Procarbazine

{{Short description|Chemotherapy medication used for several cancer types}} {{Infobox drug | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 464214923 | IUPAC_name = ''N''-Isopropyl-4-[(2-methylhydrazino)methyl]benzamide | image = Procarbazine.svg | image_class = skin-invert-image | width = 180px | image2 = Procarbazine ball-and-stick.png | image_class2 = bg-transparent | width2 = 180px  | tradename = Matulane, Natulan, Indicarb, others | Drugs.com = {{drugs.com|monograph|procarbazine-hydrochloride}} | MedlinePlus = a682094 | pregnancy_AU = D | pregnancy_US = D | legal_status = Rx-only | routes_of_administration = By mouth (gel capsule), intravenous  | bioavailability = | metabolism = liver, kidney | elimination_half-life = 10 minutes | excretion = kidney  | IUPHAR_ligand = 7278 | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 671-16-9 | ATC_prefix = L01 | ATC_suffix = XB01 | PubChem = 4915 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB01168 | ChEBI_Ref = {{ebicite|changed|EBI}} | ChEBI = 71417 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 4746 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 35S93Y190K | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D08423 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 1321  | C=12 | H=19 | N=3 | O=1 | SMILES = O=C(c1ccc(cc1)CNNC)NC(C)C | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C12H19N3O/c1-9(2)15-12(16)11-6-4-10(5-7-11)8-14-13-3/h4-7,9,13-14H,8H2,1-3H3,(H,15,16) | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = CPTBDICYNRMXFX-UHFFFAOYSA-N }}  '''Procarbazine''' is a chemotherapy medication used for the treatment of Hodgkin lymphoma and brain cancers.<ref name=AHFS2016/> For Hodgkin lymphoma it is often used together with chlormethine, vincristine, and prednisone while for brain cancers such as glioblastoma multiforme it is used with lomustine and vincristine.<ref name=AHFS2016/> It is typically taken by mouth.<ref name=AHFS2016>{{cite web|title=Procarbazine Hydrochloride|url=https://www.drugs.com/monograph/procarbazine-hydrochloride.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161221013334/https://www.drugs.com/monograph/procarbazine-hydrochloride.html|archive-date=21 December 2016}}</ref>

Common side effect include low blood cell counts and vomiting.<ref name=AHFS2016/> Other side effects include tiredness and depression.<ref name=UKlabel2014>{{cite web|title=Procarbazine Capsules 50mg – Summary of Product Characteristics|url=https://www.medicines.org.uk/emc/medicine/386|publisher=UK Electronic Medicines Compendium|date=24 November 2014|url-status=live|archive-url=https://web.archive.org/web/20161220194931/https://www.medicines.org.uk/emc/medicine/386|archive-date=20 December 2016}}</ref><ref name=WHO2008>{{cite book | title = WHO Model Formulary 2008 | year = 2009 | isbn = 978-92-4-154765-9 | veditors = Stuart MC, Kouimtzi M, Hill SR | hdl = 10665/44053 | publisher = World Health Organization | hdl-access=free |page=228 }}</ref> It is not recommended in people with severe liver or kidney problems.<ref name=BNF69/> Use in pregnancy is known to harm the baby.<ref name=AHFS2016/> Procarbazine is in the alkylating agents family of medication.<ref name=AHFS2016/> How it works is not clearly known.<ref name=AHFS2016/>

Procarbazine was approved for medical use in the United States in 1969.<ref name=AHFS2016/> It is on the World Health Organization's List of Essential Medicines.<ref name="WHO21st">{{cite book | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref><ref name="WHO22nd">{{cite book | title = World Health Organization model list of essential medicines: 22nd list (2021) | year = 2021 | hdl = 10665/345533 | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2021.02 | hdl-access=free }}</ref> In the United Kingdom a month of treatment cost the National Health Service 450 to 750 pounds.<ref name=BNF69>{{cite book|title=British national formulary: BNF 69|date=2015|publisher=British Medical Association|isbn=978-0-85711-156-2|page=606|edition=69}}</ref>{{relevance inline|date=May 2025}}

==Medical uses== When used to treat Hodgkin lymphoma, it is often delivered as part of the BEACOPP regimen that includes bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine (tradename Oncovin), prednisone, and procarbazine. The first combination chemotherapy developed for Hodgkin lymphoma (HL), MOPP also included procarbazine (ABVD has supplanted MOPP as standard first line treatment for HL, with BEACOPP as an alternative for advanced/unfavorable HL). Alternatively, when used to treat certain brain tumors (malignant gliomas), it is often dosed as PCV when combined with lomustine (often called CCNU) and vincristine.

Dose is adjusted for kidney disease or liver disease.

==Side effects== Very common (greater than 10% of people experience them) adverse effects include loss of appetite, nausea and vomiting.<ref name=UKlabel2014/> Other side effects of unknown frequency include reduction in leukocytes, reduction in platelets, reduction in neutrophils, which can lead to increased infections including lung infections; severe allergy-like reactions that can lead to angioedema and skin reactions; lethargy; liver complications including jaundice and abnormal liver function tests; reproductive effects including reduction in sperm count and ovarian failure.<ref name=UKlabel2014/>

When combined with ethanol, procarbazine may cause a disulfiram-like reaction in some people.<ref name=UKlabel2014/>

It weakly inhibits MAO in the gastrointestinal system, so it can cause hypertensive crises if associated with the ingestion of tyramine-rich foods such as aged cheeses; this appears to be rare.<ref name=UKlabel2014/>

Procarbazine rarely causes chemotherapy-induced peripheral neuropathy,<ref>{{cite book | title = Holland-Frei Cancer Medicine | edition = 6th | chapter = Nonmetastatic Complications | vauthors = DeAngelis LM, Posner JS | veditors = Kufe DW, Pollock RE, Weichselbaum RR | location = Hamilton (ON) | publisher = BC Decker | date = 2003 | url = https://www.ncbi.nlm.nih.gov/books/NBK12946/ | display-editors = etal | url-status = live | archive-url = https://web.archive.org/web/20170911002308/https://www.ncbi.nlm.nih.gov/books/NBK12946/ | archive-date = 2017-09-11 }}</ref> a progressive, enduring, often irreversible tingling numbness, intense pain, and hypersensitivity to cold, beginning in the hands and feet and sometimes involving the arms and legs.<ref name=NCI>{{cite journal |vauthors=del Pino BM | date = Feb 23, 2010 | journal = NCI Cancer Bulletin | volume = 7 | issue = 4 | page = 6 | title = Chemotherapy-induced Peripheral Neuropathy | url = http://www.cancer.gov/aboutnci/ncicancerbulletin/archive/2010/022310/page6 |archive-url=https://web.archive.org/web/20111211105234/http://www.cancer.gov/aboutnci/ncicancerbulletin/archive/2010/022310/page6 |archive-date=2011-12-11}}</ref>

==Pharmacology== Procarbazine works, in part, as an alkylating agent and methylates guanine at the O-6 position (much like dacarbazine also does<ref name="pmid-20625128">{{cite journal | vauthors = Mauz-Körholz C, Hasenclever D, Dörffel W, Ruschke K, Pelz T, Voigt A, Stiefel M, Winkler M, Vilser C, Dieckmann K, Karlén J, Bergsträsser E, Fosså A, Mann G, Hummel M, Klapper W, Stein H, Vordermark D, Kluge R, Körholz D | display-authors = 6 | title = Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study | journal = Journal of Clinical Oncology | volume = 28 | issue = 23 | pages = 3680–3686 | date = August 2010 | pmid = 20625128 | doi = 10.1200/JCO.2009.26.9381 | doi-access = free }}</ref>). Guanine is one of the four nucleotides that makes up DNA. The methylated DNA is prone to breakage, and RNA and protein synthesis is inhibited.<ref>{{cite book | vauthors = Newton H |title=Handbook of Brain Tumor Chemotherapy |date=2006 |publisher=Academic Press |isbn=978-0-12-088410-0 |url=https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/procarbazine |access-date=1 January 2021}}</ref> Proliferating cancer cells need to replicate their DNA and undergo programmed cell death (apoptosis) in response to DNA strand breaks. Normal or non-proliferating cells are more apt to repair the DNA damage, but still some of the healthy cells will be damaged. Procarbazine is metabolized in the liver to an azo-derivative and then further metabolized by the cytochrome P-450 system to an active azoxy-derivative.

== References == {{Reflist}}

== External links == *[http://www.lymphomainfo.net/therapy/chemotherapy/mopp.html MOPP Treatment Regimen] *[http://virtualtrials.com/pcv.cfm PCV Information] *[http://www.merck.com/mmpe/lexicomp/procarbazine.html Procarbazine Drug Information Provided by Lexi-Comp – Merck Manual] *[https://web.archive.org/web/20060522193129/http://www.rxlist.com/cgi/generic3/procarb.htm RX Listing for Matulane] * {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/procarbazine | archive-url = https://web.archive.org/web/20160705220547/http://druginfo.nlm.nih.gov/drugportal/name/Procarbazine | archive-date = July 5, 2016 | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Procarbazine }}

Category:Benzamides Category:Cancer treatments Category:Disulfiram-like drugs Category:DNA replication inhibitors Category:Hydrazines Category:IARC Group 2A carcinogens Category:Isopropylamino compounds Category:Monoamine oxidase inhibitors Category:Mutagens Category:World Health Organization essential medicines Category:Wikipedia medicine articles ready to translate