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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.01102

GOLFIG chemo-immunotherapy in metastatic colorectal cancer (mCRC) patients. A critical review on a long lasting follow up.

 Michele Caraglia1*,  Pierpaolo Correale2*, Rocco Giannicola2, Nicoletta Staropoli3*,  Cirino Botta3, Pierpaolo Pastina4, Antonello Nesci5, Nadia Caporlingua5, Edoardo Francini6, Laura Ridolfi7, Enrico Mini8,  Giandomenico Roviello8, Domenico Ciliberto3, Rita M. Agostino2, Alessandra Strangio2, Domenico Azzarello2,  VALERIO NARDONE4, Antonia C. Falzea2, Salvatore Cappabianca1, 9,  Marco Bocchetti1, 9, Graziella D’Arrigo10, Giovanni Tripepi10,  Pierfrancesco Tassone3, Raffaele Addeo11, Antonio Giordano12, Luigi Pirtoli12, Guido Francini6 and  Pierosandro Tagliaferri3
  • 1University of Campania Luigi Vanvitelli, Italy
  • 2Department on Oncology, Hematology and Radiotherapy, Bianchi-Melacrino-Morelli Hospital of Reggio Calabria, Italy
  • 3Department of Clinical and Experimental Medicina, University of Magna Græcia di Catanzaro studios, Italy
  • 4Radiotherapy Unit, Department of Oncology, University Hospital of Siena, Italy
  • 5Bianchi Melacrino Morelli Grand Metropolitan Hospital, Italy
  • 6Siena University Hospital, Italy
  • 7Romagnolo Scientific Institute for the Study and Treatment of Tumors (IRCCS), Italy
  • 8Division of Clinical Pharmacology and Oncology, Department of Health Sciences, School of Psychology, University of Florence, Italy
  • 9University of Campania Luigi Vanvitelli, Italy
  • 10Institute of Clinical Physiology, Italian National Research Council, Italy
  • 11ASL Napoli 2 Nord, Italy
  • 12Department of Biology, College of Science and Technology, Temple University, United States

Background: GOLFIG is a chemo-immunotherapy regimen established in preclinical models which combines gemcitabine + FOLFOX poly-chemotherapy with low dose s.c. recombinant interleukin-2 (rIL-2) and granulocyte-macrophage Colony Stimulating Factor (GM-CSF). Promising antitumor effects in mCRC patients were obtained in previous Phase II and III trials. Here we report the results of fifteen years of follow up.
Methods: This is a multi-institutional retrospective analysis including 179 mCRC patients receiving GOLFIG regimen between June 2002 and June 2018. Sixty-two of them received the treatment as front-line (enrolled in the GOLFIG-2 phase III trial) and 117 as second/third line (49 enrolled in the GOLFIG-1 phase II trial and 68 as compassionate use). One-hundred twelve patients showed a primary left side and 67 a primary right side; K/N-ras mutational status was available in 74 cases and an activating mutation was detected in 33. Kaplan-Meier and Cox-regression analyses were carried out to relate PFS and OS with different parameters.
Results: On the overall, we recorded a mean PFS and OS of 15.28 [95%CI:10,36-20,20] and 24.6 [95%CI:19,07-30,14] months, respectively, with 14 patients surviving free of progression for ten years. This regimen, in our updated survey of the GOLFIG-2 trial, confirmed superiority over FOLFOX in term of PFS (HR= 0.58 p=0.006) with a trend to a longer OS (HR=0.69, P=0.06) in the first line. Our analysis also confirmed significant antitumor activity in pre-treated patients reporting a mean PFS and OS of 12.55 [95%CI:7.19-17.9] and 20.28 [95%CI:14.4-26.13] months, respectively. IrAEs were recorded in 24% of the cases and were related to a longer survival (HR=0.36; P=0.0001). Finally, patients’ outcome was not correlated to sex, sidedness and MT-K/N-ras.
Conclusions: GOLFIG regimen is a reliable underestimated therapeutic option in pre-treated mCRC patients and offers a strong rationale to design further trials.

Keywords: colorectal cancer, Metastatic, chemotherapy, Immunotherapy, Phase III clinical trial, real world medicine, GOLFIC

Received: 21 Jul 2019; Accepted: 07 Oct 2019.

Copyright: © 2019 Caraglia, Correale, Giannicola, Staropoli, Botta, Pastina, Nesci, Caporlingua, Francini, Ridolfi, Mini, Roviello, Ciliberto, Agostino, Strangio, Azzarello, NARDONE, Falzea, Cappabianca, Bocchetti, D’Arrigo, Tripepi, Tassone, Addeo, Giordano, Pirtoli, Francini and Tagliaferri. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Michele Caraglia, University of Campania Luigi Vanvitelli, Caserta, Italy, michele.caraglia@unicampania.it
Dr. Pierpaolo Correale, Department on Oncology, Hematology and Radiotherapy, Bianchi-Melacrino-Morelli Hospital of Reggio Calabria, Reggio Calabria, Italy, correalep@yahoo.it
Dr. Nicoletta Staropoli, Department of Clinical and Experimental Medicina, University of Magna Græcia di Catanzaro studios, Catanzaro, Italy, staropoli@unicz.it