Array ( [0] => {{Short description|Chemotherapy regimen}} [1] => {{Use dmy dates|date=March 2022}} [2] => '''FOLFIRINOX''' is a [[chemotherapy regimen]] for treatment of advanced [[pancreatic cancer]]. It is made up of the following four drugs: [3] => [4] => * FOL – [[folinic acid]] (leucovorin), a vitamin B derivative that enhances the effects of 5-fluorouracil (5-FU);{{cite journal |pmid = 2963229|year = 1987|last1 = Moran|first1 = R. G.|last2 = Keyomarsi|first2 = K.|title = Biochemical rationale for the synergism of 5-fluorouracil and folinic acid|journal = NCI Monographs |issue = 5|pages = 159–63}}{{cite web |url=https://www.drugbank.ca/drugs/DB00650|title=Leucovorin}} [5] => * F – [[fluorouracil]] (5-FU), a [[pyrimidine analog]] and [[antimetabolite]] which incorporates into the DNA molecule and stops [[DNA synthesis]]; [6] => * IRIN – [[irinotecan]] (Camptosar), a [[topoisomerase]] inhibitor, which prevents DNA from uncoiling and duplicating; and [7] => * OX – [[oxaliplatin]] (Eloxatin), a [[platinum-based antineoplastic]] agent, which inhibits [[DNA repair]] and/or DNA synthesis. [8] => [9] => The regimen emerged in 2010 as a new treatment for patients with [[metastatic]] pancreatic cancer.{{cite journal |last1=Conroy |first1=T |last2=Gavoille |first2=C |last3=Samalin |first3=E |last4=Ychou |first4=M |last5=Ducreux |first5=M |title=The role of the FOLFIRINOX regimen for advanced pancreatic cancer |journal=Current Oncology Reports |year=2013 |volume=15 |issue=2 |pages=182–189 |doi=10.1007/s11912-012-0290-4 |pmid=23341367|s2cid=36317669 }}{{cite journal |last1=Faris |first1=JE |last2=Blaszkowsky |first2=LS |last3=McDermott |first3=S |title=FOLFIRINOX in locally advanced pancreatic cancer: the Massachusetts General Hospital Cancer Center experience |journal=Oncologist |year=2013 |volume=18 |issue=5 |pages=543–548 |doi=10.1634/theoncologist.2012-0435 |pmid=23657686 |pmc=3662845|display-authors=etal}}{{cite web |title=FOLFIRINOX |publisher=Pancreatic Cancer Association |url=http://pancreaticcanceraction.org/pancreatic-cancer/treatment/chemotherapy/chemotherapy-drugs-treat-cancer/folfirinox/ |accessdate=September 6, 2013 |url-status=dead |archiveurl=https://web.archive.org/web/20130917132346/http://pancreaticcanceraction.org/pancreatic-cancer/treatment/chemotherapy/chemotherapy-drugs-treat-cancer/folfirinox |archivedate=September 17, 2013 }} A 2011 study published in the ''New England Journal of Medicine'' found that FOLFIRINOX produced the longest improvement in survival ever seen in a phase III clinical trial of patients with advanced pancreatic cancer, with patients on the FOLFIRINOX treatment living approximately four months longer than patients receiving the standard [[gemcitabine]] treatment (11.1 months compared with 6.8 months).{{cite web |title=Chemotherapy Regimen Extends Survival in Advanced Pancreatic Cancer Patients |date=7 June 2011 |publisher=[[National Cancer Institute]] |url=http://www.cancer.gov/clinicaltrials/results/summary/2011/pancreatic-chemo0611 |accessdate=September 6, 2013}}{{cite journal |last1=Conroy |first1=T |last2=Desseigne |first2=F |last3=Ychou |first3=M |last4=et al, on behalf of Groupe Tumeurs Digestives of Unicancer, PRODIGE Intergroup |title=FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer |journal=[[New England Journal of Medicine]] |year=2011 |volume=364 |issue=19 |pages=1817–1825 |doi=10.1056/nejmoa1011923 |pmid=21561347|doi-access=free }} However, FOLFIRINOX is a potentially highly toxic combination of drugs with serious side effects, and only patients with good [[performance status]] are candidates for the regimen.{{cite journal|last1=Thota|first1=R|last2=Pauff|first2=JM|last3=Berlin|first3=JD|title=Treatment of metastatic pancreatic adenocarcinoma: a review.|journal=Oncology (Williston Park, N.Y.)|date=Jan 2014|volume=28|issue=1|pages=70–4|pmid=24683721}} Currently FOLFIRINOX is being used to downstage patients with "borderline and locally advanced" disease with the hope of rendering their tumors amenable to surgical resection.{{cite journal |last1=Michelakos |first1=T |last2=Pergolini |first2=I |last3=Castillo |first3=CF |last4=Honselmann |first4=KC |last5=Cai |first5=L |last6=Deshpande |first6=V |last7=Wo |first7=JY |last8=Ryan |first8=DP |last9=Allen |first9=JN |last10=Blaszkowsky |first10=LS |last11=Clark |first11=JW |last12=Murphy |first12=JE |last13=Nipp |first13=RD |last14=Parikh |first14=A |last15=Qadan |first15=M |last16=Warshaw |first16=AL |last17=Hong |first17=TS |last18=Lillemoe |first18=KD |last19=Ferrone |first19=CR |title=Predictors of Resectability and Survival in Patients With Borderline and Locally Advanced Pancreatic Cancer who Underwent Neoadjuvant Treatment With FOLFIRINOX. |journal=Annals of Surgery |date=April 2019 |volume=269 |issue=4 |pages=733–740 |doi=10.1097/SLA.0000000000002600 |pmid=29227344|s2cid=206074649 }} [10] => [11] => In 2013, the U.S. [[Food and Drug Administration]] approved [[protein-bound paclitaxel]] (also known as nab-paclitaxel, sold as Abraxane) used with gemcitabine. This regimen may be less toxic—but perhaps less effective—alternative to FOLFIRINOX for treating late-stage pancreatic cancer. Differences in the trials, and the lack of a direct trial comparing the two regimens, preclude a final conclusion. In the United Kingdom, the [[National Institute for Health and Care Excellence]] (NICE), in a draft guidance issued in 2014, rejected the use of Abraxane in treatment due to concerns of side effects, efficacy, and cost relative to Gemzar ([[gemcitabine]]).{{cite press release |author= |title=The cost of nab-paclitaxel is not justified by its limited benefit, says NICE in draft guidance |url=https://www.nice.org.uk/news/press-and-media/the-cost-of-nab-paclitaxel-is-not-justified-by-its-limited-benefit-says-nice-in-draft-guidance-2 |publisher=National Institute for Health and Care Excellence |date=30 December 2014 |access-date=2022-03-29}} However, on 18 May 2017 NICE issued a reappraisal for the use of Abraxane in the UK. This was in response to [[Celgene]] putting forward a Patient Access Scheme (PAS) proposal, which would bring down the cost of the drug.{{cite press release |title=Pancreatic cancer patients to have routine access to life extending drug after new deal, says NICE |url=https://www.nice.org.uk/news/article/pancreatic-cancer-patients-to-have-routine-access-to-life-extending-drug-after-new-deal-says-nice |publisher=National Institute for Health and Care Excellence |date=4 August 2017 |access-date=8 March 2022}} [12] => [13] => ==See also== [14] => * [[FOLFIRI]] [15] => * [[FOLFOX]] [16] => * [[FOLFOXIRI]] [17] => * [[IFL (chemotherapy)|IFL]] [18] => [19] => ==References== [20] => {{reflist|30em}} [21] => [22] => [[Category:Chemotherapy regimens used in pancreatic cancer]] [] => )
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FOLFIRINOX

FOLFIRINOX is a chemotherapy regimen for treatment of advanced pancreatic cancer. It is made up of the following four drugs: * FOL - folinic acid (leucovorin), a vitamin B derivative that enhances the effects of 5-fluorouracil (5-FU); * F - fluorouracil (5-FU), a pyrimidine analog and antimetabolite which incorporates into the DNA molecule and stops DNA synthesis; * IRIN - irinotecan (Camptosar), a topoisomerase inhibitor, which prevents DNA from uncoiling and duplicating; and * OX - oxaliplatin (Eloxatin), a platinum-based antineoplastic agent, which inhibits DNA repair and/or DNA synthesis.

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Topoisomerase

DNA topoisomerases (or topoisomerases) are enzymes that catalyze changes in the topological state of DNA, interconverting relaxed and supercoiled forms, linked (catenated) and unlinked species, and knotted and unknotted DNA.