A platinum-containing chemotherapeutic drug, Cl2H6N2Pt, used in the treatment of metastatic ovarian or testicular cancers and advanced bladder cancer.
[CIS– + PLATIN(UM).]
|
Results for cisplatin
|
On this page:
|
Oncology Encyclopedia:
Cisplatin
Key Terms: Anemia, Chemotherapy, DNA, Electrolytes, Food and Drug Administration, Intravenous, Metastatic, Neutropenia.
Definition
Cisplatin, also known by the brand name Platinol-AQ, Cis-platinum, CDDP, or DDP, is a chemotherapy medicine used to treat certain types of cancer by destroying cancerous cells.
Purpose
Cisplatin is approved by the Food and Drug Administration (FDA) to treat metastatic testicular cancer and metastatic ovarian cancer. It is also approved for late-stage bladder cancer and has been used to treat other types of cancer including head and neck cancer, esophageal cancer, stomach cancer, lung cancer, skin cancer, prostate cancer, lymphoma and others (breast, neuroblastoma, sarcoma, bladder, cervical, myeloma, mesothelioma, osteosarcoma).
Description
Cisplatin is a member of the group of chemotherapy drugs known as heavy metal alkylating-like agents. These drugs interfere with the genetic material (DNA) inside the cancer cells and prevent them from further dividing and growing more cancer cells.
Cisplatin has been used to treat cancer for more than 30 years. It can be used alone or in combination with other chemotherapies, including bleomycin-etoposide, ifosfamide, gemcitabine, paclitaxel, fluorouracil-leucovorin, vinorelbine, methotrexate-vinblastine-doxorubicin. Cisplatin may also be given with radiation therapy.
Recommended dosage A cisplatin dose can be determined using a mathematical calculation that measures body surface area (BSA), which depends on a person's overall size. Body surface area is measured in the units known as square meter (m2). The body surface area is calculated and then multiplied by the drug dosage in milligrams per m2 (mg/m2), which gives the proper dosage.
Cisplatin is a clear, colorless solution administered by an infusion into a vein. Infusions can be given once every three to four weeks over a 30 minutes up to two hours. It can also be given continuously over 24 hours a day for several days in a row. One cycle of cisplatin should not be given more frequently than once every three to four weeks. Dosages depend on the cancer being treated.
To Treat Metastatic Testicular Cancer
Dosages are 20 mg/m2 per day administered into a vein every day for five days in a row. This regimen is used in combination with other chemotherapy drugs, mainly bleomycin and etoposide or vinblastine.
To Treat Metastatic Ovarian Cancer
Dosages are 50 mg/m2 to 100 mg/m2 administered into a vein once every four weeks. This regimen can be combined with the chemotherapy drug cyclophosphamide or doxorubicin.
To Treat Advanced Bladder Cancer
Cisplatin doses range from 50 mg/m2 to 70 mg/m2 administered into a vein once every 3 to 4 weeks. Cisplatin is usually given alone for bladder cancer.
Before receiving cisplatin large volumes of intravenous fluids are given to keep the kidneys flushed with water. If patients have severe kidney problems the physician will either not use cisplatin or decrease the dose being used.
Normal metal ions found in the body, called electrolytes, can be lost due to administration of cisplatin. These may be added to these intravenous fluids for replacement.
Precautions
When receiving cisplatin, it is important to drink a lot of fluids to help flush the kidneys and prevent kidney damage. Patients also receive additional fluids through their veins before, during, and after receiving cisplatin.
Blood counts will be monitored regularly while on cisplatin therapy. During a certain time period after receiving cisplatin, there is an increased risk of getting infections. Caution should be taken to avoid unnecessary exposure to crowds and people with infections.
Patients with a known previous allergic reaction to chemotherapy drugs or any other medications should tell their doctor.
Patients who may be pregnant or trying to become pregnant should also tell their doctor before receiving cisplatin.
Chemotherapy can cause men and women to be sterile (not able to have children).
Patients should check with their doctors before receiving live virus vaccines while on chemotherapy.
An additional difficulty that can arise with cisplatin and other platinum-based anticancer drugs is that some tumor cells develop resistance to the drug. These resistant cells can then regrow and multiply. One strategy against drug resistance is to develop new drugs that can be used together with cisplatin to target resistant cells. In February 2004 the FDA approved pemetrexed (Alimta) for use together with cisplatin in the treatment of certain types of lung cancer. Another strategy for defeating tumor resistance to cisplatin is genetic modification of the resistant tumor cells. This approach in still in the early stages of experimentation as of 2004.
Side Effects
Common side effects include nausea and vomiting, which can begin from 1 hour after receiving the drug and last as long as a week. Patients are given medicines known as antiemetics, before and after receiving cisplatin to help prevent or decrease this side effect. Diarrhea has also been known to occur.
A serious common side effect related to the total dose of cisplatin received is kidney damage, which can occur in up to one-third of patients. Taking fluids before, during and after receiving cisplatin help prevent this from occurring. In addition, some researchers in Brazil have reported that quercetin, a yellowish plant pigment found in apples and onions, shows promise as a protective treatment against kidney damage related to cisplatin.
Hearing damage can also occur in up to one-third of patients. Patients may experience ringing in the ears and hearing loss of high-pitched frequency. Hearing tests may be requested before and/or after cisplatin therapy. One promising treatment for cisplatin-related hearing damage is vitamin E, which is being studied by a group of researchers in Illinois.
Low blood counts, referred to as myelosuppression, are expected due to cisplatin administration. When the white blood cell count is low this is called neutropenia and patients are at an increased risk of developing a fever and infections. Platelets are blood cells in the body that allow for the formation of clots. When the platelet count is low, patients are at an increased risk for bruising and bleeding. Low red blood cell counts, referred to as anemia, may also occur due to cisplatin administration. Low red counts make people feel tired.
Cisplatin can also cause damage to nerves and nervous system tissues. Patients may feel tingling, numbness and sometimes burning of the fingers and toes. This side effect is common and can be severe.
Less common side effects include change of taste sensation, loss of appetite, dizziness, seizures, confusion, muscle cramps, and uncontrolled muscle contractions. Men treated with cisplatin for testicular cancer sometimes develop so-called dry ejaculations. Other side effects include, hair loss (alopecia), hiccups, rash, allergic reactions with difficulty breathing, swelling, and a fast heart rate.
Cisplatin may cause the body to waste normal electrolytes that circulate in the body (potassium, magnesium, phosphate, sodium, calcium) resulting in low levels of these electrolytes. These will be monitored by the doctor and replacement drugs will be given if necessary.
All side effects should be reported to the doctor or nurse.
Interactions
Patients should avoid other drugs that may cause damage to the kidneys.
Certain water pills and cisplatin given together may increase the risk of hearing damage. Before starting any medications, patients should notify their doctors.
Cisplatin may make medications that control seizures less effective.
Resources
Books
Karch, A. M. Lippincott's Nursing Drug Guide. Springhouse, PA: Lippincott Williams & Wilkins, 2003.
Periodicals
Fossa, S. D. "Long-Term Sequelae after Cancer Therapy—Survivorship After Treatment for Testicular Cancer." Acta Oncologica 43 (February 2004): 134–141.
Francescato, H. D., T. M. Coimbra, R. S. Costa, and L. Bianchi Mde. "Protective Effect of Quercetin on the Evolution of Cisplatin-Induced Acute Tubular Necrosis." Kidney and Blood Pressure Research 27 (March 2004): 148–158.
Funato, T. "Utility of Antioncogene Ribozymes and Antisense Oligonucleotides in Reversing Drug Resistance." Methods in Molecular Medicine 106 (2004): 215–234.
Hazarika, M., R. M. White, J. R. Johnson, and R. Pazdur. "FDA Drug Approval Summaries: Pemetrexed (Alimta)." Oncologist 9 (March 2004): 482–488.
Kalkanis, J. G., C. Whitworth, and L. P. Rybak. "Vitamin E Reduces Cisplatin Ototoxicity." Laryngoscope 114 (March 2004): 538–542.
Organizations
American Society of Health-System Pharmacists (ASHP). 7272 Wisconsin Avenue, Bethesda, MD 20814. (301) 657-3000.
United States Food and Drug Administration (FDA). 5600 Fishers Lane, Rockville, MD 20857-0001. (888) INFO-FDA.
—Nancy J. Beaulieu, RPh., BCOP; Rebecca J. Frey, PhD
Dental Dictionary:
cisplatin
n
An antineoplastic prescribed in the treatment of a wide variety of neoplasms such as metastatic testicular, prostatic, and ovarian tumors.
Drug Info:
Cisplatin
Brand names: Platinol®, Platinol®-AQ
Chemical formula:
- Español:
- Inyección de cisplatino
Cisplatin injection
What is cisplatin injection?
CISPLATIN (Platinol®) is a chemotherapy agent used for treating many types of cancer including bladder, head and neck, lung, ovarian, sarcoma, and testicular cancers. Cisplatin interferes with the growth of rapidly dividing cells, like cancer cells, and eventually causes these cells to die. Cisplatin may be used alone or with other chemotherapy agents or radiation therapy. Generic cisplatin injections are not yet available.
What should I tell my health care provider before I take this medicine?
They need to know if you have any of these conditions:
• an active infection
• blood disorders
• dental disease
• gout
• hearing problems
• kidney disease
• loss of feeling, pain or numbness in the hands or feet
• recent radiation therapy
• an unusual or allergic reaction to cisplatin, carboplatin, other chemotherapy, other medicines, foods, dyes, or preservatives
• pregnant or trying to get pregnant
• breast-feeding
How should I use this medicine?
Cisplatin is for injection or infusion into a vein. It is usually administered in a hospital or clinic setting by a specially trained health care professional. You will be given an infusion once every 3—4 weeks depending upon your laboratory results.
Cisplatin may also be given directly into your abdomen. During this procedure, cisplatin is infused into your abdomen and then drained out after 2—4 hours. During this time you may need to change positions frequently to ensure the cisplatin reaches the tumor. This treatment is given every 3—4 weeks.
Contact your pediatrician or health care professional regarding the use of this medicine in children. Special care may be needed.
What drug(s) may interact with cisplatin?
• certain antibiotics (such as amphoteracin B. amikacin, gentamicin, neomycin, streptomycin, tobramycin)
• digoxin
• diuretic or water pills (such as furosemide, torsemide, ethacrynic acid, bumetanide)
• dofetilide
• dipyridamole
• medicines to treat blood clots, such as 'blood thinners' (example: warfarin or Coumadin®)
• mesna
• methotrexate
• other chemotherapy agents may increase the side effects seen with cisplatin
• probenecid
• vaccines
Talk to your prescriber or health care professional before taking any of these medicines:
• aspirin
• acetaminophen
• ibuprofen
• naproxen
• ketoprofen
Tell your prescriber or health care professional about all other medicines you are taking, including nonprescription medicines, nutritional supplements, or herbal products. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.
What should I watch for while taking cisplatin?
Visit your prescriber or health care professional for checks on your progress. You will need to have regular blood checks. The side effects of cisplatin can continue after you finish your treatment; report side effects promptly.
After you receive cisplatin, it is important to drink lots of fluids for 1—2 days. This will help to decrease cisplatin's effects on your kidneys.
Cisplatin may make you feel generally unwell. This is because cisplatin affects good cells as well as cancer cells. Report any side effects as above, but continue your course of medicine even though you feel ill, unless your prescriber or health care professional tells you to stop.
In high doses or when given with other chemotherapy agents, cisplatin may decrease your body's ability to fight infections or increase your risk to bruise or bleed. Call your prescriber or health care professional if you have a fever, chills, sore throat or other symptoms of a cold or flu. Do not treat these symptoms yourself. Try to avoid being around people who are sick. Call your prescriber or health care professional if you notice any unusual bleeding. Be careful not to cut, bruise or injure yourself because you may get an infection and bleed more than usual.
Avoid taking aspirin, acetaminophen (Tylenol®), ibuprofen (Advil®), naproxen (Aleve®), or ketoprofen (Orudis® KT) products as these may hide a fever, unless instructed to by your prescriber or health care professional.
Call your prescriber or health care professional if you get diarrhea. Do not treat yourself.
Be careful brushing and flossing your teeth or using a toothpick while receiving cisplatin because you may get an infection or bleed more easily. If you have any dental work done, tell your dentist you are receiving cisplatin.
What side effects may I notice from receiving cisplatin?
The side effects you may experience with cisplatin therapy depend upon the dose, other types of chemotherapy or radiation therapy given, and the disease being treated. Not all of these effects occur in all patients. Discuss any concerns or questions with your prescriber or health care professional.
Side effects that you should report to your prescriber or health care professional as soon as possible:
• difficulty breathing, or wheezing
• hearing loss
• increase or decrease in the amount of urine passed, passing urine more often at night
• nausea and vomiting
• low blood counts - cisplatin may decrease the number of white blood cells, red blood cells and platelets. You may be at increased risk for infections and bleeding.
• symptoms of infection - fever or chills, cough, sore throat, pain or difficulty passing urine
• symptoms of decreased platelets or bleeding - bruising, pinpoint red spots on the skin, black, tarry stools, blood in the urine
• symptoms of decreased red blood cells (anemia) - unusual weakness or tiredness, fainting spells, lightheadedness
• pain or difficulty passing urine
• pain, swelling, redness or irritation at the injection site
• ringing in the ears
• swelling of the face
• tingling, pain or numbness in the hands or feet
Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):
• blurred vision, changes in eyesight
• changes in taste (like metallic taste or loss of taste)
• loss of appetite
Where can I keep my medicine?
This medicine is given in a hospital or clinic. You will not have to take this medicine at home.
Last updated: 7/1/2002
Important Disclaimer: The drug information provided here is for educational purposes only. It is intended to supplement, not substitute for, the diagnosis, treatment and advice of a medical professional. This drug information does not cover all possible uses, precautions, side effects and interactions. It should not be construed to indicate that this or any drug is safe for you. Consult your medical professional for guidance before using any prescription or over the counter drugs.
Wikipedia:
cisplatin
 |
|
 |
|
|
Cisplatin
|
|
| Systematic (IUPAC) name | |
| cis-diamminedichloroplatinum(II) | |
| Identifiers | |
| CAS number | |
| ATC code | L01 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | H6Cl2N2Pt |
| Mol. mass | 300.05 g/mol |
| Pharmacokinetic data | |
| Bioavailability | complete |
| Protein binding | > 90% |
| Metabolism | ? |
| Half life | 30-100 hours |
| Excretion | Renal |
| Therapeutic considerations | |
| Pregnancy cat. |
D(US) |
| Legal status | |
| Routes | Intravenous |
Cisplatin, cisplatinum or cis-diamminedichloroplatinum(II) (CDDP) is a platinum-based chemotherapy drug used to treat various types of cancers, including sarcomas, some carcinomas (e.g. small cell lung cancer, and ovarian cancer), lymphomas and germ cell tumors. It was the first member of its class, which now also includes carboplatin and oxaliplatin.
Pharmacology
Upon administration, a chloride ligand undergo slow displacement with water (an aqua ligand) molecules, in a process termed aquation. The aqua ligand in the resulting [PtCl(H2O)(NH3)2]+ is easily displaced, allowing cisplatin to coordinate a basic site in DNA. Subsequently, the platinum cross-links two bases via displacement of the other chloride ligand.[1] Cisplatin crosslinks DNA in several different ways, interfering with cell division by mitosis. The damaged DNA elicits DNA repair mechanisms, which in turn activate apoptosis when repair proves impossible.
Most notable among the DNA changes are the 1,2-intrastrand cross-links with purine bases. These include 1,2-intrastrand d(GpG) adducts which form nearly 90% of the adducts and the less common 1,2-intrastrand d(ApG) adducts. 1,3-intrastrand d(GpXpG) adducts occur but are readily excised by the nucleotide excision repair (NER) . Other adducts include inter-strand crosslinks and nonfunctional adducts that have been postulated to contribute to cisplatin's activity. Interaction with cellular proteins, particularly HMG domain proteins, has also been advanced as a mechanism of interfering with mitosis, although this is probably not its primary method of action.
trans-PtCl2(NH3)2
The trans-[PtCl2(H2O)(NH3)2 does not exhibit a comparably useful pharmacological effect. Its low activity is generally thought to be due to rapid deactivation of the drug before it can arrive at the DNA.[citation needed] It is toxic, and it is desirable to test batches of cis-platin for the absence of the trans isomer. In a procedure by Woollins et al., which is based on the classic 'Kurnakov test', thiourea reacts with the sample to give derivatives are easily separated and detected by HPLC.[2]
Side effects
Cisplatin has a number of side-effects that can limit its use:
- Nephrotoxicity (kidney damage) is a major concern when cisplatin is given. The dose is reduced when the patient's creatinine clearance (a measure of renal function) is reduced. Adequate hydration and diuresis is used to prevent renal damage. The nephrotoxicity of platinum-class drugs seems to be related to reactive oxygen species and in animal models can be ameliorated by free radical scavenging agents. This is a dose-limiting toxicity.
- Neurotoxicity (nerve damage) can be anticipated by performing nerve conduction studies before and after treatment.
Nausea and vomiting. Cisplatin is one of the most emetogenic chemotherapy agents, but this is managed with prophylactic antiemetics (e.g. ondansetron, granisetron, etc.) in combination with corticosteroids. Aprepitant combined with ondansetron and dexamethasone has been shown to be better for highly emetogenic chemotherapy than just ondansetron and dexamethasone.- Ototoxicity (hearing loss): unfortunately there is at present no effective treatment to prevent this side effect, which may be severe. Audiometric analysis may be necessary to assess the severity of ototoxicity. Other drugs (such as the aminoglycoside antibiotic class) may also cause ototoxicity, and the administration of this class of antibiotics in patients receiving cisplatin is generally avoided. The ototoxicity of both the aminoglycosides and cisplatin may be related to their ability to bind to melanin in the stria vascularis of the inner ear or the generation of reactive oxygen species.
- Alopecia (hair loss): this is generally not a major problem in patients treated with cisplatin.
- Electrolyte disturbance: Cisplatin can cause hypomagnesaemia, hypokalaemia and hypocalcaemia. The hypocalcaemia seems to occur in those with low serum magnesium secondary to cisplatin, so it is not primarily due to the Cisplatin.
History
The compound cis-PtCl2(NH3)2 was first described by M. Peyrone in 1845 (known as Peyrone's salt).[3] The structure was deduced by Alfred Werner in 1893.[1] In the 1960s, Barnett Rosenberg and van Camp et al at Michigan State University discovered that electrolysis of a platinum electrode produced cisplatin, which inhibited binary fission in Escherichia coli (E. coli) bacteria. The bacteria grow to 300 times their normal length but cell division fails. Rosenberg then conducted a series of experiments to test the effects various platinum coordination complexes on sarcomas artificially implanted in rats. This study found that cis-diamminedichloroplatinum(II) was the most effective out of this group, which started the medicinal career of cisplatin.[4]
Approved for clinical use by the United States Food and Drug Administration (FDA) in 1978,[citation needed] it revolutionized the treatment of certain cancers. Detailed studies on its molecular mechanism of action, using a variety of spectrocopic methods including X-ray, NMR spectroscopy, and other physico-chemical methods, revealed its ability to form irreversible crosslinks with bases in DNA.
Synthesis
The synthesis of cisplatin is a classic in inorganic chemistry. Starting from potassium tetrachloroplatinate, K2PtCl42−, the first NH3 ligand is added to any of the four equivalent positions, but the second NH3 could be added cis or trans to the amine ligand. Because Cl− has a larger trans effect than NH3, the second amine substitutes trans to a chloride ligand, and therefore cis to the first amine. The trans effect of the halides follows the order I->Br->Cl-, therefore the synthesis is conducted using PtI42− to ensure high yield and purity of the cis isomer, followed by conversion of the PtI2(NH3)2 into PtCl2(NH3)2, as first described by Dhara.[5][6]
References
- ^ a b
- ^ J. D. Woollins, A. Woollins and B. Rosenberg (1983). "The detection of trace amounts of trans-Pt(NH3)2Cl2 in the presence of cis-Pt(NH3)2Cl2. A high performance liquid chromatographic application of kurnakow's test". Polyhedron 2 (3): 175-178. DOI:10.1016/S0277-5387(00)83954-6.
- ^ Peyrone M. Ann Chemie Pharm 1845;51:129.
- ^ Rosenberg, B.; Van Camp, L.; Krigas, T. (1965). "Inhibition of cell division in Escherichia coli by electrolysis products from a platinum electrode". Nature 205 (4972): 698-699. DOI:10.1038/205698a0.
- ^ Dhara, S. C. Indian Journal of Chemistry 1970, volume 8, pp. 193–134.
- ^ Rebecca A. Alderden, Matthew D. Hall, and Trevor W. Hambley (2006). "The Discovery and Development of Cisplatin". J. Chem. Ed. 83: 728-724.
External links
- Cisplatin: The Invention of an Anticancer Drug by Andri Smith
- [http://www2.mrc-lmb.cam.ac.uk/personal/sl/Html/Frames.html Cisplatin and its Analogues (excellent detailed overview)
- MedlinePlus page on cisplatin
- IARC Monograph: "Cisplatin"
This entry is from Wikipedia, the leading user-contributed encyclopedia. It may not have been reviewed by professional editors (see full disclaimer)
Join the WikiAnswers Q&A community. Post a question or answer questions about "cisplatin" at WikiAnswers.
Copyrights:
 |
 | Dictionary. The American Heritage® Dictionary of the English Language, Fourth Edition Copyright © 2007, 2000 by Houghton Mifflin Company. Updated in 2007. Published by Houghton Mifflin Company. All rights reserved. Read more |
 |
| Oncology Encyclopedia. Gale Encyclopedia of Cancer. Copyright © 2006 by The Gale Group, Inc. All rights reserved. Read more |
 |
| Dental Dictionary. Mosby's Dental Dictionary. Copyright © 2004 by Elsevier, Inc. All rights reserved. Read more |
 |
| Drug Info. Gold Standard. Copyright © 2008 by Gold Standard. All rights reserved. Read more |
 |
| Wikipedia. This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Cisplatin". Read more |
Search for answers directly from your browser with the FREE Answers.com Toolbar!
Click here to download now. 
Get Answers your way! Check out all our free tools and products.
ADVERTISEMENT
Tackle These
Keep Reading
Mentioned In:
ADVERTISEMENT
Do you have the answers?
ADVERTISEMENT
