Phone: 39-0577-586369; Fax: 39-0577-586133; E-mail: correale{at}unisi.it.

Purpose: GOLFIG chemoimmunotherapy regimen proved to be a safe and very active chemoimmunotherapy regimen in advanced colon cancer patients. We have thus investigated the immunobiological feedback to the treatment and its possible correlation with the clinical outcome of these patients.

Experimental Design: This clinical and immunologic study involved 46 patients, 27 males and 19 females, enrolled in the GOLFIG-1 phase II trial who received gemcitabine (1,000 mg/m² on days 1 and 15), oxaliplatin (85 mg/m² on days 2 and 16), levofolinic acid (100 mg/m² on days 1, 2, 15, and 16), and 5-fluorouracil (400 mg/m² as a bolus, and 800 mg/m² as a 24-hour infusion on days 1, 2, 15, and 16) followed by s.c. granulocyte macrophage colony-stimulating factor (100 µg, on days 3-7) and interleukin 2 (0.5 x 10⁶ IU twice a day on days 8-14 and 17-29).

Results: The regimen was confirmed to be safe and very active in pretreated patients with metastatic colorectal cancer. A subgroup analysis of these patients revealed a prolonged time to progression and survival in six patients who developed late signs of autoimmunity. A multivariate analysis validated the occurrence of autoimmunity signs as an independent predictor of favorable outcome. A parallel immunologic study detected in the peripheral blood mononuclear cells of these patients a progressive increase in lymphocyte and eosinophil counts, amplification in central memory, a marked depletion of immunosuppressive regulatory T cells, and activation of colon cancer–specific cytotoxic T cells.

Conclusions: Our results suggest that immunity feedback to GOLFIG regimen and its antitumor activity are tightly correlated.