(medicine) A platinum coordination compound and anticancer agent used for advanced gynecologic malignancies, especially ovarian tumors, and for head and neck cancers and lung cancers.
Carboplatin
| Sci-Tech Dictionary: carboplatin |
(¦kär·bō′plat·ən)
| 5min Related Video: Carboplatin |
| Oncology Encyclopedia: Carboplatin |
Key Terms: Anemia, Apoptosis, Chemotherapy, DNA, Electrolytes, Food and Drug Administration, Intravenous, Leukopenia, Metastatic.
Definition
Carboplatin is a chemotherapeutic agent used to treat cancer by interfering with the growth of cancer cells. At the molecular level, carboplatin causes cancer cells to destroy themselves through the mechanism of apoptosis. Carboplatin is marketed under the brand name Paraplatin; it may also be referred to as CBDCA, JM-8, or carboplatinum.
Purpose
Carboplatin was approved in 1989 by the Food and Drug Administration (FDA) for the palliative treatment of ovarian cancer. The term palliative means that the treatment is not intended to cure but only to relieve symptoms. Carboplatin has also been used to treat other types of cancer, including head and neck cancer, cervical cancer, lung cancer, endometrial cancer, testicular cancer, hormone-refractory prostate cancer, and brain tumors.
More recently, carboplatin has been investigated in clinical trials as a possible treatment for squamous cell skin cancers and malignant melanoma.
Description
Carboplatin is a member of the group of chemotherapy drugs known as heavy metal-like alkylating agents. Alkylating agents interfere with the genetic material (deoxyribonucleic acid, or DNA) inside the cancer cells and prevent them from further dividing and growing more cancer cells.
Recommended Dosage
The dose of carboplatin can be calculated using several methods. A carboplatin dose can be determined using a mathematical calculation that measures a person's body surface area (BSA). This number is dependent upon a patient's height and weight: the larger the person, the greater the body surface area. BSA is measured by the square meter (m2). The body surface area is calculated and then multiplied by the drug dosage in milligrams per square meter (mg/m2). This calculates the actual dose a patient is to receive.
A common dosage of carboplatin alone for the treatment of patients with recurrent ovarian cancer is 360 mg/m2 given on day one into a vein every four weeks. When given in combination with the chemotherapeutic agent cyclophosphamide for the treatment of recurrent ovarian cancer, a dose of 300 mg/m2 administered intravenously is typical. This combination is repeated every four weeks for six cycles.
The second way to determine the dose of carboplatin is for the physician to measure or estimate how well the patient's kidneys work. The patient may be asked to collect all of their urine in a bottle for a 24-hour period. The sample will then be sent to a laboratory and analyzed. A mathematical calculation is performed to determine how well the patient's kidneys are working and subsequently to determine the carboplatin dose.
Precautions
Blood counts will be monitored regularly while on carboplatin therapy. During a certain time period after receiving carboplatin there is an increased risk of getting infections. Caution should be taken to avoid unnecessary exposure to infectious agents. Patients should also check with their doctors before receiving live virus vaccines while on chemotherapy.
Patients who may be pregnant or trying to become pregnant should talk to their doctor before receiving carboplatin. Men and women undergoing chemotherapy are at risk of becoming sterile.
Patients with known previous allergic reactions to chemotherapy drugs should notify their doctors.
Side Effects
Most of the side effects of carboplatin are due to its induction of apoptosis in tumor cells. Nausea and vomiting are among the most common side effects from receiving carboplatin. Nausea and vomiting can begin up to six hours after treatment and can last as long as 24 hours. Patients are given medicines known as antiemetics before receiving carboplatin to help prevent or decrease this side effect. Diarrhea, loss of appetite, constipation, pain, and weakness have also been reported to occur.
Myelosuppression, or a suppression of bone marrow activity resulting in a low blood cell count, is expected to occur following carboplatin administration. When a patient's white blood cell count drops below normal (leukopenia), there is an increased risk of developing a fever and infections. Neupogen, a drug used to increase the white blood cell count, may be administered.
A decrease in platelet count is most notable following carboplatin administration. Platelets are blood cells that aid for the formation of clots. When the platelet count becomes abnormally low, patients are at an increased risk for bruising and bleeding. If the platelet count remains too low a platelet blood transfusion is an option. Low red blood cell counts (anemia) may also occur following many cycles of carboplatin administration; during the first cycles this is usually not a common problem. Low red blood cell counts may result in dizziness and fatigue and can be treated with the drug erythropoietin.
A less common side effect of carboplatin is damage to nerves and nervous system tissues. Patients may feel tingling and numbness of the fingers and toes. This side effect is more common in patients over 65 years of age or those who have previously received the chemotherapy drug cisplatin. Other less common side effects include rash, itching, hairloss(alopecia), mouth sores, hearing problems, kidney problems, liver problems, vision problems, swelling, redness and pain at the site of injection, allergic reactions, heart problems, and breathing problems.
Carboplatin may cause the body to waste certain normal electrolytes that circulate in the body. Low levels of magnesium, calcium, phosphate, or sodium can be found in patients who have received carboplatin. These rarely cause difficulties and are monitored by the doctor.
Some patients develop hypersensitivity or allergic reactions to carboplatin that may include difficulty breathing, rash, itching, redness in the face, dizziness, an increased heart rate, and a drop in blood pressure. The risk of such reactions is increased in patients who have had more than six cycles of treatment with the drug. A group of researchers in Ohio has developed a skin test to evaluate patients for possible hypersensitivity reactions to carboplatin, and a second team is working on a desensitization regimen that will allow patients who have become hypersensitive to the drug to continue to benefit from treatment with it.
Interactions
Patients being treated with carboplatin should avoid other drugs that may cause damage to the kidneys or hearing.
Resources
Periodicals
Boulikas, T., and M. Vougiouka. "Cisplatin and Platinum Drugs at the Molecular Level." Oncology Reports 10 (November-December 2003): 1663–1682.
Markman, M., K. Zanotti, G. Peterson, et al. "Expanded Experience with an Intradermal Skin Test to Predict for the Presence or Absence of Carboplatin Hypersensitivity." Journal of Clinical Oncology 21 (December 15, 2003): 4611–4614.
Markman, M. "Toxicities of the Platinum Antineoplastic Agents." Expert Opinion on Drug Safety 2 (November 2003): 597–607.
McElroy, T. M., V. E. Gruenigen, and S. E. Waggoner. "A Case of Prolonged Carboplatin Therapy in a Patient with Carboplatin Hypersensitivity." Gynecologic Oncology 91 (November 2003): 435–437.
Moosman, P., F. Egli, R. A. Stahel, and L. Jost. "Weekly Paclitaxel and Carboplatin Combination Chemotherapy in Patients with Advanced Squamous Cell Carcinoma of the Head and Neck." Onkologie 26 (December 2003): 568–572.
Oh, W. K., S. Halabi, W. K. Kelly, et al. "A Phase II study of Estramustine, Docetaxel, and Carboplatin with Granulocyte-Colony-Stimulating Factor Support in Patients with Hormone-Refractory Prostate Carcinoma: Cancer and Leukemia Group B 99813." Cancer 98 (December 15, 2003): 2592–2598.
Strauss, S. J., M. Marples, M. P. Napier, et al. "A Phase I (Tumour Site-Specific) Study of Carboplatin and Temozolomide in Patients with Advanced Melanoma." British Journal of Cancer 89 (November 17, 2003): 1901–1905.
Organizations
United States Food and Drug Administration (FDA). 5600 Fishers Lane, Rockville, MD 20857-0001. (888) INFO-FDA (463-6332).
—Nancy J. Beaulieu, RPh., BCOP; Rebecca J. Frey, PhD
| Drug Info: Carboplatin |
Brand names: Paraplatin®
Chemical formula:
Carboplatin Solution for injection
What is this medicine?
CARBOPLATIN (KAR boe pla tin) is a chemotherapy drug. It targets fast dividing cells, like cancer cells, and causes these cells to die. This medicine is used to treat ovarian cancer and many other cancers.
This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.
What should I tell my health care provider before I take this medicine?
They need to know if you have any of these conditions:
•blood disorders
•hearing problems
•kidney disease
•recent or ongoing radiation therapy
•an unusual or allergic reaction to carboplatin, cisplatin, other chemotherapy, other medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding
How should I use this medicine?
This drug is usually given as an infusion into a vein. It is administered in a hospital or clinic by a specially trained health care professional.
Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed.
Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.
NOTE: This medicine is only for you. Do not share this medicine with others.
What may interact with this medicine?
•medicines for seizures
•medicines to increase blood counts like filgrastim, pegfilgrastim, sargramostim
•some antibiotics like amikacin, gentamicin, neomycin, streptomycin, tobramycin
•vaccines
Talk to your doctor or health care professional before taking any of these medicines:
•acetaminophen
•aspirin
•ibuprofen
•ketoprofen
•naproxen
This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.
What should I watch for while using this medicine?
Your condition will be monitored carefully while you are receiving this medicine. You will need important blood work done while you are taking this medicine.
This drug may make you feel generally unwell. This is not uncommon, as chemotherapy can affect healthy cells as well as cancer cells. Report any side effects. Continue your course of treatment even though you feel ill unless your doctor tells you to stop.
In some cases, you may be given additional medicines to help with side effects. Follow all directions for their use.
Call your doctor or health care professional for advice if you get a fever, chills or sore throat, or other symptoms of a cold or flu. Do not treat yourself. This drug decreases your body's ability to fight infections. Try to avoid being around people who are sick.
This medicine may increase your risk to bruise or bleed. Call your doctor or health care professional if you notice any unusual bleeding.
Be careful brushing and flossing your teeth or using a toothpick because you may get an infection or bleed more easily. If you have any dental work done, tell your dentist you are receiving this medicine.
Avoid taking products that contain aspirin, acetaminophen, ibuprofen, naproxen, or ketoprofen unless instructed by your doctor. These medicines may hide a fever.
Do not become pregnant while taking this medicine. Women should inform their doctor if they wish to become pregnant or think they might be pregnant. There is a potential for serious side effects to an unborn child. Talk to your health care professional or pharmacist for more information. Do not breast-feed an infant while taking this medicine.
What side effects may I notice from receiving this medicine?
Side effects that you should report to your doctor or health care professional as soon as possible:
•allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
•signs of infection - fever or chills, cough, sore throat, pain or difficulty passing urine
•signs of decreased platelets or bleeding - bruising, pinpoint red spots on the skin, black, tarry stools, nosebleeds
•signs of decreased red blood cells - unusually weak or tired, fainting spells, lightheadedness
•breathing problems
•changes in hearing
•changes in vision
•chest pain
•high blood pressure
•low blood counts - This drug may decrease the number of white blood cells, red blood cells and platelets. You may be at increased risk for infections and bleeding.
•nausea and vomiting
•pain, swelling, redness or irritation at the injection site
•pain, tingling, numbness in the hands or feet
•problems with balance, talking, walking
•trouble passing urine or change in the amount of urine
Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):
•hair loss
•loss of appetite
•metallic taste in the mouth or changes in taste
This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Where should I keep my medicine?
This drug is given in a hospital or clinic and will not be stored 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.
| Veterinary Dictionary: carboplatin |
A cisplatin analog, but with fewer side-effects. Under investigation in the treatment of cancer in dogs. Myelosuppression limits the dose that can be used.
| Wikipedia: Carboplatin |
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Carboplatin
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| Systematic (IUPAC) name | |
| azanide; cyclobutane-1,1-dicarboxylic acid; platinum | |
| Identifiers | |
| CAS number | 41575-94-4 |
| ATC code | L01XA02 |
| PubChem | 498142 |
| DrugBank | APRD00466 |
| Chemical data | |
| Formula | C6H14N2O4Pt |
| Mol. mass | 371.249 g/mol |
| Pharmacokinetic data | |
| Bioavailability | complete |
| Protein binding | Very low |
| Metabolism | ? |
| Half life | 1.1-2 hours |
| Excretion | hepatic |
| Therapeutic considerations | |
| Pregnancy cat. |
D(US) |
| Legal status |
Rx Only |
| Routes | Intravenous |
 (what is this?) (verify) |
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Carboplatin is a chemotherapy drug used against some forms of cancer (mainly ovarian carcinoma, lung, head and neck cancers). It was introduced in the late 1980s and has since gained popularity in clinical treatment due to its vastly reduced side-effects compared to its parent compound cisplatin. Cisplatin and carboplatin, as well as oxaliplatin, interact with DNA, akin to the mechanism of alkylating agents.
Contents |
History
Carboplatin was discovered 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.
Pharmacology
Chemistry
Carboplatin differs from cisplatin in that it has a bidentate dicarboxylate (CBDCA) ligand as its leaving group instead of the more labile chloride ligands. It exhibits lower reactivity and slower DNA binding kinetics, though 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. 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).
Mode of action
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 Pt2+ species.
Side-effects
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. Carboplatin has also proven effective in some strains of cancer that may not be susceptible to cisplatin, including germ-line cell, small and non-small cell lung, ovary, and bladder cancers, as well as acute leukemia.
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 readmission to hospital and treatment with antibiotics.
Relative to cisplatin, the potency of carboplatin is less potent: depending on the strain of cancer, carboplatin may only be 1/8 to 1/45 as effective. The clinical standard of dosage of carboplatin is usually a 4:1 ratio compared to cisplatin; that is, for a dose that usually requires a particular dose of cisplatin, four times more carboplatin is needed to achieve the same effectiveness. The stable property of carboplatin is a mixed blessing: once uptake of the drug occurs, its retention half-life is considerably longer than cisplatin, but it is also this inertness that causes carboplatin to go right through the human body, and up to 90% of the carboplatin given can be recovered in urine.
The effectiveness of carboplatin can be increased by first incubating carboplatin in a sodium chloride (NaCl) solution. After 24 hours, an analysis was performed on the solution by separating the compounds by thin-layer chromatography (TLC). The TLC isolated cisplatin, carboplatin, and several platinum by-products in the solution. Numerous trials were conducted, and the trend showed that the survival rate of E. coli dropped dramatically as the molarity of the NaCl incubating solution increased. The treated E. coli also showed decreased amounts of alkaline phosphatase, a protein indicator of cellular size. This suggests that as this incubated carboplatin solution was administered to cells, they began to shrink and eventually die; apparently by the same mechanism that cisplatin works.
GemCarbo chemotherapy for lung cancer
GemCarbo chemotherapy (consisting of gemcitabine, also known as Gemzar, and carboplatin which are both colourless fluids) is used to treat several different types of cancer, but is most commonly used to treat lung cancer.[1] GemCarbo chemotherapy is usually given as a day patient treatment, involving a blood test the day before, and the drugs are given by an infusion. The GemCarbo regimen is given as a 21-day cycle and on the first day of treatment the patient is given both the gemcitabine and carboplatin. On the same day of the following week (day eight) there is a drip of gemcitabine only. There then follows a rest period of two weeks which completes one cycle of chemotherapy. The next cycle of treatment is given after a rest period, which will be three weeks after the first injection. Usually 4–6 cycles of treatment are given over a period of 3–4 months and this makes up a course of treatment. This treatment may prevent the further spread of the cancer or in some cases may reduce the size of the tumor between 20%-80% depending upon the individual.
Current events
A recent study in mutant mice suggests that in the subset of women with breast cancer due to BRCA1 and BRCA2 genes (these cause a variety of familial breast cancer) carboplatin may be as much as 20 times more effective than the usual breast cancer treatments.[2] However, similar data in humans has not yet been shown.
Carboplatin has also been used to treat testicular cancer patients with stage 1 seminoma. Recent research indicates that this treatment is more effective and has fewer side effects than adjuvant radiotherapy.[3][4][5] It is as effective as radiotherapy at preventing development of seminoma in the remaining testicle.[6]
References
- ^ Macmillan GemCarbo chemotherapy
- ^ Mark Henderson, "Lung cancer drug may fight breast tumour in women", (May 1, 2006) Times Online http://www.timesonline.co.uk/tol/news/uk/article711744.ece
- ^ http://www.asco.org/ASCO/Abstracts+%26+Virtual+Meeting/Abstracts?&vmview=abst_detail_view&confID=55&abstractID=34426
- ^ http://news.bbc.co.uk/2/hi/health/4700755.stm
- ^ http://www.timesonline.co.uk/tol/life_and_style/health/article4887854.ece
- ^ http://www.medscape.com/viewarticle/575825
Additional references
- Natarajan, G., et al., Increased DNA-binding activity of carboplatin in the presence of nucleophiles and human breast cancer MCF-7 cell cytoplasmic extracts: activation theory revisited. Biochem. Pharmacol. 58, 1625-1629 (1999). PMID 10535754.
- Knox, RJ et al., Mechanism of cytotoxicity of anticancer platinum drugs: evidence that cis-diamminedichloroplatinum(II) and cis-diammine-(1,1-cyclobutanedicarboxylato)platinum(II) differ only in the kinetics of their interaction with DNA., Cancer Res. 1986 Apr;46 (4 Pt 2):1972-9. PMID 3512077
- Canetta R, Rozencweig M, Carter SK., Carboplatin: the clinical spectrum to date., Cancer Cancer Treat Rev. 1985 Sep;12 Suppl A:125-36. PMID 3002623
- Overbeck, T, et al. "A comparison of the genotoxic effects of carboplatin and cisplatin in Escherichia Coli". Mutation Research/DNA Repair. Volume: 362, Issue: 3, April 2, 1996, pp. 249-259
- Schnurr, B., Gust, Ronald. "Investigations on the decomposition of carboplatin in infusion solutions". Mikrochimica Acta. Volume: 140, Issue: 1-2, August, 2002, pp. 69 – 76
- Xiang, Wang. "Structural studies of atom-specific actions on DNA". Pharmacology & Therapeutics. Volume: 83, Issue: 3, September, 1999, pp. 181-215
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