title: Gastric cancer: toward a cisplatin-free disease?
abstract: Historically, the cornerstone of treatment of advanced gastric cancer (GC) is 5-fluorouracil (5-FU)-based chemotherapy that increases median overall survival (OS) compared to best supportive care by some months. The addition of cisplatin (CDDP) to chemotherapy doublets showed a limited but significant benefit in term of OS according to a Cochrane meta-analysis. However, the recent individual patient-data GASTRIC meta-analysis, confirms this benefit in term of progression-free survival (PFS) but not OS, in randomized eight trials that include or not CDDP. The substitution of CDDP with a modern agent (oxaliplatin, irinotecan or taxanes) has been poorly evaluated in the literature. The REAL-2 phase III trial confirmed the equivalence of oxaliplatin and CDDP-based triplets, and a meta-analysis of three oxaliplatin-based randomized trials demonstrated that these combinations are better that CDDP-based doublets or triplets, improving both PFS (HR =0.88) and OS (HR =0.88). In particular, oxaliplatin-based chemotherapy was associated with less neutropenia and thromboembolic events, but with worse neurotoxicity. Given that the role of chemotherapy in advanced GC is palliative, CDDP-free regimens, and in particular oxaliplatin-based chemotherapy, may be considered for both CDDP-fit and unfit patients (that are those with poor renal function, older age, bad performance status or who cannot tolerate forced hydration for example). The limited absolute survival benefit of chemotherapy in advanced GC (few weeks at best), the cumbersome vascular toxicity of CDDP and the activity of several new drugs such irinotecan, oxaliplatin, taxanes and oral fluoropyrimidines make nowadays possible to consider CDDP-free regimens for the treatment of this incurable disease.
authors.affiliation: 1 Oncology Department, Medical Oncology Unit, Azienda Ospedaliera Treviglio, Treviglio (BG), Italy ; 2 Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, Ancona, Italy ; 3 UO Oncologia, Dipartimento Oncologico, Istituto Ospedaliero Fondazione Poliambulanza, Brescia, Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Petrelli
authors.affiliation: 1 Oncology Department, Medical Oncology Unit, Azienda Ospedaliera Treviglio, Treviglio (BG), Italy ; 2 Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, Ancona, Italy ; 3 UO Oncologia, Dipartimento Oncologico, Istituto Ospedaliero Fondazione Poliambulanza, Brescia, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Barni
authors.affiliation: 1 Oncology Department, Medical Oncology Unit, Azienda Ospedaliera Treviglio, Treviglio (BG), Italy ; 2 Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, Ancona, Italy ; 3 UO Oncologia, Dipartimento Oncologico, Istituto Ospedaliero Fondazione Poliambulanza, Brescia, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
authors.affiliation: 1 Oncology Department, Medical Oncology Unit, Azienda Ospedaliera Treviglio, Treviglio (BG), Italy ; 2 Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, Ancona, Italy ; 3 UO Oncologia, Dipartimento Oncologico, Istituto Ospedaliero Fondazione Poliambulanza, Brescia, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Zaniboni
keywords: Cisplatin (CDDP); first line; gastric cancer (GC); overall survival (OS); oxaliplatin; toxicity
references.citation: Ann Oncol. 1997 Feb;8(2):163-8
references.pmid: 9093725
references.citation: Gastric Cancer. 2011 Mar;14(1):50-5
references.pmid: 21340667
references.citation: J Clin Oncol. 2006 Jun 20;24(18):2903-9
references.pmid: 16782930
references.citation: Eur J Cancer. 2013 May;49(7):1565-77
references.pmid: 23352439
references.citation: Cochrane Database Syst Rev. 2010 Mar 17;(3):CD004064
references.pmid: 20238327
references.citation: Onkologie. 2011;34(10):548-51
references.pmid: 21985855
references.citation: Ann Oncol. 2015 Jan;26(1):149-156
references.pmid: 25416687
references.citation: N Engl J Med. 2008 Jan 3;358(1):36-46
references.pmid: 18172173
references.citation: Br J Cancer. 1995 Mar;71(3):587-91
references.pmid: 7533517
references.citation: N Engl J Med. 2006 Jul 6;355(1):11-20
references.pmid: 16822992
references.citation: Lancet. 2012 Jan 28;379(9813):315-21
references.pmid: 22226517
references.citation: PLoS One. 2013 Dec 27;8(12):e83022
references.pmid: 24386137
references.citation: J Clin Oncol. 1997 Jan;15(1):261-7
references.pmid: 8996151
references.citation: Lancet. 2010 Aug 28;376(9742):687-97
references.pmid: 20728210
references.citation: Anticancer Res. 2008 Jul-Aug;28(4B):2087-92
references.pmid: 18751380
references.citation: Cancer. 1993 Jul 1;72(1):37-41
references.pmid: 8508427
references.citation: J Clin Oncol. 2016 Aug 10;34(23):2736-42
references.pmid: 27382098
references.citation: J Clin Oncol. 2000 Jul;18(14):2648-57
references.pmid: 10894863
references.citation: J Natl Cancer Inst. 2004 May 19;96(10):739-49
references.pmid: 15150302
references.citation: Onkologie. 2012;35(9):505-8
references.pmid: 23007148
references.citation: J Clin Oncol. 2012 Dec 10;30(35):4416-26
references.pmid: 23150697
references.citation: N Engl J Med. 2001 Mar 15;344(11):783-92
references.pmid: 11248153
references.citation: Int J Cancer. 2013 Jan 15;132(2):E66-73
references.pmid: 22890856
references.citation: JAMA. 2010 May 5;303(17):1729-37
references.pmid: 20442389