Any of a group of antibiotics produced by the soil actinomycete Streptomyces caespitosus that inhibit DNA synthesis and are used against bacteria and cancerous tumor cells.
[Probably MITO(SIS) + -MYCIN.]
mitomycin
Dictionary:
mi·to·my·cin (mī'tə-mī'sĭn)  |
| 5min Related Video: Mutamycin |
| Oncology Encyclopedia: Mitomycin-C |
Key Terms: Antineoplastic, Salvage therapy.
Definition
Mitomycin-C is also known as mitomycin and MMC. It is an antineoplastic, or medicine that kills cancer cells. It is sold under the trade name Mutamycin.
Purpose
Mitomycin-C may be used to fight a number of different cancers, including cancer of the stomach, colon, rectum, pancreas, breast, lung, uterus, cervix, bladder, head, neck, eye, and esophagus.
It is impossible to provide a detailed description of how mitomycin-C may be combined with other medications in the treatment of each of these cancers, but some examples can be presented. In the treatment of non-small cell lung cancer (NSCLC), one therapeutic regimen that may be used is known as MT, which consists of mitomycin-C, vindesine, and cisplatin.
Mitomycin-C is sometimes used in patients with colorectal cancer metastatic to the liver. However, the side effects of mitomycin-C, especially those involving the bone marrow and fatigue, are so great that other medications may be tried first. In treating breast cancer metastatic to the liver, mitomycin is regarded as salvage therapy as of the early 2000s.
For advanced stomach cancer, the FAM regimen may be used, which consists of fluorouracil, doxorubicin (adriamycin), and mitomycin-C. Mitomycin-C may also be used for colorectal cancer metastatic to the liver in combination with other medicines.
More recently, mitomycin has been found effective in treating malignant melanoma of the eye.
In addition to cancer treatment, mitomycin is sometimes used as a topical application in eye surgery to prevent visual haze after operations on the cornea (the transparent exterior coat that covers the front of the eye where light enters). It is also used topically by some doctors to keep incisions in the ear drum open in children with recurrent ear infections without the need to place ventilation tubes in the incisions. This use of mitomycin is considered experiental as of 2005.
Description
Mitomycin-C is an antitumor antibiotic. Mechanistically however, it belongs to DNA covalent binding (alkylating) agents. Mitomycin-C, upon bioactivation, kills cancer cells by disrupting the activity of DNA within the cells. DNA is an acid that contains genetic material.
Recommended Dosage
Twenty milligrams per square meter should be given intravenously every six to eight weeks when this medication is used alone. Alternately, five to ten milligrams per square meter may be given every six weeks when the drug is used in combination with other drugs. Mitomycin-C, leucovorin, and fluorouracil may be used to treat metastatic rectal cancer; this regimen includes an injection of 10 milligrams per square meter of mitomycin-C. When mitomycin-C is combined with vindesine and cisplatin in the treatment of non-small cell lung cancer, eight milligrams per square inch are administered intravenously on days one and twenty-nine of a six-week cycle.
Precautions
Because of the side effects associated with mitomycin-C, some physicians perform blood tests and order chest x rays (of the lungs) for patients receiving this therapy. The likelihood that lung problems will appear in patients receiving mitomycin-C increases if oxygen therapy and/or x-ray therapy are administered.
Patients receiving less than 60 mg of mitomycin-C are at reduced risk of developing a complex medical condition called cancer-associated hemolytic uremia syndrome (HUS). HUS is characterized by anemia, other blood defects, and kidney problems. Doctors should carefully observe patients receiving mitomycin-C, as cancer-related HUS is best treated early. However, HUS is not likely to develop until four or more months after the patient received the final dose of mitomycin-C. To achieve early diagnosis of HUS, the doctor may carefully monitor kidney function and blood levels. In addition, transfusions may be avoided as may be certain other procedures involving the blood, as these may increase the risk HUS will develop.
Side Effects
The ability of the bone marrow to produce blood cells may be affected. This side effect can be serious. If it occurs, the doctor may decide to reduce the dose of medicine administered. However, mitomycin-C may cause delayed, rather than immediate, bone marrow suppression. Once such suppression does occur it may last for as many as eight weeks.
Major lung problems may occur. Such lung deficits may start as no more than cough, fatigue, and breathing problems. Doctors may conduct lung function tests and obtain x rays to observe whether lung problems are developing. If these lung problems do occur, corticosteroids may provide effective therapy. Stopping mitomycin-C therapy may also be recommended.
Mitomycin-C may also cause cancer-associated HUS.
In addition, there may be nausea and vomiting, loss of appetite (anorexia), stomach problems, fatigue, fever, hair loss (alopecia), and lung problems. If bleeding does occur, there may be damage to the surrounding skin.
Resources
Books
Wilson, Billie A., Margaret T. Shannon, and Carolyn L. Stang. Nurses Drug Guide 2000. Stamford, CT: Appleton & Lange, 2000.
Periodicals
Brownstein, S. "Malignant Melanoma of the Conjunctiva." Cancer Control 11 (September-October 2004): 310–316.
d'Eredita, R. "Contact Diode Laser Myringotomy and Mitomycin C in Children." Otolaryngology and Head and Neck Surgery 130 (June 2004): 742–746.
Hashemi, H., S. M. Taheri, A. Fotouhi, and A. Kheiltash. "Evaluation of the Prophylactic Use of Mitomycin-C to Inhibit Haze Formation after Photorefractive Keratectomy in High Myopia: A Prospective Clinical Study." BMC Ophthalmology 4 (September 14, 2004): 12.
Loibl, S., G. von Minckwitz, K. Schwedler, et al. "Mitomycin C, 5-Fluorouracil and Folinic acid (Mi-Fu-Fo) as Salvage Chemotherapy in Breast Cancer Patients with Liver Metastases and Impaired Hepatic Function: A Phase II Study." Anti-Cancer Drugs 15 (August 2004): 719–724.
Rao, S., D. Cunningham, T. Price, et al. "Phase II Study of Capecitabine and Mitomycin C as First-Line Treatment in Patients with Advanced Colorectal Cancer." British Journal of Cancer 91 (August 31, 2004): 839–843.
Solomon, R., E. D. Donnenfeld, J. Thimons, et al. "Hyperopic Photorefractive Keratectomy with Adjunctive Topical Mitomycin C for Refractive Error after Penetrating Keratoplasty for Keratoconus." Eye and Contact Lens 30 (July 2004): 156–158.
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.
—Bob Kirsch; Rebecca J. Frey, PhD
| Drug Info: Mitomycin |
Brand names: Mitozytrex™Mutamycin®
Chemical formula:
- Drug Forms:
- Mitomycin injection (below)
- Mitomycin Solution for injection
Mitomycin injection
What is mitomycin injection?
MITOMYCIN (Mutamycin®, Mitozytrex™) is a chemotherapy agent used for treating various types cancer, including stomach, pancreas, bladder, breast, or lung cancer. Mitomycin interferes with the growth of rapidly dividing cells, like cancer cells, and eventually causes these cells to die. Mitomycin may be used alone or with other chemotherapy agents or radiation therapy. Generic mitomycin injection is 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
• anemia
• blood or bleeding disorders
• kidney disease
• previous radiation therapy
• an unusual or allergic reaction to mitomycin, other chemotherapy agents, other medicines, foods, dyes, or preservatives
• pregnant or trying to get pregnant
• breast-feeding
How should I use this medicine?
Mitomycin is for injection into a vein. It is usually administered in a hospital or clinic setting by a specially trained health care professional. Usually, you receive a dose once every 6—8 weeks depending upon your laboratory results and other medicines or treatments you are also receiving at the same time.
What if I miss a dose?
It is important not to miss a dose. Let your prescriber or health care professional know if you are unable to keep an appointment.What drug(s) may interact with mitomycin?
• in general, other chemotherapy agents may increase the side effects seen with mitomycin
• vaccines
• vinblastine, vincristine, or vinorelbine
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 mitomycin?
Visit your prescriber or health care professional for regular checks on your progress. You will need to have regular blood checks.
Mitomycin may make you feel generally unwell. This is not uncommon because mitomycin 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. After receiving mitomycin, you may feel lethargic or weak for several days up to as long as several weeks.
Mitomycin may decrease your body's ability to fight infections. 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. Mitomycin may increase your risk to bruise or bleed. 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 otherwise instructed by your prescriber or health care professional.
Be careful brushing and flossing your teeth or using a toothpick while receiving this drug because you may get an infection or bleed more easily. If you have any dental work done, tell your dentist you are receiving mitomycin.
If you are going to have surgery, tell your prescriber or health care professional that you are receiving mitomycin.
What side effects may I notice from receiving mitomycin?
The side effects you may experience with mitomycin 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:
• low blood counts - mitomycin may decrease the number of white blood cells, red blood cells and platelets. You may be at increased risk for infections and bleeding.
• 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, blood in the urine
• signs of decreased red blood cells - unusual weakness or tiredness, fainting spells, lightheadedness
• mouth or throat sores or ulcers
• non-productive cough, coughing up blood, or shortness of breath
• pain, redness, swelling or irritation at the injection site
Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):
• confusion
• diarrhea
• green to blue color of urine
• fatigue
• hair loss
• lethargy
• loss of appetite
• nail discoloration (purple-colored bands in the nail beds)
• nausea, vomiting
• mouth sores or ulcers
• tingling, pain or numbness
• weakness
Where can I keep my medicine?
This does not apply. You will not 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: Mitomycin |
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Mitomycin
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| Systematic (IUPAC) name | |
| [(1aS,8S,8aR,8bS)-6-amino-8a-methoxy-5-methyl-4,7-dioxo-1,1a,2,4,7,8,8a,8b-octahydroazireno[2',3':3,4]pyrrolo[1,2-a]indol-8-yl]methyl carbamate | |
| Identifiers | |
| CAS number | 50-07-7 |
| ATC code | L01DC03 |
| PubChem | 5746 |
| DrugBank | APRD00284 |
| Chemical data | |
| Formula | C15H18N4O5 |
| Mol. mass | 334.327 g/mol |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Metabolism | Hepatic |
| Half life | 8-48 min |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. | |
| Legal status | |
| Routes | [Intravenous therapy |
The mitomycins are a family of aziridine-containing natural products isolated from Streptomyces caespitosus or Streptomyces lavendulae.[1] One of these compounds, mitomycin C, finds use as a chemotherapeutic agent by virtue of its antitumour antibiotic activity. It is given intravenously to treat upper gastro-intestinal (e.g. esophageal carcinoma) and breast cancers, as well as by bladder instillation for superficial bladder tumours. It causes delayed bone marrow toxicity and therefore it is usually administered at 6-weekly intervals. Prolonged use may result in permanent bone-marrow damage. It may also cause lung fibrosis and renal damage.
Mitomycin C has also been used topically rather than intravenously in several areas. The first is cancers, particularly bladder cancers and intraperitoneal tumours.It is now well known that a single instillation of this agent within 6 hours of bladder tumor resection can prevent recurrence. The second is in eye surgery and the third is in esophageal and tracheal stenosis where application of mitomycin C onto the mucosa immediately following dilatation will decrease re-stenosis by decreasing the production of fibroblasts and scar tissue...
Mechanism of Action
Mitomycin C is a potent DNA crosslinker. A single crosslink per genome has shown to be effective in killing bacteria. This is accomplished by reductive activation followed by two N-alkylations. Both alkylations are sequence specific for a guanine nucleoside in the sequence 5'-CpG-3'.[2] Potential bis-alkylating heterocylic quinones were synthetised in order to explore their antitumoral activities by bioreductive alkylation.[3]
Biosynthesis
In general the biosynthesis of all mitomycins [4] proceed via combination of 3-amino-5-hydroxybenzoic acid (AHBA), D-glucosamine, and carbamoyl phosphate, to form the mitosane core, followed by specific tailoring steps. The key intermediate, AHBA, is a common precursor to other anticancer drugs, such as rifamycin and ansamycin.
Specifically, the biosynthesis begins with the addition of phosphoenolpyruvate (PEP) to erythrose-4-phosphate (E4P) with a yet undiscovered enzyme, which is then ammoniated to give 4-amino-3-deoxy-D-arabino heptulosonic acid-7-phosphate (aminoDHAP). Next, DHQ synthase catalyzes a ring closure to give 4-amino3-dehydroquinate (aminoDHQ), which is then undergoes a double oxidation via aminoDHQ dehydratase to give 4-amino-dehydroshikimate (aminoDHS). The key intermediate, 3-amino-5-hydroxybenzoic acid (AHBA), is made via aromatization by AHBA synthase.
Synthesis of the key intermediate, 3-amino-5-hydroxy-benzoic acid.
The mitosane core is synthesized as shown below via condensation of AHBA and D-glucosamine, although no specific enzyme has been characterized that mediates this transformation. Once this condensation has occurred, the mitosane core is tailored by a variety of enzymes. Unfortunately, both the sequence and the identity of these steps are yet to be determined.
- Complete reduction of C-6 - Likely via F420-dependent tetrahydromethanopterin (H4MPT)) reductase and H4MPT:CoM methyltransferase
- Hydroxylation of C-5, C-7 (followed by transamination), and C-9a. - Likely via cytochrome P450 monooxygenase or benzoate hydroxylase
- O-Methylation at C-9a - Likely via SAM dependent methyltransferase
- Oxidation at C-5 and C8 - Unknown
- Intramolecular amination to form aziridine - Unknown
- Carbamoylation at C-10 - Carbamoyl transferrase, with carbamoyl phosphate (C4P) being derived from L-citrulline or L-arginine
Formation of mitosane core followed by tailoring specific to Mitomycin C.
References
- ^ Danshiitsoodol N, de Pinho CA, Matoba Y, Kumagai T, Sugiyama M (2006). "The mitomycin C (MMC)-binding protein from MMC-producing microorganisms protects from the lethal effect of bleomycin: crystallographic analysis to elucidate the binding mode of the antibiotic to the protein". J Molec Biol 360 (2): 398–408. doi:.
- ^ Tomasz, Maria (September 1995). "Mitomycin C: small, fast and deadly (but very selective).". Chemistry and Biology 2 (9): 575–579. doi:.
- ^ Renault, J.;Baron, M; Mailliet P. & al. Heterocyclic quinones.2.Quinoxaline-5,6-(and 5-8)-diones - Potential antitumoral agents. Eur. J. Med. Chem. 16, 6, 545-550, 1981.
- ^ Mao Y.; Varoglu M.; Sherman D.H. (April 1999). "Molecular characterization and analysis of the biosynthetic gene cluster for the antitumor antibiotic mitomycin C from Streptomyces Iavendulae NRRL 2564.". Chemistry and Biology 6 (4): 251–263. doi:.
- Hata, T.; Sano, Y.; Sugawara, R.; Matsumae, A.; Kanamori, K.; Shima, T.; Hoshi, T. J. Antibiot. Ser. A 1956, 9, 141-146.
- Fukuyama, T.; Yang, L. "Total Synthesis of (±)-Mitomycins via Isomitomycin A." J. Am. Chem. Soc. 1987, 109, 7881-7882.
- Mao, Y.; Varoglu, M.; Sherman, D.H. "Molecular characterization and analysis of the biosynthetic cluster for the antitumor antibiotic mitomycin C from Streptomyces lavendulae NRRL 2564." Chemistry & Biology 1999, 6, 251-263.
- Varoglu, M.; Mao, Y.; Sherman, D.H. "Mapping the Biosynthetic Pathway by Functional Analysis of the MitM Aziridine N-Methyltransferase." J. Am. Chem. Soc. 2001, 123, 6712-6713 and references therein.
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 | Dictionary. The American Heritage® Dictionary of the English Language, Fourth Edition Copyright © 2007, 2000 by Houghton Mifflin Company. Updated in 2009. Published by Houghton Mifflin Company. All rights reserved. Read more |
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| Oncology Encyclopedia. Gale Encyclopedia of Cancer. Copyright © 2006 by The Gale Group, Inc. All rights reserved. Read more |
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