Epirubicin-cisplatin-5-fluorouracil (ECF) is commonly used to treat advanced gastric cancer. Two new cytotoxic agents: the platinum, oxaliplatin, and the oral fluoropyrimidine, capecitabine, have the potential to replace the cisplatin and 5-fluorouracil (5-FU) components of ECF, respectively. In this case, the regimen is capecitabine, Oxaliplatin and epirubicin.
Oxaliplatin combinations are now standard therapy for gastric cancer. Oxaliplatin based therapy is one of the options listed by NCCN for metastatic gastric cancer. The various oxaliplatin regimens in used has been extensively studied in Phase II; there are also studies with capecitabine and oxaliplatin. The 5FU.Leukovorin/oxaliplatin combination is approved by Cancer Care of Ontario which has issued evidence based recommendations and a guideline to support it (at http://www.cancercare.on.ca/pdf/pebc2-22s.pdf). Xeloda has been found able to substitute for 5FU in other cancer types. In the REAL-2 trial presented at ASCO 2006, the central research question was whether capecitabine, an oral pro-drug, could replace protracted venous infusion 5-FU, and whether oxaliplatin could replace cisplatin in the treatment of patients with advanced/non-resectable oesophago-gastric cancers. The use of capecitabine would remove the requirement for central venous access, and the potential line-related complications and morbidity therein. Moreover, oxaliplatin has a different toxicity profile to cisplatin, and is notably less nephro- and oto-toxic. The REAL-2 study of 1,002 patients with gastroesophageal cancer had a two-by-two factorial design, comprised four treatment arms with ECF as the reference arm and was designed to demonstrate non-inferiority of capecitabine over 5-FU, and oxaliplatin over cisplatin in the perprotocol population. Approximately 40% of patients had gastric cancer. There were no significant differences in quality of life between the arms.
Xelox with epirubicin in currenlty in a randomized phase II trial: Epirubicin, Oxaliplatin, and Capecitabine or Docetaxel and Oxaliplatin in Treating Patients With Advanced Esophageal Cancer, Gastroesophageal Junction Cancer, or Stomach Cancer,NCT00806949. Thus far, the only published study is an abstract from 2008 that concludes: “A combination of epirubicin, capecitabine and oxaliplatin every third week is a highly active and convenient regimen with a favourable safety profile.” However, also recently a four arm trial, one of which was the epirubicin, Xeloda and Oxaliplatin arm, showed equal efficacy with other standard arms.
NCCN has not incorporated this regimen but it does list Oxaliplatin with 5 floropyrimidines, not including epirubicin.
NCCN has not incorporated this regimen but it does list Oxaliplatin with 5 floropyrimidines, not including epirubicin. It also says in the SOPH-E, 1 and GAST-E,1 that Cisplatin can be exchanged with oxaliplatin and Xeloda with 5-FU, but says, however, that three drug regimens should be reserved for a medically fit adenocarcinoma patients with good performance status and ability to do frequent toxicity assessments. It, therefore, supports the Xeloda/oxaliplatin regimen.
For adjuvant chemotherapy:
From ESMO guideliens: “For patients with Stage IB gastric cancer who
have undergone surgery without administration of preoperative
chemotherapy (e.g. due to understaging before the initial decision
for upfront surgery), postoperative chemoradiotherapy (CRT) or
adjuvant chemotherapy is recommended [I, A]. F”.
NCCN on GAST-4 recommends 5FU based chemotherapy.
Cunningham, David, Starling, Naureen, Rao, Sheela, Iveson, Timothy, Nicolson, Marianne, Coxon, Fareeda, Middleton, Gary, Daniel, Francis, Oates, Jacqueline, Norman, Andrew Richard, the Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom,
Capecitabine and Oxaliplatin for Advanced Esophagogastric Cancer
N Engl J Med 2008 358: 36-46
Annamaria Ruzzo, Francesco Graziano, Kazuyuki Kawakami, Go Watanabe, Daniele Santini, Vincenzo Catalano, Renato Bisonni, Emanuele Canestrari, Rita Ficarelli, Ettore Tito Menichetti, Davide Mari, Enrica Testa, Rosarita Silva, Bruno Vincenzi, Paolo Giordani, Stefano Cascinu, Lucio Giustini, Giuseppe Tonini, Mauro Magnani Pharmacogenetic Profiling and Clinical Outcome of Patients With Advanced Gastric Cancer Treated With Palliative Chemotherapy Journal of Clinical Oncology, Vol 24, No 12 (April 20), 2006: pp. 1883-1891
Cunningham D, Rao S, Starling N, et al.,“Randomised multicentre phase III study comparing capecitabine with fluorouracil and oxaliplatin with cisplatin in patients with advanced oesophagogastric (OG) cancer:The REAL 2 trial”, J Clin Oncol 2006 ASCO Annual Meeting Proceedings (2006);24: Abstract LBA4017.
Gastric cancer: ESMO Clinical Practice Guidelines for
diagnosis, treatment and follow-up, Annals of Oncology 27 (Supplement 5): v38–v49, 2016
J. S. Macdonald Gastric cancer–new therapeutic options.
N. Engl. J. Med., July 6, 2006; 355(1): 76 – 77
M. H. Kulke The Treatment of Advanced Gastric Cancer: In Search of the Right Combination
J. Clin. Oncol., July 14, 2000; 18(14): 2645 – 2647.
C. Louvet, T. Andre, J.M. Tigaud, E. Gamelin, J.Y. Douillard, R. Brunet, E. Francois, J.H. Jacob, D. Levoir, A. Taamma, P. Rougier, E. Cvitkovic, and A. de Gramont Phase II Study of Oxaliplatin, Fluorouracil, and Folinic Acid in Locally Advanced or Metastatic Gastric Cancer Patients
J. Clin. Oncol., December 1, 2002; 20(23): 4543 – 4548
E. Al-Batran, A. Atmaca, S. Hegewisch-Becker, D. Jaeger, S. Hahnfeld, M. J Rummel, G. Seipelt, A. Rost, J. Orth, A. Knuth, and E. Jaeger
Phase II Trial of Biweekly Infusional Fluorouracil, Folinic Acid, and Oxaliplatin in Patients With Advanced Gastric Cancer
J. Clin. Oncol., February 15, 2004; 22(4): 658 – 663. 6
First-line EXE (epirubicin, capecitabine, and oxaliplatin) is a highly active and convenient out-patient regimen in patients with nonresectable gastric cancer.
2008 Gastrointestinal Cancers Symposium , 47