title: Gemcitabine, oxaliplatin, levofolinate, 5-fluorouracil, granulocyte-macrophage colony-stimulating factor, and interleukin-2 (GOLFIG) versus FOLFOX chemotherapy in metastatic colorectal cancer patients: the GOLFIG-2 multicentric open-label randomized phase III trial.
abstract: The GOLFIG-2 phase III trial was designed to compare the immunobiological activity and antitumor efficacy of GOLFIG chemoimmunotherapy regimen with standard FOLFOX-4 chemotherapy in frontline treatment of metastatic colorectal cancer (mCRC) patients. This trial was conceived on the basis of previous evidence of antitumor and immunomodulating activity of the GOLFIG regimen in mCRC. GOLFIG-2 is a multicentric open/label phase III trial (EUDRACT: 2005-003458-81). Chemo-naive mCRC patients were randomized in a 1:1 ratio to receive biweekly standard FOLFOX-4 or GOLFIG [gemcitabine (1000 mg/m(2), day 1); oxaliplatin (85 mg/m(2), day 2); levofolinate (100 mg/m(2), days 1-2), 5-fluorouracil (5-FU) (400 mg/m(2) in bolus followed by 24 h infusion at 800 mg/m(2),days 1-2), sc. GM-CSF (100 μg, days 3-7); sc. aldesleukin (0·5 MIU bi-daily, days 8-14 and 17-30)] treatments. The study underwent early termination because of poor recruitment in the control arm. After a median follow-up of 43.83 months, GOLFIG regimen showed superiority over FOLFOX in terms of progression-free survival [median 9·23 (95% confidence interval (CI), 6·9-11.5) vs. median 5.70 (95% CI, 3.38-8.02) months; hazard ratio (HR): 0.52 (95% CI, 0.35-0.77), P=0·002] and response rate [66.1% (95% CI, 0.41-0.73) vs. 37·0% (95% CI, 0.28-0.59), P=0.002], with a trend to longer survival [median 21.63 (95% CI, 18.09-25.18) vs. 14.57 mo (95% CI, 9.07-20.07); HR: 0·79 (95% CI, 0.52-1.21); P=0.28]. Patients in the experimental arm showed higher incidence of non-neutropenic fever (18.5%), autoimmunity signs (18.5%), an increase in the number of monocytes, eosinophils, CD4(+) T lymphocytes, natural killer cells, and a decrease in immunoregulatory (CD3(+)CD4(+)CD25(+)FoxP3(+)) T cells. Taken together, these findings provide proof-of-principle that GOLFIG chemoimmunotherapy may represent a novel reliable option for first-line treatment of mCRC.
authors: *Radiotherapy Unit §Medical Oncology Unit, Department of Oncology, Microbiology Section ∥Department of Biotechnology ¶Rheumatology Unit, Department of Medicine #Pharmacy Unit, Siena University Hospital "Santa Maria alle Scotte", Istituto Toscano Tumory, Siena †Medical Oncology Unit ‡Department of Legal, Historical, Economic and Social Sciences-DSGSES, Magna Graecia University of Catanzaro ††Translational Medical Oncology Unit, "Magna Graecia" University and "Tommaso Campanella" Cancer Center, Campus "Salvatore Venuta," Catanzaro **Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples ‡‡Chemotherapy Unit, Department of Oncology, Florence University School of Medicine, Florence §§Medical Oncology Unit, Department of Oncology, Cagliari University School of Medicine, Cagliari ∥∥Medical Oncology Unit, Centro Oncologico Romagnolo, Forlì, Italy.
authors: Pierpaolo
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authors: Correale
authors: Cirino
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authors: Botta
authors: Maria S
authors: MS
authors: Rotundo
authors: Annamaria
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authors: Guglielmo
authors: Raffaele
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authors: Conca
authors: Antonella
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authors: Licchetta
authors: Pierpaolo
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authors: Pastina
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authors: Bestoso
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authors: Ciliberto
authors: Maria G
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authors: Fioravanti
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authors: GM
authors: Guidelli
authors: Maria T
authors: MT
authors: Bianco
authors: Gabriella
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authors: Misso
authors: Elodia
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authors: Martino
authors: Michele
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authors: Caraglia
authors: Pierfrancesco
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authors: Tassone
authors: Enrico
authors: E
authors: Mini
authors: Giovanni
authors: G
authors: Mantovani
authors: Ruggero
authors: R
authors: Ridolfi
authors: Luigi
authors: L
authors: Pirtoli
authors: Pierosandro
authors: P
authors: Tagliaferri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage; D002955:Leucovorin / Q000008:administration & dosage / Q000627:therapeutic use; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D000077150:Oxaliplatin; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D007376:Interleukin-2; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002955:Leucovorin; D005472:Fluorouracil; D000093542:Gemcitabine