Jump to content

Carboplatin: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous edit
Content deleted Content added
VisualWikitext
Canadamax (talk | contribs)
113 edits
→Research: ref name lang21
remove dosing
 
(43 intermediate revisions by 19 users not shown)
Line 1: Line 1:
{{Short description|Medication used to treat cancer}}
{{cs1 config|name-list-style=vanc}}
{{Infobox drug
{{Infobox drug
| Verifiedfields = changed
| Verifiedfields = changed
| verifiedrevid = 460018795
| verifiedrevid = 460018795
⚫
| IUPAC_name = ''cis''-diammine(cyclobutane-1,1-dicarboxylate-''O'',''O''')platinum(II)
| image = Carboplatin-skeletal.svg
| image = Carboplatin-skeletal.svg
| alt =
| image2 = Carboplatin-from-xtal-view-1-Mercury-3D-balls.png
| image2 = Carboplatin-from-xtal-view-1-Mercury-3D-balls.png
| alt2 =

<!--Clinical data-->
<!--Clinical data-->
⚫
| tradename = Paraplatin, others
| pronounce = {{IPAc-en|ˈ|k|ɑː|ɹ|b|oʊ|ˌ|p|l|æ|t|ə|n}}
| pronounce = {{IPAc-en|ˈ|k|ɑː|ɹ|b|oʊ|ˌ|p|l|æ|t|ə|n}}
⚫
| tradename = Paraplatin, others
⚫
| synonyms =
| Drugs.com = {{drugs.com|monograph|carboplatin}}
| Drugs.com = {{drugs.com|monograph|carboplatin}}
| MedlinePlus = a695017
| MedlinePlus = a695017
⚫
| routes_of_administration = [[Intravenous]]
| pregnancy_US = D
| legal_status = Rx Only
| ATC_prefix = L01
⚫
| ATC_suffix = XA02
⚫
| routes_of_administration = Intravenous
⚫
| ATC_supplemental =

| legal_CA = Rx-only
| legal_CA_comment = <ref>{{cite web | title=Product monograph brand safety updates | website=[[Health Canada]] | date=7 July 2016 | url=https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-product-database/label-safety-assessment-update/product-monograph-brand-safety-updates.html | access-date=3 April 2024}}</ref>
| legal_status = Rx-only

<!--Pharmacokinetic data-->
<!--Pharmacokinetic data-->
| bioavailability = complete
| bioavailability = complete
Line 19: Line 28:
| metabolism =
| metabolism =
| elimination_half-life = 1.1-2 hours
| elimination_half-life = 1.1-2 hours
| excretion = renal
| excretion = Kidney

<!--Identifiers-->
<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 41575-94-4
| CAS_number = 41575-94-4
| ATC_prefix = L01
⚫
| ATC_suffix = XA02
⚫
| ATC_supplemental =
| PubChem = 498142
| PubChem = 498142
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
Line 39: Line 46:
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 288376
| ChEMBL = 288376
⚫
| synonyms =

<!--Chemical data-->
<!--Chemical data-->
⚫
| IUPAC_name = ''cis''-diammine(cyclobutane-1,1-dicarboxylate-''O'',''O''')platinum(II)
| C=6 | H=12 | N=2 | O=4 | Pt=1
| C=6 | H=12 | N=2 | O=4 | Pt=1
| smiles = C1CC2(C1)C(=O)O[Pt-2]([NH3+])([NH3+])OC2=O
| smiles = C1CC2(C1)C(=O)O[Pt-2]([NH3+])([NH3+])OC2=O
Line 47: Line 57:
| StdInChIKey = OLESAACUTLOWQZ-UHFFFAOYSA-L
| StdInChIKey = OLESAACUTLOWQZ-UHFFFAOYSA-L
}}
}}

<!-- Definition and medical uses -->
<!-- Definition and medical uses -->
'''Carboplatin''', sold under the trade name '''Paraplatin''' among others, is a [[chemotherapy]] medication used to treat a number of forms of [[cancer]].<ref name=AHFS2016/> This includes [[ovarian cancer]], [[lung cancer]], [[head and neck cancer]], [[brain cancer]], and [[neuroblastoma]].<ref name=AHFS2016/> It is used by [[intravenous|injection into a vein]].<ref name=AHFS2016>{{cite web|title=Carboplatin|url=https://www.drugs.com/monograph/carboplatin.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161221012052/https://www.drugs.com/monograph/carboplatin.html|archive-date=21 December 2016}}</ref>
'''Carboplatin''', sold under the brand name '''Paraplatin''' among others, is a [[chemotherapy]] medication used to treat a number of forms of [[cancer]].<ref name=AHFS2016/> This includes [[ovarian cancer]], [[lung cancer]], [[head and neck cancer]], [[brain cancer]], and [[neuroblastoma]].<ref name=AHFS2016/> It is used by [[intravenous|injection into a vein]].<ref name=AHFS2016>{{cite web|title=Carboplatin|url=https://www.drugs.com/monograph/carboplatin.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161221012052/https://www.drugs.com/monograph/carboplatin.html|archive-date=21 December 2016}}</ref>


<!-- Side effect and mechanism -->
<!-- Side effect and mechanism -->
Side effects generally occur.<ref name=AHFS2016/> Common side effects include [[cytopenia|low blood cell levels]], nausea, and [[electrolyte problems]].<ref>{{cite journal |authors=Oun R, Moussa YE, Wheate NJ |year= 2018 |title= The side effects of platinum-based chemotherapy drugs: a review for chemists |journal= Dalton Transactions |volume= 47 |issue= 19 |pages= 6645–6653 |doi= 10.1039/c8dt00838h|pmid= 29632935 }}</ref><ref name=AHFS2016/> Other serious side effects include [[allergic reactions]] and increased future risk of another [[cancer]].<ref name=AHFS2016/> Use during [[pregnancy]] may result in harm to the baby.<ref name=AHFS2016/> Carboplatin is in the [[platinum-based antineoplastic]] family of medications and works by interfering with duplication of [[DNA]].<ref name=AHFS2016/><ref>{{cite journal |author= Apps, M. G. |author2= Choi, E. H. Y. |author3= Wheate, N. J. |year= 2015 |title= The state-of-play and future of platinum drugs |journal= Endocrine-Related Cancer |volume= 22 |issue= 4 |pages= 219–233 |pmid= 26113607 |doi= 10.1530/ERC-15-0237|doi-access= free }}</ref>
Side effects generally occur.<ref name=AHFS2016/> Common side effects include [[cytopenia|low blood cell levels]], nausea, and [[electrolyte problems]].<ref>{{cite journal | vauthors = Oun R, Moussa YE, Wheate NJ | title = The side effects of platinum-based chemotherapy drugs: a review for chemists | journal = Dalton Transactions | volume = 47 | issue = 19 | pages = 6645–6653 | date = May 2018 | pmid = 29632935 | doi = 10.1039/c8dt00838h }}</ref><ref name=AHFS2016/> Other serious side effects include [[allergic reactions]] and [[mutagenesis]]. It may be [[carcinogenic]], but further research is needed to confirm this.<ref name="AHFS2016" /> Use during [[pregnancy]] may result in harm to the baby.<ref name="AHFS2016" /> Carboplatin is in the [[platinum-based antineoplastic]] family of medications and works by interfering with duplication of [[DNA]].<ref name=AHFS2016/><ref>{{cite journal | vauthors = Apps MG, Choi EH, Wheate NJ | title = The state-of-play and future of platinum drugs | journal = Endocrine-Related Cancer | volume = 22 | issue = 4 | pages = R219–R233 | date = August 2015 | pmid = 26113607 | doi = 10.1530/ERC-15-0237 | doi-access = free | hdl = 2123/24426 | hdl-access = free }}</ref>


<!-- Society and culture -->
<!-- Society and culture -->
Carboplatin was patented in 1972 and approved for medical use in 1986.<ref name=Fis2006>{{cite book|last1=Fischer|first1=Janos|last2=Ganellin|first2=C. Robin|title=Analogue-based Drug Discovery|date=2006|publisher=John Wiley & Sons|isbn=9783527607495|page=513|url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA513|language=en|url-status=live|archive-url=https://web.archive.org/web/20161220163817/https://books.google.ca/books?id=FjKfqkaKkAAC&pg=PA513|archive-date=2016-12-20}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | 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>
Carboplatin was developed as a less toxic analogue of [[cisplatin]].<ref name="lebwohl"/> It was patented in 1972 and approved for medical use in 1989.<ref name=Fis2006>{{cite book| vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery|date=2006|publisher=John Wiley & Sons|isbn=9783527607495|page=513|url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA513|language=en|url-status=live|archive-url=https://web.archive.org/web/20161220163817/https://books.google.ca/books?id=FjKfqkaKkAAC&pg=PA513|archive-date=2016-12-20}}</ref> It is on the 2023 [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO23rd">{{cite book |title=The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) |vauthors=((World Health Organization)) |publisher=World Health Organization |year=2023 |location=Geneva |hdl=10665/371090 |id=WHO/MHP/HPS/EML/2023.02 |author-link=World Health Organization |hdl-access=free}}</ref>


==Medical uses==
==Medical uses==
Line 60: Line 71:


==Side effects==
==Side effects==
Relative to [[cisplatin]], the greatest benefit of carboplatin is its reduced side effects, particularly the elimination of [[nephrotoxicity|nephrotoxic]] effects. [[Nausea]] and [[vomiting]] are less severe and more easily controlled.
Relative to [[cisplatin]], the greatest benefit of carboplatin is its reduced side effects, particularly the elimination of [[nephrotoxicity|nephrotoxic]] effects. [[Nausea]] and [[vomiting]] are less severe and more easily controlled.<ref>{{Cite book |title=Manual of Hematopoietic Cell Transplantation and Cellular Therapies |vauthors=Gulbis AM, Wallis WD |year=2023 |pages=125–143 |chapter=10 - Preparative Regimens Used in Hematopoietic Cell Transplantation and Chimeric Antigen Receptor T-Cell Therapies |publisher=Elsevier |doi=10.1016/B978-0-323-79833-4.00010-3|isbn=9780323798334 }}</ref>


The main drawback of carboplatin is its myelosuppressive effect. This causes the [[blood cell]] and [[platelet]] output of bone marrow in the body to decrease quite dramatically, sometimes as low as 10% of its usual production levels. The nadir of this [[myelosuppression]] usually occurs 21–28 days after the first treatment, after which the blood cell and platelet levels in the blood begin to stabilize, often coming close to its pre-carboplatin levels. This decrease in [[white blood cell]]s ([[neutropenia]]) can cause complications, and is sometimes treated with drugs like [[filgrastim]]. The most notable complication of neutropenia is increased probability of infection by opportunistic organisms, which necessitates [[hospital readmission]] and treatment with [[antibiotic]]s.
The main drawback of carboplatin is its myelosuppressive effect. This causes the [[blood cell]] and [[platelet]] output of bone marrow in the body to decrease quite dramatically, sometimes as low as 10% of its usual production levels. The nadir of this [[myelosuppression]] usually occurs 21–28 days after the first treatment, after which the blood cell and platelet levels in the blood begin to stabilize, often coming close to its pre-carboplatin levels. This decrease in [[white blood cell]]s ([[neutropenia]]) can cause complications, and is sometimes treated with drugs like [[filgrastim]]. The most notable complication of neutropenia is increased probability of infection by opportunistic organisms, which necessitates [[hospital readmission]] and treatment with [[antibiotic]]s.

==Chemistry==
⚫
In terms of its structure, carboplatin differs from cisplatin in that it has a [[bidentate]] dicarboxylate (the ligand is CycloButane DiCarboxylic Acid, CBDCA) in place of the two [[chloride]] [[ligand]]s, which are the [[leaving group]]s in cisplatin. For this reason, "CBDCA" is sometimes used in the medical literature as an abbreviation referring to carboplatin. Carboplatin exhibits lower reactivity and slower DNA binding kinetics, although it forms the same reaction products ''in vitro'' at equivalent doses with cisplatin. Unlike cisplatin, carboplatin may be susceptible to alternative mechanisms. Some results show that cisplatin and carboplatin cause different morphological changes in [[MCF-7]] cell lines while exerting their cytotoxic behaviour.<ref>{{cite journal |vauthors=Natarajan G, Malathi R, Holler E|title=Increased DNA-binding activity of cis-1,1-cyclobutanedicarboxylatodiammineplatinum(II) (carboplatin) in the presence of nucleophiles and human breast cancer MCF-7 cell cytoplasmic extracts: activation theory revisited |journal=[[Biochemical Pharmacology (journal)|Biochemical Pharmacology]] |volume=58 |issue=10 |pages=1625–29 |date=November 1999 |pmid=10535754 |doi=10.1016/S0006-2952(99)00250-6}}</ref> The diminished reactivity limits protein-carboplatin complexes, which are excreted. The lower excretion rate of carboplatin means that more is retained in the body, and hence its effects are longer lasting (a retention half-life of 30 hours for carboplatin, compared to 1.5-3.6 hours in the case of cisplatin).


==Mechanism of action==
==Mechanism of action==
⚫
Carboplatin differs from cisplatin in that it has a [[bidentate]] dicarboxylate (the ligand is cyclobutane dicarboxylate, CBDCA) in place of the two [[chloride]] [[ligand]]s. Both drugs are [[alkylating agent]]s. CBDCA and chloride are the [[leaving group]]s in these respective drugs Carboplatin exhibits slower [[aquation]] (replacement of CBDCA by water) and thus slower DNA binding kinetics, although it forms the same reaction products ''in vitro'' at equivalent doses with cisplatin. Unlike cisplatin, carboplatin may be susceptible to alternative mechanisms. Some results show that cisplatin and carboplatin cause different morphological changes in [[MCF-7]] cell lines while exerting their cytotoxic behaviour.<ref>{{cite journal | vauthors = Natarajan G, Malathi R, Holler E | title = Increased DNA-binding activity of cis-1,1-cyclobutanedicarboxylatodiammineplatinum(II) (carboplatin) in the presence of nucleophiles and human breast cancer MCF-7 cell cytoplasmic extracts: activation theory revisited | journal = Biochemical Pharmacology | volume = 58 | issue = 10 | pages = 1625–1629 | date = November 1999 | pmid = 10535754 | doi = 10.1016/S0006-2952(99)00250-6 }}</ref> The diminished reactivity limits protein-carboplatin complexes, which are excreted. The lower excretion rate of carboplatin means that more is retained in the body, and hence its effects are longer lasting (a retention half-life of 30 hours for carboplatin, compared to 1.5-3.6 hours in the case of cisplatin).
Two theories exist to explain the molecular [[mechanism of action]] of carboplatin with DNA:
*[[Aquation]], or the like-cisplatin hypothesis.
*[[Activation]], or the unlike-cisplatin hypothesis.
The former is more accepted owing to the similarity of the leaving groups with its predecessor cisplatin, while the latter hypothesis envisages a biological activation mechanism to release the active Pt<sup>2+</sup> species.


Like cisplatin, carboplatin binds to and cross-links DNA, interfering with the replication and suppressing growth of the cancer cell.<ref>{{cite journal | vauthors = Noll DM, Mason TM, Miller PS | title = Formation and repair of interstrand cross-links in DNA | journal = Chemical Reviews | volume = 106 | issue = 2 | pages = 277–301 | date = February 2006 | pmid = 16464006 | pmc = 2505341 | doi = 10.1021/cr040478b }}</ref><ref>{{Cite book |title=Encyclopedia of Respiratory Medicine |vauthors=Edelman MJ, Rupard EJ |year=2006 |pages=332–338 |chapter=TUMORS, MALIGNANT / Chemotherapeutic Agents |publisher=Academic Press |doi=10.1016/B0-12-370879-6/00409-9|isbn=9780123708793 }}</ref>
==Dose==
Calvert's formula is used to calculate the dose of carboplatin. It takes under consideration the creatinine clearance and the desired [[Area under the curve (pharmacokinetics)|area under curve]].<ref name=MSKCC_Dosing>{{cite web |url=http://www.mskcc.org/cancer-care/clinical-update/new-guidelines-carboplatin-dosing |title=New Guidelines for Carboplatin Dosing|first1=Roisin|last1=O'Cearbhaill, MD |first2=Paul S.|last2=Sabbatini, MD|date=September 1, 2012|publisher=Memorial Sloan Kettering Cancer Center|access-date=2014-03-27 |url-status=live |archive-url=https://web.archive.org/web/20141031014904/http://www.mskcc.org/cancer-care/clinical-update/new-guidelines-carboplatin-dosing |archive-date=2014-10-31 }}</ref> After 24 hours, close to 70% of carboplatin is excreted in the urine unchanged. This means that the dose of carboplatin must be adjusted for any impairment in [[kidney function]].<ref name=":0">{{Cite journal|last1=Calvert|first1=A H|last2=Newell|first2=D R|last3=Gumbrell|first3=L A|last4=O'Reilly|first4=S|last5=Burnell|first5=M|last6=Boxall|first6=F E|last7=Siddik|first7=Z H|last8=Judson|first8=I R|last9=Gore|first9=M E|date=1989-11-01|title=Carboplatin dosage: prospective evaluation of a simple formula based on renal function.|journal=Journal of Clinical Oncology|volume=7|issue=11|pages=1748–1756|doi=10.1200/JCO.1989.7.11.1748|pmid=2681557|issn=0732-183X}}</ref>


== Synthesis ==
Calvert formula: <math>Dose(mg)= AUC \cdot (GFR + 25)</math>
Cisplatin reacts with [[silver nitrate]] and then cyclobutane-1,1-dicarboxylic acid to form carboplatin.<ref>{{Cite book |title=Synthesis of Essential Drugs |vauthors=Vardanyan RS, Hruby VJ |year=2006 |pages=389–418 |chapter=30 - Antineoplastics |publisher=Elsevier |doi=10.1016/B978-044452166-8/50030-3|isbn=9780444521668 }}</ref>

[[File:Carboplatin synthesis.png|center|thumb|500x131px]]
The typical area under the curve (AUC) for carboplatin ranges from 3-7 (mg/ml)*min.<ref name=":0" />


==History==
==History==
Carboplatin was discovered at [[Michigan State University]],<ref>{{cite web|url= http://news.msu.edu/story/1218/|title= Discovery to Market: Fact Sheet|url-status= live|archive-url= https://web.archive.org/web/20120208160116/http://news.msu.edu/story/1218/|archive-date= 2012-02-08}}</ref> and developed at the [[Institute of Cancer Research]] in London. [[Bristol-Myers Squibb]] gained [[Food and Drug Administration]] (FDA) approval for carboplatin, under the brand name Paraplatin, in March 1989. Starting in October 2004, generic versions of the drug became available.
Carboplatin, a cisplatin analogue, was developed by [[Bristol Myers Squibb]] and the [[Institute of Cancer Research]] in order to reduce the toxicity of cisplatin.<ref name="lebwohl">{{Cite journal |vauthors=Lebwohl D, Canetta R |year=1998 |title=Clinical development of platinum complexes in cancer therapy: an historical perspective and an update |url=https://www.ejcancer.com/action/showPdf?pii=S0959-8049%2898%2900224-X |journal=Eur J Cancer |volume=34 |issue=10 |pages=1522–34 |doi=10.1016/s0959-8049(98)00224-x |pmid=9893623}}</ref><ref>{{Cite web |title=Discovering early chemotherapy drugs |url=https://www.icr.ac.uk/about-us/our-achievements/our-scientific-discoveries/we-discovered-chemotherapeutic-agents-which-are-still-in-use-more-than-50-years-later |access-date=2023-10-06 |website=Institute of Cancer Research}}</ref> It gained U.S. [[Food and Drug Administration]] (FDA) approval for carboplatin, under the brand name Paraplatin, in March 1989. Starting in October 2004, generic versions of the drug became available.


==Research==
==Research==
Carboplatin has also been used for [[adjuvant therapy]] of stage 1 [[seminoma|seminomatous testicular cancer]]. Research has indicated that it is not less effective than adjuvant radiotherapy for this treatment, while having fewer side effects.<ref>{{cite journal |vauthors=Oliver RT, Mason MD, Mead GM, von der Maase H, Rustin GJ, Joffe JK, de Wit R, Aass N, Graham JD, Coleman R, Kirk SJ, Stenning SP |title=Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial |journal=Lancet |volume=366 |issue=9482 |pages=293–300 |year=2005 |pmid=16039331 |doi=10.1016/S0140-6736(05)66984-X|s2cid=6001898 }}</ref> This has led to carboplatin based adjuvant therapy being generally preferred over adjuvant radiotherapy in clinical practice.<ref>{{cite journal |vauthors=Toner GC |title=Testicular cancer: Optimal management of stage I seminoma in 2015 |journal=Nat Rev Urol |volume=12 |issue=5 |pages=249–51 |year=2015 |pmid=25896179 |doi=10.1038/nrurol.2015.85 |s2cid=8072355 }}</ref>
Carboplatin has also been used for [[adjuvant therapy]] of stage 1 [[seminoma|seminomatous testicular cancer]]. Research has indicated that it is not less effective than adjuvant [[radiotherapy]] for this treatment, while having fewer side effects.<ref>{{cite journal | vauthors = Oliver RT, Mason MD, Mead GM, von der Maase H, Rustin GJ, Joffe JK, de Wit R, Aass N, Graham JD, Coleman R, Kirk SJ, Stenning SP | display-authors = 6 | title = Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial | journal = Lancet | volume = 366 | issue = 9482 | pages = 293–300 | year = 2005 | pmid = 16039331 | doi = 10.1016/S0140-6736(05)66984-X | s2cid = 6001898 | doi-access = free }}</ref> This has led to carboplatin based adjuvant therapy being generally preferred over adjuvant radiotherapy in clinical practice.<ref>{{cite journal | vauthors = Toner GC | title = Testicular cancer: Optimal management of stage I seminoma in 2015 | journal = Nature Reviews. Urology | volume = 12 | issue = 5 | pages = 249–251 | date = May 2015 | pmid = 25896179 | doi = 10.1038/nrurol.2015.85 | s2cid = 8072355 }}</ref>


Carboplatin combined with [[hexadecyl]] chain and [[polyethylene glycol]] appears to have increased [[liposolubility]] and [[PEGylation]]. This is useful in [[chemotherapy]], specifically non-small cell [[lung cancer]].<ref name="lang21">{{cite journal |doi=10.1080/10717544.2021.1938754}}</ref>
Carboplatin combined with [[hexadecyl]] chain and [[polyethylene glycol]] appears to have increased [[liposolubility]] and [[PEGylation]]. This is useful in [[chemotherapy]], specifically for non-small cell [[lung cancer]].<ref name="lang21">{{cite journal | vauthors = Lang T, Li N, Zhang J, Li Y, Rong R, Fu Y | title = Prodrug-based nano-delivery strategy to improve the antitumor ability of carboplatin ''in vivo'' and ''in vitro'' | journal = Drug Delivery | volume = 28 | issue = 1 | pages = 1272–1280 | date = December 2021 | pmid = 34176381 | pmc = 8238065 | doi = 10.1080/10717544.2021.1938754 }}</ref>


==See also==
== References ==
*[[Cisplatin]]
*[[Dicycloplatin]]

==References==
{{Reflist}}
{{Reflist}}


== Further reading ==
==Additional references==
* {{cite journal | vauthors = Canetta R, Rozencweig M, Carter SK | title = Carboplatin: the clinical spectrum to date | journal = Cancer Treatment Reviews | volume = 12 Suppl A | issue = Suppl A | pages = 125–136 | date = September 1985 | pmid = 3002623 | doi = 10.1016/0305-7372(85)90027-1 }}
{{Refbegin}}
*{{cite journal |vauthors=Canetta R, Rozencweig M, Carter SK |title=Carboplatin: the clinical spectrum to date |journal=Cancer Treat. Rev. |volume=12 |issue=Suppl A |pages=125–36 |date=September 1985 |pmid=3002623 |doi=10.1016/0305-7372(85)90027-1}}
* {{cite journal | vauthors = Yang XL, Wang AH | title = Structural studies of atom-specific anticancer drugs acting on DNA | journal = Pharmacology & Therapeutics | volume = 83 | issue = 3 | pages = 181–215 | date = September 1999 | pmid = 10576292 | doi = 10.1016/S0163-7258(99)00020-0 }}
*{{cite journal |vauthors=Yang XL, Wang AH |title=Structural studies of atom-specific anticancer drugs acting on DNA |journal=Pharmacol. Ther. |volume=83 |issue=3 |pages=181–215 |date=September 1999 |pmid=10576292 |doi=10.1016/S0163-7258(99)00020-0}}
{{Refend}}

==External links==
<!-- MedlinePlus link is available under Clinical Data -->
*[http://kccrc.org/calculator/#calc-holder-2 Creatinine Clearence &#91;sic&#93; Calculator]
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/carboplatin | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Carboplatin }}


{{Chemotherapeutic agents}}
{{Chemotherapeutic agents}}
{{Platinum compounds}}
{{Platinum compounds}}

{{Portal bar|Medicine}}
{{Portal bar|Medicine}}


[[Category:Ammine complexes]]
[[Category:Ammine complexes]]
[[Category:Coordination compounds]]
[[Category:Coordination complexes]]
[[Category:Cyclobutanes]]
[[Category:Cyclobutanes]]
[[Category:Organoplatinum compounds]]
[[Category:Organoplatinum compounds]]

Latest revision as of 09:06, 27 December 2024

Carboplatin
Clinical data
Pronunciation/ˈkɑːrboʊˌplætən/
Trade namesParaplatin, others
AHFS/Drugs.comMonograph
MedlinePlusa695017
Routes of
administration		Intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailabilitycomplete
Protein bindingVery low
Elimination half-life1.1-2 hours
ExcretionKidney
Identifiers
  • cis-diammine(cyclobutane-1,1-dicarboxylate-O,O')platinum(II)
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.050.388 Edit this at Wikidata
Chemical and physical data
FormulaC6H12N2O4Pt
Molar mass371.256 g·mol−1
3D model (JSmol)
  • C1CC2(C1)C(=O)O[Pt-2]([NH3+])([NH3+])OC2=O
  • InChI=1S/C6H8O4.2H3N.Pt/c7-4(8)6(5(9)10)2-1-3-6;;;/h1-3H2,(H,7,8)(H,9,10);2*1H3;/q;;;+2/p-2 checkY
  • Key:OLESAACUTLOWQZ-UHFFFAOYSA-L checkY
 ☒NcheckY (what is this?)  (verify)

Carboplatin, sold under the brand name Paraplatin among others, is a chemotherapy medication used to treat a number of forms of cancer.[3] This includes ovarian cancer, lung cancer, head and neck cancer, brain cancer, and neuroblastoma.[3] It is used by injection into a vein.[3]

Side effects generally occur.[3] Common side effects include low blood cell levels, nausea, and electrolyte problems.[4][3] Other serious side effects include allergic reactions and mutagenesis. It may be carcinogenic, but further research is needed to confirm this.[3] Use during pregnancy may result in harm to the baby.[3] Carboplatin is in the platinum-based antineoplastic family of medications and works by interfering with duplication of DNA.[3][5]

Carboplatin was developed as a less toxic analogue of cisplatin.[6] It was patented in 1972 and approved for medical use in 1989.[7] It is on the 2023 World Health Organization's List of Essential Medicines.[8]

Medical uses

[edit]

Carboplatin is used to treat a number of forms of cancer. This includes ovarian cancer, lung cancer, head and neck cancer, brain cancer, and neuroblastoma. It may be used for some types of testicular cancer but cisplatin is generally more effective.[3] It has also been used to treat triple-negative breast cancer.

Side effects

[edit]

Relative to cisplatin, the greatest benefit of carboplatin is its reduced side effects, particularly the elimination of nephrotoxic effects. Nausea and vomiting are less severe and more easily controlled.[9]

The main drawback of carboplatin is its myelosuppressive effect. This causes the blood cell and platelet output of bone marrow in the body to decrease quite dramatically, sometimes as low as 10% of its usual production levels. The nadir of this myelosuppression usually occurs 21–28 days after the first treatment, after which the blood cell and platelet levels in the blood begin to stabilize, often coming close to its pre-carboplatin levels. This decrease in white blood cells (neutropenia) can cause complications, and is sometimes treated with drugs like filgrastim. The most notable complication of neutropenia is increased probability of infection by opportunistic organisms, which necessitates hospital readmission and treatment with antibiotics.

Mechanism of action

[edit]

Carboplatin differs from cisplatin in that it has a bidentate dicarboxylate (the ligand is cyclobutane dicarboxylate, CBDCA) in place of the two chloride ligands. Both drugs are alkylating agents. CBDCA and chloride are the leaving groups in these respective drugs Carboplatin exhibits slower aquation (replacement of CBDCA by water) and thus slower DNA binding kinetics, although it forms the same reaction products in vitro at equivalent doses with cisplatin. Unlike cisplatin, carboplatin may be susceptible to alternative mechanisms. Some results show that cisplatin and carboplatin cause different morphological changes in MCF-7 cell lines while exerting their cytotoxic behaviour.[10] The diminished reactivity limits protein-carboplatin complexes, which are excreted. The lower excretion rate of carboplatin means that more is retained in the body, and hence its effects are longer lasting (a retention half-life of 30 hours for carboplatin, compared to 1.5-3.6 hours in the case of cisplatin).

Like cisplatin, carboplatin binds to and cross-links DNA, interfering with the replication and suppressing growth of the cancer cell.[11][12]

Synthesis

[edit]

Cisplatin reacts with silver nitrate and then cyclobutane-1,1-dicarboxylic acid to form carboplatin.[13]

History

[edit]

Carboplatin, a cisplatin analogue, was developed by Bristol Myers Squibb and the Institute of Cancer Research in order to reduce the toxicity of cisplatin.[6][14] It gained U.S. Food and Drug Administration (FDA) approval for carboplatin, under the brand name Paraplatin, in March 1989. Starting in October 2004, generic versions of the drug became available.

Research

[edit]

Carboplatin has also been used for adjuvant therapy of stage 1 seminomatous testicular cancer. Research has indicated that it is not less effective than adjuvant radiotherapy for this treatment, while having fewer side effects.[15] This has led to carboplatin based adjuvant therapy being generally preferred over adjuvant radiotherapy in clinical practice.[16]

Carboplatin combined with hexadecyl chain and polyethylene glycol appears to have increased liposolubility and PEGylation. This is useful in chemotherapy, specifically for non-small cell lung cancer.[17]

References

[edit]
  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  2. ^ "Product monograph brand safety updates". Health Canada. 7 July 2016. Retrieved 3 April 2024.
  3. ^ a b c d e f g h i "Carboplatin". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016.
  4. ^ Oun R, Moussa YE, Wheate NJ (May 2018). "The side effects of platinum-based chemotherapy drugs: a review for chemists". Dalton Transactions. 47 (19): 6645–6653. doi:10.1039/c8dt00838h. PMID 29632935.
  5. ^ Apps MG, Choi EH, Wheate NJ (August 2015). "The state-of-play and future of platinum drugs". Endocrine-Related Cancer. 22 (4): R219 – R233. doi:10.1530/ERC-15-0237. hdl:2123/24426. PMID 26113607.
  6. ^ a b Lebwohl D, Canetta R (1998). "Clinical development of platinum complexes in cancer therapy: an historical perspective and an update". Eur J Cancer. 34 (10): 1522–34. doi:10.1016/s0959-8049(98)00224-x. PMID 9893623.
  7. ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 513. ISBN 9783527607495. Archived from the original on 2016-12-20.
  8. ^ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
  9. ^ Gulbis AM, Wallis WD (2023). "10 - Preparative Regimens Used in Hematopoietic Cell Transplantation and Chimeric Antigen Receptor T-Cell Therapies". Manual of Hematopoietic Cell Transplantation and Cellular Therapies. Elsevier. pp. 125–143. doi:10.1016/B978-0-323-79833-4.00010-3. ISBN 9780323798334.
  10. ^ Natarajan G, Malathi R, Holler E (November 1999). "Increased DNA-binding activity of cis-1,1-cyclobutanedicarboxylatodiammineplatinum(II) (carboplatin) in the presence of nucleophiles and human breast cancer MCF-7 cell cytoplasmic extracts: activation theory revisited". Biochemical Pharmacology. 58 (10): 1625–1629. doi:10.1016/S0006-2952(99)00250-6. PMID 10535754.
  11. ^ Noll DM, Mason TM, Miller PS (February 2006). "Formation and repair of interstrand cross-links in DNA". Chemical Reviews. 106 (2): 277–301. doi:10.1021/cr040478b. PMC 2505341. PMID 16464006.
  12. ^ Edelman MJ, Rupard EJ (2006). "TUMORS, MALIGNANT / Chemotherapeutic Agents". Encyclopedia of Respiratory Medicine. Academic Press. pp. 332–338. doi:10.1016/B0-12-370879-6/00409-9. ISBN 9780123708793.
  13. ^ Vardanyan RS, Hruby VJ (2006). "30 - Antineoplastics". Synthesis of Essential Drugs. Elsevier. pp. 389–418. doi:10.1016/B978-044452166-8/50030-3. ISBN 9780444521668.
  14. ^ "Discovering early chemotherapy drugs". Institute of Cancer Research. Retrieved 2023-10-06.
  15. ^ Oliver RT, Mason MD, Mead GM, von der Maase H, Rustin GJ, Joffe JK, et al. (2005). "Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial". Lancet. 366 (9482): 293–300. doi:10.1016/S0140-6736(05)66984-X. PMID 16039331. S2CID 6001898.
  16. ^ Toner GC (May 2015). "Testicular cancer: Optimal management of stage I seminoma in 2015". Nature Reviews. Urology. 12 (5): 249–251. doi:10.1038/nrurol.2015.85. PMID 25896179. S2CID 8072355.
  17. ^ Lang T, Li N, Zhang J, Li Y, Rong R, Fu Y (December 2021). "Prodrug-based nano-delivery strategy to improve the antitumor ability of carboplatin in vivo and in vitro". Drug Delivery. 28 (1): 1272–1280. doi:10.1080/10717544.2021.1938754. PMC 8238065. PMID 34176381.

Further reading

[edit]
Retrieved from "https://en.wikipedia.org/enwiki/w/index.php?title=Carboplatin&oldid=1265518815"