

<b>Dacarbazine</b>


%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%

General Considerations

URLs for Patient Information 

Package Insert Type Information

Clinical Trial Results



%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%

<b>General Considerations</b>

Dacarbazine is a classic drug used for sarcomas.  It was often part of a cocktail like MAID or CYVADIC.  It is an intravenous drug, which is metabolized in the body to the active agents.  Temozolomide, a new drug, is closely related and is hydrolyzed to the same agents.  Temozolomide is an oral agent, however.

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

<b>URLs for Patient Information Online</b>


Dacarbazine   DTIC

http://www.cancerbackup.org.uk/info/dacarbazine.htm 

http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202178.html 

http://www.cancersource.com/Resources/drugguide/index.cfm?DiseaseID=1 

http://www.medscape.com/druginfo/search?search_text=dacarbazine&search_type=drug&submit.x=14&submit.y=6 


~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~`

<b>Package Insert Type Information</b>


Dacarbazine       Brand Names: DTIC-Dome, DIC, Imidazole carboxamide 
 
Dacarbazine is an alkylating agent 
It was initially developed as a purine antimetabolite but its antitumor activity is not mediated via inhibition of purine biosynthesis.  It is a prodrug, and must be metabolized to form the active agents.  This drug methylates nucleic acids and inhibits DNA, RNA, and protein synthesis. 

Resistance develops from increased activity of DNA repair enzymes such as O6-alkylguanine-DNA alkyltransferase (AGAT). 

  
 
Absorption by mouth is slow and varies...intravenous administration is preferred.
It is metabolized in the liver by the microsomal P450 system to active metabolites (MTIC, AIC). The elimination half-life of the drug is 5 hours. About 40-50% of the parent drug is excreted unchanged in urine within 6 hours.  Dose modification should be considered in patients with moderately severe hepatic and/or renal dysfunction.  The drug is distributed in body tissues and about 20% is loosely bound to plasma proteins.

One of its indications is for soft tissue sarcomas.

 Dose as a single agent, 250 mg/m2 IV for 5 days or 800-1000 mg/m2 IV every 3 weeks.  It is often used in cocktails, which decreases the dose.


The drug is available in 100 and 200 mg vials for intravenous use.  Add sterile water or 0.9% sodium chloride to vial. Avoid exposure to light. 
Reconstituted solution should be yellow and should be discarded if the solution turns pink or red. 

<b> BEWARE:</b>
Dacarbazine is a potent vesicant [it is corrosive], and it should be carefully administered to avoid the risk of extravasation [leaking into the tissues]. 

There should be use of aggressive antiemetics prior to drug administration to decrease risk of nausea and vomiting, because dacarbazine is highly emetogenic.
 
Patients should avoid sun exposure for several days after dacarbazine therapy.  Sun sensitivity develops. 

Do not fall pregnant, impregnate, be pregnant, or breast feed while taking this medicine.
 
 ~~~~~~~~~~~~~~~

<b>Drug Interactions.</b>


Heparin, lidocaine, and hydrocortisone are incompatible with dacarbazine. 
 
Both dilantin and phenobarbital induce dacarbazine metabolism by the liver P450 system.  This decreases the potency of dacarbazine. 
 
Interleukin-2 alters dacarbazine pharmacokinetics by increasing elimination by the kidneys. 

When receiving dacarbazine it is especially important that your doctor know if you are taking any of the following:  [Dacarbazine may increase the effects of these medicines]
 
  Amphotericin B by injection (e.g., Fungizone) or 
  Antithyroid agents (medicine for overactive thyroid) or 
  Azathioprine (e.g., Imuran) or 
  Chloramphenicol (e.g., Chloromycetin) or 
  Colchicine or 
  Flucytosine (e.g., Ancobon) or 
  Ganciclovir (e.g., Cytovene) or 
  Interferon (e.g., Intron A, Roferon-A) or 
  Plicamycin (e.g., Mithracin) or 
  Zidovudine (e.g., AZT, Retrovir) or 


~~~~~~~~~~~~~~~~

<b>Common Side Effects</b>

Although not all of these side effects may occur, if they do occur they may need medical attention.  Also, because of the way these medicines act on the body, there is a chance that they might cause other unwanted effects that may not occur until months or years after the medicine is used. These delayed effects may include certain types of cancer, such as leukemia. Discuss these possible effects with your doctor.

Myelosuppression. Dose-limiting toxicity. Leukopenia and thrombocytopenia are equally affected with nadir occurring at 21-25 days.   
Symptoms of black, tarry stools;  or blood in urine or stools; or cough or hoarseness, accompanied by fever or chills;  or fever or chills;  or lower back or side pain, accompanied by fever or chills;  or painful or difficult urination, accompanied by fever or chills;  pinpoint red spots on skin;  or unusual bleeding or bruising  can occur and are serious, and need attention.
Check with your doctor or nurse immediately if any of these side effects occur:

Nausea and vomiting can be severe, usually occurring within 1-3 hours and lasting for up to 12 hours. Aggressive antiemetic therapy is strongly recommended. Loss of appetite is common, but diarrhea occurs rarely. 
 
Flu-like syndrome in the form of fever, chills, malaise, myalgias, and arthralgias. May last for several days after therapy. Notify your doctor.
 
Redness, swelling, and pain and/or burning at the site of injection. If dacarbazine accidentally seeps out of the vein into which it is injected, it may damage some tissues and cause scarring. Tell the doctor or nurse right away if you notice redness, pain, or swelling at the place of injection.

CNS toxicity in the form of paresthesias, neuropathies, ataxia, lethargy, headache, confusion, and seizures have all been observed.  Notify your doctor.

Shortness of breath;  stomach pain;  swelling of face;  yellow eyes or skin  -- if you have any of these symptoms, Notify your doctor.
 
There is an ncreased risk of photosensitivity, stay out of the sun.
 
This drug is teratogenic, mutagenic, and carcinogenic. 

~~~~~~~~~~~~~~~~~~~~~~~

Before taking this drug, notify your doctor of any of the following:

If you are pregnant, breast feeding or planning children in the future, inform your doctor of this before treatment. This drug may cause birth defects if either the male or female is taking it at the time of conception or during pregnancy. Men and women who are taking this drug need to use some kind of birth control. However, do not use oral contraceptives ("the pill") without checking with your doctor.  Tell your doctor right away if you think you have become pregnant while receiving dacarbazine.

If you are thinking about wanting to have children in the future, be sure to discuss this with your doctor. Many chemotherapy drugs can cause sterility.  

If you have any of the following medical problems:
chickenpox or exposure to chickenpox, gout, heart disease, congestive heart failure, shingles,  infection,  kidney disease, kidney stones, liver disease.

Tell your doctor if you have ever had any unusual or allergic reaction to dacarbazine.

If you are taking any other prescription or over-the-counter drugs, including vitamins and herbals.

Should I avoid any other medications, foods, alcohol, and/or activities?
Your prescription and nonprescription medications may interact with other drugs, causing a harmful effect. Certain foods or alcohol can also interact with drug products. Never begin taking a new medication, prescription or nonprescription, without asking your doctor or nurse if it will interact with alcohol, foods or other medications. Some drug products can cause drowsiness and may affect activities such as driving. Your prescription and nonprescription medications may interact with other drugs, causing a harmful effect. Certain foods or alcohol can also interact with drug products. Never begin taking a new medication, prescription or nonprescription, without asking your doctor or nurse if it will interact with alcohol, foods or other medications. Some drug products can cause drowsiness and may affect activities such as driving.

Breast-feeding-It is not known whether dacarbazine passes into breast milk. However, because this medicine may cause serious side effects, breast-feeding is generally not recommended while you are receiving it.

Children-Studies on this medicine have been done only in adult patients and there is no specific information comparing use of dacarbazine in children with use in other age groups.

Older adults-Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults or if they cause different side effects or problems in older people. There is no specific information about the use of dacarbazine in the elderly.

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

Dosing-
The dose of dacarbazine will be different for different patients. The dose that is used may depend on a number of things, including what the medicine is being used for, the patient's weight, and whether or not other medicines are also being taken. If you are receiving dacarbazine at home, follow your doctor's orders or the directions on the label. If you have any questions about the proper dose of dacarbazine, ask your doctor.

Precautions While Using This Medicine

It is very important that your doctor check your progress at regular visits While you are being treated with dacarbazine, and after you stop treatment with it, do not have any immunizations (vaccinations) without your doctor's approval. Dacarbazine may lower your body's resistance and there is a chance you might get the infection the immunization is meant to prevent. In addition, other persons living in your household should not take oral polio vaccine since there is a chance they could pass the polio virus on to you. Also, avoid persons who have taken oral polio vaccine within the last several months. Do not get close to them, and do not stay in the same room with them for very long. If you cannot take these precautions, you should consider wearing a protective face mask that covers the nose and mouth. 

Dacarbazine can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. It can also lower the number of platelets, which are necessary for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding: 

If you can, avoid people with infections. 
Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills,   cough or hoarseness, lower back or side pain, or painful or difficult urination. 
Check with your doctor immediately if you notice any unusual bleeding or bruising; black, tarry stools; blood in urine or stools; or pinpoint red spots on your skin. 
Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done. 
Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime. 
Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail cutters. 
Avoid contact sports or other situations where bruising or injury could occur. 

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~


<b>Clinical Trial Results


The Clinical Trials results are the experiments done in the past to see if the drug works, and how well, and for how long. 


PubMed Searches
Directions for use:

When you click on the search string, it will connect you to Pubmed and display the first 20 citations [which they will call Summaries].  What you WANT is the complete listing of all the summaries of the article [which they will call Abstracts. ]  

Go to the second toolbar, and use the drop down menu to change summaries to Abstracts,  and 20 to 200,  and sort by DATE, and then click on DISPLAY on that same toolbar.  You may have to wait while the page loads.

NOW you can save this search to a folder on your hard drive as "Dacarbazine Clinical Trials" as an HTML file - or as a text file.  The entire file, or just those parts which you wish to discuss, can be printed out and taken to talk over with your doctor.</b>



Clinical trials and LMS and dacarbazine
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&db=PubMed&term=clinical%20trial%20AND%20leiomyosarcoma%20AND%dacarbazine%20NOT%20mesna  

Clinical trials and sarcoma and dacarbazine
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&db=PubMed&term=clinical%20trial%20AND%20sarcoma%20AND%dacarbazine%20NOT%20mesna  

Temozolomide and Dacarbazine
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&db=PubMed&term=temozolomide%20AND%20dacarbazine 





ASCO Searches

You will have to go to the site and search year by year with keywords of the chemotherapy agent AND sarcoma.
http://www.asco.org/ac/1,1003,_12-002328,00.asp 
http://www.asco.org/prof/me/html/01abstracts/toc.htm

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

compiled by doctordee

March 2003







