6533b7d4fe1ef96bd1261e2f

RESEARCH PRODUCT

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.

Giacomo Maria GuidelliMaria Saveria RotundoEnrico MiniDomenico CilibertoMaria T. BiancoAntonella LicchettaElena BestosoCirino BottaGabriella MissoRuggero RidolfiPierpaolo PastinaMichele CaragliaAntonella FioravantiAnnamaria GuglielmoLuigi PirtoliGiovanni MantovaniPierfrancesco TassonePierosandro TagliaferriElodia Claudia MartinoPierpaolo CorrealeMaria Grazia CusiRaffaele Conca

subject

OncologyMaleCancer ResearchGranulocyte-macrophage-colonystimulating- factorOrganoplatinum Compoundsmedicine.medical_treatmentLeucovorinColorectal NeoplasmGastroenterologyDeoxycytidineFOLFOXAldesleukinPhase iii trialAntineoplastic Combined Chemotherapy ProtocolsImmunology and AllergyMedicineChemoimmunotherapyNeoplasm MetastasisAged 80 and overAldesleukinMiddle AgedNeoplasm MetastasiOxaliplatinColorectal carcinomaTreatment OutcomeFluorouracilFemaleFluorouracilColorectal NeoplasmsHumanmedicine.drugAdultmedicine.medical_specialtyImmunologyLymphocytes Tumor-InfiltratingChemoimmunotherapyInternal medicineHumansAgedPharmacologyChemotherapyAntineoplastic Combined Chemotherapy Protocolbusiness.industryOrganoplatinum CompoundGranulocyte-Macrophage Colony-Stimulating FactorGemcitabineGemcitabineOxaliplatinRegimenInterleukin-2Neoplasm Gradingbusiness

description

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/m2, day 2); levofolinate (100 mg/m2, days 1-2), 5-fluorouracil (5-FU) (400 mg/m2 in bolus followed by 24 h infusion at 800 mg/m2,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. 14.57mo (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 proofof- principle that GOLFIG chemoimmunotherapy may represent a novel reliable option for first-line treatment of mCRC. Copyright © 2014 by Lippincott Williams & Wilkins.

yearjournalcountryeditionlanguage
2013-12-10Journal of immunotherapy (Hagerstown, Md. : 1997)
10.1097/cji.0000000000000004https://pubmed.ncbi.nlm.nih.gov/24316553