Management of Advanced Pancreatic Cancer with Gemcitabine Plus Erlotinib: Efficacy and Safety Results in Clinical Practice

  • Robert Diaz Beveridge Department of Medical Oncology, University Hospital La Fe. Valencia, Spain
  • Vicent Alcolea Department of Medical Oncology, University Hospital La Fe. Valencia, Spain
  • Jorge Aparicio Department of Medical Oncology, University Hospital La Fe. Valencia, Spain
  • Ángel Segura Department of Medical Oncology, University Hospital La Fe. Valencia, Spain
  • Jose García Department of Medical Oncology, University Hospital La Fe. Valencia, Spain
  • Miguel Corbellas Department of Medical Oncology, University Hospital La Fe. Valencia, Spain
  • María Fonfría Department of Medical Oncology, University Hospital La Fe. Valencia, Spain
  • Alejandra Giménez Department of Medical Oncology, University Hospital La Fe. Valencia, Spain
  • Joaquin Montalar Department of Medical Oncology, University Hospital La Fe. Valencia, Spain
Keywords: erlotinib, gemcitabine, Pancreatic Neoplasms

Abstract

Context The combination of gemcitabine and erlotinib is a standard first-line treatment for unresectable, locally advanced or metastatic pancreatic cancer. We reviewed our single centre experience to assess its efficacy and toxicity in clinical practice. Methods Clinical records of patients with unresectable, locally advanced or metastatic pancreatic cancer who were treated with the combination of gemcitabine and erlotinib were reviewed. Main outcome measures Univariate survival analysis and multivariate analysis were carried out to indentify independent predictors factors of overall survival. Results Our series included 55 patients. Overall disease control rate was 47%: 5% of patients presented complete response, 20% partial response and 22% stable disease. Median overall survival was 8.3 months). Cox regression analysis indicated that performance status and locally advanced versus metastatic disease were independent factors of overall survival. Patients who developed acne-like rash toxicity, related to erlotinib administration, presented a higher survival than those patients who did not develop this toxicity. Conclusions Gemcitabine plus erlotinib doublet is active in our series of patients with advanced pancreatic cancer. This study provides efficacy and safety results similar to those of the pivotal phase III clinical trial that tested the same combination.

Image: Overall survival and development of acne-like rash.

Downloads

Download data is not yet available.

References

Burris HA, Moore MJ, Andersen J Green MR, Rothenberg ML, Modiano MR, et al. Improvements in survival and clinical benefit with gemcitabine as first line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 1997; 15:2403-13

Poplin E, Feng Y, Berlin J, Rothenberg ML, Hochster H, Mitchell E, et al. Phase III randomized study of gemcitabine and oxaliplatin versus gemcitabine (fixed-dose-rate-infusion) compared with gemcitabine (30-min infusion) in patients with pancreatic carcinoma. E6201: a trial of ECOG. J Clin Oncol 2009; 27:3778-85.

Herrmann R, Bodoky G, Ruhstaller T, Glimelius B, Bajetta E, Schüller J, et al; Swiss Group for Clinical Cancer Research; Central European Cooperative Oncology Group. Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer: a randomized, multicenter, phase III trial of the Swiss Group for Clinical Cancer Research and the Central ECOG. J Clin Oncol 2007; 25:2212-7.

Colucci G, Giuliani F, Gebbia V, Biglietto M, Rabitti P, Uomo G, et al. Gemcitabine alone or with cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma: a prospective, randomized, phase III study of the Gruppo Oncologia dell’Italia Meridionale. Cancer 2002; 94:902-10.

Fine RL, Fogelman DR, Schreibman SR, Desai M, Sherman W, Strauss J, et al. The gemcitabine, docetaxel and capecitabine (GTX) regimen for metastatic pancreatic cancer: a retrospective analysis. Cancer Chemother Pharmacol 2008; 61:167-75.

Reni M, Cordio S, Milandri C, Passoni P, Bonetto E, Oliani C, et al. Gemcitabine versus cisplatin, epirubicin, fluorouracil and gemcitabine in advanced pancreatic cancer: a randomized controlled multicentre phase III trial. Lancet Oncol 2005; 6:369-76.

Kindler HL, Friberg G, Singh DA, Locker G, Nattam S, Kozloff M, et al. Phase II trial of bevacizumab plus gemcitabine in patients with advanced pancreatic cancer. J Clin Oncol 2005; 23:8033-40.

Xiong HQ, Rosenberg A, LoBuglio A Schmidt W, Wolff RA, Deutsch J, et al. Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, in combination with gemcitabine for advanced pancreatic cancer: a multicenter phase II Trial. J Clin Oncol 2004; 22:2610-6.

Kindler HL, Niedzwiecki D, Hollis D, Oraefo E, Schrag D, Hurwitz H, et al. A double-blind placebo-controlled, randomized phase III trial of gemcitabine (G) plus bevacizumab (B) versus gemcitabine plus placebo (P) in patients (pts) with advanced pancreatic cancer (PC): A preliminary analysis of Cancer and Leukemia Group B (CALGB) 80303. Presented at: 2007 ASCO Gastrointestinal Cancers Symposium; January 17-21, 2007; Orlando, Florida. Abstract 108.

Lemoine NR, Hughes CM, Barton CM, Poulsom R, Jeffery RE, Klöppel G, et al. The epidermal growth factor receptor in human pancreatic cancer. J Pathol 1992;166:7-12.

Tzeng CW, Frolov A, Frolova N, Jhala NC, Howard JH, Vickers SM, et al. EGFR genomic gain and aberrant pathway signaling in pancreatic cancer patients. J Surg Res 2007; 143:20-6.

Fujita H, Ohuchida K, Mizumoto K, Itaba S, Ito T, Nakata K, et al. High EGFR mRNA expression is a prognostic factor for reduced survival in pancreatic cancer after gemcitabine-based adjuvant chemotherapy. Int J Oncol 2011; 38:629-41.

Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, et al.; National Cancer Institute of Canada Clinical Trials Group. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 2007; 25:1960-6.

Xiong HQ. Molecular targeting therapy for pancreatic cancer. Cancer Chemother Pharmacol 2004; 54:S69-77.

Ueda S, Ogata S, Tsuda H, Kawarabayashi N, Kimura M, Sugiura Y, et al. The correlation between cytoplasmic overexpression of epidermal growth factor receptor and tumor aggressiveness: poor prognosis in patients with pancreatic ductal adenocarcinoma. Pancreas 2004; 29:1-8.

Furukawa T. Molecular pathology of pancreatic cancer: implications for molecular targeting therapy. Clin Gastroenterol Hepatol 2009; 7:35-9.

Schlieman MG, Fahy BN, Ramsamooj R, Beckett L, Bold RJ. Incidence, mechanism and prognostic value of activated AKT in pancreas cancer. Br J Cancer 2003; 89:2110-5.

Asano T, Yao Y, Zhu J, Li D, Abbruzzese JL, Reddy SA. The PI-3-kinase/Akt signaling pathway is activated due to aberrant PTEN expression and targets transcription factors NF-kB and c-myc in pancreatic cancer cells. Oncogene 2004; 23:8571-80.

Korc M. Pathways for aberrant angiogenesis in pancreatic cancer. Mol Cancer 2003; 2:8.

Karayiannakis AJ, Bolanaki H, Syrigos KN, Asimakopoulos B, Polychronidis A, Anagnostoulis S, et al. Serum vascular endothelial growth factor levels in pancreatic cancer patients correlate with advanced and metastatic disease and poor prognosis. Cancer Lett 2003; 194:119-24.

Aranda E, Manzano JL, Rivera F, Galán M, Valladares-Ayerbes M, Pericay C, et al. Phase II open-label study of erlotinib in combination with gemcitabine in unresectable and/or metastatic adenocarcinoma of the pancreas: relationship between skin rash and survival (Pantar study). Ann Oncol 2012; 23:1919-25.

Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, et al.; Groupe Tumeurs Digestives of Unicancer; PRODIGE Intergroup. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011; 364:1817-25.

Overall survival and development of acne-like rash
Published
2014-01-10
How to Cite
Diaz BeveridgeR., AlcoleaV., AparicioJ., Segura Ángel, GarcíaJ., CorbellasM., FonfríaM., GiménezA., & MontalarJ. (2014). Management of Advanced Pancreatic Cancer with Gemcitabine Plus Erlotinib: Efficacy and Safety Results in Clinical Practice. JOP. Journal of the Pancreas, 15(1), 19-24. https://doi.org/10.6092/1590-8577/1570
Section
ORIGINAL ARTICLES