Lay Summary: GemOX is an active regimen for pancreatic cancer.
Locally advanced and metastatic pancreatic adenocarcinomas carry a very poor prognosis. In patients treated with the standard palliative treatment gemcitabine (GEM), median survival still remains only 6 months. Over the last several years, many trials have been designed combining GEM with various other drugs to treat chemo-naive patients, with the aim to improve overall survival. Unfortunately, none of the GEM-based combinations studied so far have reached that objective, with the exception of GEM plus Erlotinib, which showed a slight increase in OS to 6.4 months. However, some trials – mainly those using platinum based combinations – have shown an increase in response rate and time to progression.
The combination of GEM and oxaliplatin (GEMOX regimen) has been reported by Louvet et al, to be active in first-line therapy against advanced and metastatic pancreatic cancer. GEMOX has also been shown to provide significantly better RR, clinical benefit response (CBR) and period-free survival (PFS) than GEM alone. Furthermore, toxicity with this combination is limited.
The GEMOX combination was shown to have a survival benefit of an additional 2 months, but this difference was not significant. Possible causes of this could be the lack of power in the statistical assumption, the inclusion of a high number of locally advanced diseases (LAD), and the proportion of second-line therapy using a platinum-based regimen. A recent metanalusis suggested that GemOx prolongs survival, which none of the individual trials showed.
However, there are still no guidelines or recommendations for selecting treatment for patients progressing after GEM therapy; nor are there any reports of regimens with demonstrated activity that would enable one to justify one approach over another. 2010 NCCN does not list gemcitabine oxaliplatin although it lists gemcitabine cisplatin.
There is on ongoing study that is no longer recruting: Gemcitabine With or Without Oxaliplatin in Treating Patients With Locally Advanced or Metastatic Unresectable Pancreatic Adenocarcinoma, NCT00075452. NCCN lists a study of CapOx, versus GemOx and GemCapOx and mentions interim findings on p. 41 but also taht the study is ongoing.
A Demols et al,Gemcitabine and oxaliplatin (GEMOX) in gemcitabine refractory advanced pancreatic adenocarcinoma: a phase II study, British Journal of Cancer (2006) 94, 481-485.
Louvet C, André T, Lledo G, Hammel P, Bleiberg H, Bouleuc C, Gamelin E, Flesch M, Cvitkovic E, de Gramont A (2002) Gemcitabine combined with oxaliplatin in advanced pancreatic adenocarcinoma: final results of a GERCOR multicenter phase II study. J Clin Oncol 20(6): 1512–1518
Louvet C, Labianca R, Hammel P, Lledo G, Zampino MG, Andre T, Zaniboni A, Ducreux M, Aitini E, Taieb J, Faroux R, Lepere C, de Gramont A (2005) Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol 23(15): 3509
H. Q. Xiong, R. A. Wolff, K. R. Hess, G. R. Varadhachary, J. C. Blaisand J. L. Abbruzzese A phase II trial of oxaliplatin plus capecitabine (xelox) as second line therapy for patients with advanced pancreatic cancer Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 24, No 18S (June 20 Supplement), 2006: 4119
FOLFOX-6 Combination in the First-Line Treatment of Locally Advanced and/or Metastatic Pancreatic Cancer. ASCO 2006, Abstract 106]