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FOLFIRINOX: A Great Leap Forward, but for Whom?

In his report, Ko1 briefly discusses the influence of ethnical factors in toxicity.

Journal of Clinical Oncology – JCO

To the Editor

Journal of Clinical Oncology published an article by Ko1 in the Comments and Controversies section. We do believe FOLFIRINOX (biweekly bolus plus infusional fluorouracil, leucovorin, irinotecan, and oxaliplatin) is a major step forward for patients with pancreatic cancer, and it must be considered the new backbone for clinical practice and also for therapy development.2

In his report, Ko1 briefly discusses the influence of ethnical factors in toxicity. Several factors related to the patient as well as tumor biology can greatly interfere with the clinical outcomes of those with pancreatic cancer. A better understanding of these predictors of efficacy and toxicity must be extensively pursued. For example, human equilibrative nucleoside transporter 1 (hENT1) is a predictor of response and survival for patients with pancreatic cancer treated with gemcitabine in different settings.3–6 Perhaps for patients whose tumors express high levels of hENT1, the benefit of FOLFIRINOX over gemcitabine would not be clinically meaningful, therefore allowing us to continue offering such patients gemcitabine-based therapy, which has a better toxicity profile without compromising efficacy. Recently, Paproski et al7 evaluated a new positron emission tomography tracer (ie, 30-deoxy-30-fluorothymidine), which would be a good substitute for hENT1 immunohistochemistry in pancreatic cancer. If these assumptions were real, a noninvasive procedure would be worthy for selecting patients for a certain chemotherapy regimen.

There are several other markers predicting clinical outcomes to gemcitabine, fluoropyrimidines, camptothecins, and platinum compounds in other diseases and settings, and these should be evaluated in the changing landscape of individualized care for pancreatic cancer.


Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a “U” are those for which no compensation was received; those relationships marked with a “C” were compensated. For a detailed description of the disclosure categories, or for more information about ASCO’s conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

Employment or Leadership Position: None Consultant or Advisory Role: None Stock Ownership: None Honoraria: None Research Funding: Lucas Vieira dos Santos, ImClone Systems Expert Testimony: None Other Remuneration: None


1- Ko AH (2011) FOLFIRINOX: A small step or a great leap forward? J Clin Oncol 29:3727–3729. FREE Full Text
2 -Conroy T, Desseigne F, Ychou M, et al. (2011) FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364:1817–1825. CrossRefMedline
3- Farrell JJ, Elsaleh H, Garcia M, et al. (2009) Human equilibrative nucleoside transporter 1 levels predict response to gemcitabine in patients with pancreatic cancer. Gastroenterology 136:187–195. CrossRefMedline
4- Giovannetti E, Del Tacca M, Mey V, et al. (2006) Transcription analysis of human equilibrative nucleoside transporter-1 predicts survival in pancreas cancer patients treated with gemcitabine. Cancer Res 66:3928–3935. Abstract/FREE Full Text
5- Maréchal R, Mackey JR, Lai R, et al. (2009) Human equilibrative nucleoside transporter 1 and human concentrative nucleoside transporter 3 predict survival after adjuvant gemcitabine therapy in resected pancreatic adenocarcinoma. Clin Cancer Res 15:2913–2919. Abstract/FREE Full Text
6- Spratlin J, Sangha R, Glubrecht D, et al. (2004) The absence of human equilibrative nucleoside transporter 1 is associated with reduced survival in patients with gemcitabine-treated pancreas adenocarcinoma. Clin Cancer Res 10:6956–6961. Abstract/FREE Full Text
7- Paproski RJ, Young JD, Cass CE (2010) Predicting gemcitabine transport and toxicity in human pancreatic cancer cell lines with the positron emission tomography tracer 3′-deoxy-3′-fluorothymidine. Biochem Pharmacol 79:587–595. CrossRefMedline

Autores: Lucas Vieira dos Santos, Diocésio Pinto de Andrade and João Paulo Lima


Responsáveis técnicos:
Dr. Diocésio Alves Pinto de Andrade | CRM-SP: 132129
Dr. Bruno Lemos Ferrari | CRM-MG: 26609