Background Cisplatin-based chemotherapy is frequently used to treat advanced gastric cancer (GC). Although it leads to increased overall survival (OS) when added to single agents or chemotherapy doublets, toxicity is also generally increased. The purpose of this meta-analysis study was to compare the efficacy of fchemotherapy with and without cisplatin in patients with advanced GC. Methods Randomised trials that compared first-line cisplatin-based chemotherapy with regimens in which cisplatin was replaced by other agents were identified by electronic searches of PubMed, EMBASE, the Web of Science, and the Cochrane Central Register of Controlled Trials. Meta-analysis was performed using a fixed or random effects model. OS, reported as a hazard ratio (HR) and a 95% confidence interval (CI), was the primary outcome measure. Results Fourteen trials (5 phase III and 9 phase II), including 2,981 patients, were identified. Overall, chemotherapy regimens without cisplatin significantly improved OS (HR, 0.79; 95% CI, 0.68–0.92; p = 0.003), progression-free survival (PFS) (HR, 0.77; 95% CI, 0.66–0.90; p = 0.001), and response rate (RR) (OR, 1.25; p = 0.004) when compared to cisplatin-containing regimens. A subgroup analysis according to histology, site of the primary tumour and extent of disease was not possible due to lack of data. Conclusions Compared with cisplatin-based doublets and triplets, combinations in which cisplatin was replaced by new drugs improved outcome and RRs in randomised trials for advanced GC and therefore should be strongly considered in the metastatic setting. A limitation of this meta-analysis is that we cannot identify a subgroup of patients (according to histology, site of primary tumour or burden of metastatic disease) which could derive greater benefit from cisplatin-free chemotherapy.
References
[1]
Wagner AD, Unverzagt S, Grothe W, Kleber G, Grothey A, et al. (2010) Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev. Mar 17 (3): CD004064 doi: 10.1002/14651858.CD004064.pub3.
[2]
The GASTRIC (Global Advanced/Adjuvant Stomach Tumor Research International Collaboration) Group, Oba K, Paoletti X, Bang YJ, Bleiberg H, et al (2013) Role of chemotherapy for advanced/recurrent gastric cancer: An individual-patient-data meta-analysis. Eur J Cancer 49(7): 1565–1577.
[3]
Montagnani F, Turrisi G, Marinozzi C, Aliberti C, Fiorentini G (2011) Effectiveness and safety of oxaliplatin compared to cisplatin for advanced, unresectable gastric cancer: a systematic review and meta-analysis. Gastric Cancer 14(1): 50–5.
[4]
Qi WX, Shen Z, Lin F, Sun YJ, Min DL, et al. (2013) Overall survival benefits for irinotecan-containing regimens as first-line treatment for advanced gastric cancer: an updated meta-analysis of ten randomized controlled trials. Int J Cancer 132(2): E66–73.
[5]
Dank M, Zaluski J, Barone C, Valvere V, Yalcin S, et al. (2008) Randomized phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 19(8): 1450–1457.
[6]
Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, et al. (2008) Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 358(1): 36–46.
[7]
Seng S, Liu Z, Chiu SK, Proverbs-Singh T, Sonpavde G, et al. (2012) Risk of venous thromboembolism in patients with cancer treated with Cisplatin: a systematic review and meta-analysis. J Clin Oncol. 30(35): 4416–4426.
[8]
Cassidy J, Saltz L, Twelves C, Van Cutsem E, Hoff P, et al. (2011) Efficacy of capecitabine versus 5-fluorouracil in colorectal and gastric cancers: a meta-analysis of individual data from 6171 patients. Ann Oncol. 22(12): 2604–2609.
[9]
Huang J, Cao Y, Wu L, Liao C, He Y, et al. (2011) S-1-based therapy versus 5-FU-based therapy in advanced gastric cancer: a meta-analysis. Med Oncol 28(4): 1004–1011.
[10]
Roth AD, Fazio N, Stupp R, Falk S, Bernhard J, et al. (2007) Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol 25(22): 3217–3223.
[11]
Parmar MK, Torri V, Stewart S (1998) Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Statistics in Medicine 17: 2815–2834.
[12]
Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR (2007) Practical methods for incorporating summary time-to-event data into meta-analysis. Trials 8: 16.
[13]
Williamson P, Tudur Smith C, Hutton JL, Marson AG (2002) Aggregrate data meta-analysis with time-to-event outcomes. Statistics in Medicine 21: 3337–3351.
[14]
Mochiki E, Ogata K, Ohno T, Toyomasu Y, Haga N, et al. (2012) Phase II multi-institutional prospective randomised trial comparing S-1+paclitaxel with S-1+cisplatin in patients with unresectable and/or recurrent advanced gastric cancer. Br J Cancer 107(1): 31–36.
[15]
Jeung HC, Rha SY, Im CK, Shin SJ, Ahn JB, et al. (2011) A randomized phase 2 study of docetaxel and S-1 versus docetaxel and cisplatin in advanced gastric cancer with an evaluation of SPARC expression for personalized therapy. Cancer 117(10): 2050–2057.
[16]
Moehler M, Kanzler S, Geissler M, Raedle J, Ebert MP, et al. (2010) A randomized multicenter phase II study comparing capecitabine with irinotecan or cisplatin in metastatic adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol 21(1): 71–77.
[17]
Popov I, Radosevic-Jelic L, Jezdic S, Milovic M, Borojevic N, et al. (2008) Biweekly oxaliplatin, fluorouracil and leucovorin versus cisplatin, fluorouracil and leucovorin in patients with advanced gastric cancer. J BUON 13(4): 505–511.
[18]
Al-Batran SE, Hartmann JT, Probst S, Schmalenberg H, Hollerbach S, et al. (2008) Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol 26(9): 1435–1442.
[19]
Pozzo C, Barone C, Szanto J, Padi E, Peschel C, et al. (2004) Irinotecan in combination with 5-fluorouracil and folinic acid or with cisplatin in patients with advanced gastric or esophageal-gastric junction adenocarcinoma: results of a randomized phase II study. Ann Oncol 15(12): 1773–1781.
[20]
Bouché O, Raoul JL, Bonnetain F, Giovannini M, Etienne PL, et al. (2004) Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: a Federation Francophone de Cancerologie Digestive Group Study – FFCD 9803. J Clin Oncol 22(21): 4319–4328.
[21]
Ikeda R, Yoshida K, Satou Y, Takahashi Y, Une W, et al. (2009) Randomized phase II/III study of docetaxel/S-1 (DS-1) versus CDDP/5FU (FUP) in advanced or recurrent gastric cancer: Updated phase II results. J Clin Oncol 27: 15s (suppl abstr 4595)..
[22]
Sym S, Park S, Kwon K, Jung J, Park E, et al. (2009) A randomized phase II trial of weekly docetaxel plus either cisplatin or oxaliplatin in patients with previously untreated advanced gastric cancer: Preliminary results. J Clin Oncol 27: 15s (suppl abstr 4566)..
[23]
Elsaid AA, Elkem Y (2005) Final results of a randomized phase III trial of Docetaxel, Carboplatin and 5FU versus Epirubicin, cisplatin and 5FU for locally advanced gastric cancer. J Clin Oncol 23: 16s, abstr 4014.
[24]
Tesselaar ME, Luelmo S, Polee M, van Bochove A, Ouwerkerk J, et al.. (2008) Randomized, phase II study comparing cisplatin and high-dose 5-fluorouracil/leucovorin with paclitaxel and high-dose 5-fluorouracil/leucovorin in patients with advanced gastric cancer and adenocarcinomas of the gastroesophageal junction. J Clin Oncol 26 (May 20 suppl abstr 4567).
[25]
Higuchi K, Koizumi W, Yamada Y, Nishikawa K, Gotoh M, et al.. (2012) Randomized phase III study of S-1 plus oxaliplatin versus S-1 plus cisplatin for first-line treatment of advanced gastric cancer. J Clin Oncol 30: (suppl 34, abstr 60).
[26]
Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, et al. (2010) Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 376(9742): 687-697. Erratum in: Lancet 376(9749): 1302.
[27]
Hegewisch-Becker S, Moorahrend E, Kr？ning H, Petersen V, Hannig C, et al.. (2012) Trastuzumab (TRA) in combination with different first-line chemotherapies for treatment of HER2-positive metastatic gastric or gastroesophageal junction cancer (MGC): Findings from the German noninterventional observational study HerMES. J Clin Oncol 30 (suppl abstr 4065).
[28]
Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, et al. (2012) Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet 379(9813): 315–321.
