Procarbazine

Last updated
Procarbazine
Procarbazine.svg
Procarbazine ball-and-stick.png
Clinical data
Trade names Matulane, Natulan, Indicarb, others
AHFS/Drugs.com Monograph
MedlinePlus a682094
Pregnancy
category
  • AU:D
Routes of
administration 		By mouth (gel capsule), intravenous
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Metabolism liver, kidney
Elimination half-life 10 minutes
Excretion kidney
Identifiers
  • N-Isopropyl-4-[(2-methylhydrazino)methyl]benzamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.010.531 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C12H19N3O
Molar mass 221.304 g·mol−1
3D model (JSmol)
  • O=C(c1ccc(cc1)CNNC)NC(C)C
  • InChI=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) Yes check.svgY
  • Key:CPTBDICYNRMXFX-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Procarbazine is a chemotherapy medication used for the treatment of Hodgkin's lymphoma and brain cancers. [1] For Hodgkin's 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. [1] It is typically taken by mouth. [1]

Contents

Common side effect include low blood cell counts and vomiting. [1] Other side effects include tiredness and depression. [2] [3] It is not recommended in people with severe liver or kidney problems. [4] Use in pregnancy is known to harm the baby. [1] Procarbazine is in the alkylating agents family of medication. [1] How it works is not clearly known. [1]

Procarbazine was approved for medical use in the United States in 1969. [1] It is on the World Health Organization's List of Essential Medicines. [5] [6] In the United Kingdom a month of treatment cost the National Health Service 450 to 750 pounds. [4]

Medical uses

When used to treat Hodgkin's 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's 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 should be 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. [2] 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. [2]

When combined with ethanol, procarbazine may cause a disulfiram-like reaction in some people. [2]

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. [2]

Procarbazine rarely causes chemotherapy-induced peripheral neuropathy, [7] 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. [8]

Pharmacology

Procarbazine works, in part, as an alkylating agent and methylates guanine at the O-6 position (much like dacarbazine also does [9] ). 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. [10] 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.

Synthesis

Patent: Procarbazine synthesis.svg
Patent:

Reaction of N-Isopropyl-4-Methylbenzamide [2144-17-4] (1) with diethyl azodicarboxylate [1972-28-7] (DEAD) (2) leads directly to the substituted hydrazine (3). Methylation by means of sodium hydride and methyl iodide proceeded at the less hindered amide (4). Acid hydrolysis of the carbethoxy groups leads to Procarbazine (5).

Related Research Articles

<span class="mw-page-title-main">Vincristine</span> Chemical compound; chemotherapy medication

Vincristine, also known as leurocristine and marketed under the brand name Oncovin among others, is a chemotherapy medication used to treat a number of types of cancer. This includes acute lymphocytic leukemia, acute myeloid leukemia, Hodgkin's disease, neuroblastoma, and small cell lung cancer among others. It is given intravenously.

<span class="mw-page-title-main">History of cancer chemotherapy</span>

The era of cancer chemotherapy began in the 1940s with the first use of nitrogen mustards and folic acid antagonist drugs. The targeted therapy revolution has arrived, but many of the principles and limitations of chemotherapy discovered by the early researchers still apply.

<span class="mw-page-title-main">Vinblastine</span> Chemical compound; chemotherapy medication

Vinblastine (VBL), sold under the brand name Velban among others, is a chemotherapy medication, typically used with other medications, to treat a number of types of cancer. This includes Hodgkin's lymphoma, non-small cell lung cancer, bladder cancer, brain cancer, melanoma, and testicular cancer. It is given by injection into a vein.

<span class="mw-page-title-main">Melphalan</span>

Melphalan, sold under the brand name Alkeran among others, is a chemotherapy medication used to treat multiple myeloma, ovarian cancer, melanoma, and AL amyloidosis. It is taken by mouth or by injection into a vein.

MOPP is a combination chemotherapy regimen used to treat Hodgkin lymphoma. The acronym is derived from the component drugs of the regimen:

<span class="mw-page-title-main">Dactinomycin</span> Chemical compound

Dactinomycin, also known as actinomycin D, is a chemotherapy medication used to treat a number of types of cancer. This includes Wilms tumor, rhabdomyosarcoma, Ewing's sarcoma, trophoblastic neoplasm, testicular cancer, and certain types of ovarian cancer. It is given by injection into a vein.

<span class="mw-page-title-main">Dacarbazine</span> A chemotherapy medication used for several cancer types

Dacarbazine (DTIC), also known as imidazole carboxamide, is a chemotherapy medication used in the treatment of melanoma and Hodgkin's lymphoma. For Hodgkin's it is often used together with vinblastine, bleomycin, and doxorubicin. It is given by injection into a vein.

CHOP is the acronym for a chemotherapy regimen used in the treatment of non-Hodgkin lymphoma. CHOP consists of:

<span class="mw-page-title-main">Chlorambucil</span>

Chlorambucil, sold under the brand name Leukeran among others, is a chemotherapy medication used to treat chronic lymphocytic leukemia (CLL), Hodgkin lymphoma, and non-Hodgkin lymphoma. For CLL it is a preferred treatment. It is given by mouth.

Stanford V, is a chemotherapy regimen intended as a first-line treatment for Hodgkin lymphoma. The regimen was developed in 1988, with the objective of maintaining a high remission rate while reducing the incidence of acute and long term toxicity, pulmonary damage, and sterility observed in alternative treatment regimens such as ABVD. The chemical agents used are:

<span class="mw-page-title-main">Ifosfamide</span> Chemotherapy medication

Ifosfamide (IFO), sold under the brand name Ifex among others, is a chemotherapy medication used to treat a number of types of cancer. This includes testicular cancer, soft tissue sarcoma, osteosarcoma, bladder cancer, small cell lung cancer, cervical cancer, and ovarian cancer. It is administered by injection into a vein.

<span class="mw-page-title-main">Lomustine</span>

Lomustine (INN); abbreviated as CCNU; original brand name CeeNU, now marketed as Gleostine) is an alkylating nitrosourea compound used in chemotherapy. It is closely related to semustine and is in the same family as streptozotocin. It is a highly lipid-soluble drug, thus it crosses the blood–brain barrier. This property makes it ideal for treating brain tumors, which is its primary use, although it is also used to treat Hodgkin lymphoma as a second-line option. Lomustine has a long time to nadir.

ABVD is a chemotherapy regimen used in the first-line treatment of Hodgkin lymphoma, replacing the older MOPP protocol. It consists of concurrent treatment with the chemotherapy drugs:

<span class="mw-page-title-main">Carmustine</span> Chemical compound

Carmustine, sold under the brand name BiCNU among others, is a medication used mainly for chemotherapy. It is a nitrogen mustard β-chloro-nitrosourea compound used as an alkylating agent.

<span class="mw-page-title-main">Pegaspargase</span>

Pegaspargase, sold under the brand name Oncaspar, is a medication used in the treatment of acute lymphoblastic leukemia (ALL). Often it is used together with anthracycline, vincristine, and corticosteroids. Pegaspargase can be administered either via an intravenous infusion or a intramuscular injection.

An alkylating antineoplastic agent is an alkylating agent used in cancer treatment that attaches an alkyl group (CnH2n+1) to DNA.

<span class="mw-page-title-main">Bendamustine</span>

Bendamustine, sold under the brand name Treanda among others, is a chemotherapy medication used in the treatment of chronic lymphocytic leukemia (CLL), multiple myeloma, and non-Hodgkin's lymphoma. It is given by injection into a vein.

Emil J. Freireich was an American hematologist, oncologist, and cancer biologist. He was recognized as a pioneer in the treatment of cancer and use of chemotherapy and is often known as the father of modern leukemia therapy.

VAMP regimen or VAMP chemotherapy is a four-drug combination chemotherapy regimen, used today in the treatment of Hodgkin lymphoma. It was one of the earliest combination chemotherapy regimens, originally developed as a treatment for childhood leukemia by a group of researchers at the National Cancer Institute led by Emil Frei and Emil Freireich. The first clinical trial of VAMP began in 1961. Because it was the first time that four chemotherapeutic agents were used at once, the trial was highly controversial at its time. Although new combination chemotherapy regimens have replaced the use of VAMP in the treatment of childhood leukemia, VAMP is considered an important precursor to modern treatments, confirming the effectiveness of combination chemotherapy and leading to the use of combination chemotherapy regimens to treat other types of cancer.

<span class="mw-page-title-main">Anaplastic oligodendroglioma</span> Human brain tumor

Anaplastic oligodendroglioma is a neuroepithelial tumor which is believed to originate from oligodendrocytes, a cell type of the glia. In the World Health Organization (WHO) classification of brain tumors, anaplastic oligodendrogliomas are classified as grade III. In the course of the disease, they can degenerate into WHO grade IV glioblastoma. The vast majority of oligodendrogliomas occur sporadically, without a confirmed cause and without inheritance within a family.

References

  1. 1 2 3 4 5 6 7 8 "Procarbazine Hydrochloride". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016.
  2. 1 2 3 4 5 "Procarbazine Capsules 50mg – Summary of Product Characteristics". UK Electronic Medicines Compendium. 24 November 2014. Archived from the original on 20 December 2016.
  3. ↑ World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR (eds.). WHO Model Formulary 2008. World Health Organization. p. 228. hdl: 10665/44053 . ISBN   9789241547659.
  4. 1 2 British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. p. 606. ISBN   9780857111562.
  5. ↑ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl: 10665/325771 . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  6. ↑ World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl: 10665/345533 . WHO/MHP/HPS/EML/2021.02.
  7. ↑ Lisa M. DeAngelis; Jerome B. Posner (2003). "Nonmetastatic Complications". In Kufe DW; Pollock RE; Weichselbaum RR; et al. (eds.). Holland-Frei Cancer Medicine (6th ed.). Hamilton (ON): BC Decker. Archived from the original on 2017-09-11.
  8. ↑ del Pino BM (Feb 23, 2010). "Chemotherapy-induced Peripheral Neuropathy". NCI Cancer Bulletin. 7 (4): 6. Archived from the original on 2011-12-11.
  9. ↑ Mauz-Körholz, Christine; Hasenclever, Dirk; Dörffel, Wolfgang; Ruschke, Kathrin; Pelz, Tanja; Voigt, Antje; Stiefel, Martina; Winkler, Melanie; Vilser, Constanze; Dieckmann, Karin; Karlén, Jonas; Bergsträsser, Eva; Fosså, Alexander; Mann, Georg; Hummel, Michael; Klapper, Wolfram; Stein, Harald; Vordermark, Dirk; Kluge, Regine; Körholz, Dieter (10 August 2010). "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 of Clinical Oncology. 28 (23): 3680–3686. doi:10.1200/JCO.2009.26.9381. PMID   20625128.
  10. ↑ Newton, Herbert (2006). Handbook of Brain Tumor Chemotherapy. Academic Press. ISBN   978-0-12-088410-0 . Retrieved 1 January 2021.
  11. ↑ BE618638 idem CH441366 idem W Bollag, H Gutmann, B Hegedus, A Kaiser, A Langemann, M Muller, P Zeller, U.S. Patent 3,795,678 (1962 to Hoffmann La Roche).
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.