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Doxorubicin & Epirubicin [Adriamycin, Doxil, Epiadriamycin]
compiled by doctordee
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Some Considerations

Adriamycin, Doxil, and Epiadriamycin are three members of the class of chemotherapy agents called anthracyclines.

Adriamycin, and possibly to a lesser extent, Epiadriamycin, is very toxic to bone marrow and heart, and causes permanent damage. There is a lifetime limit to the amount you can have. The side effects are severe. Adriamycin is a chemotherapy agent developed in the 1970's, and it is generally used for very resistant cancers.
It is a first line, classic drug used for soft tissue sarcomas. During the pre-Gleevec years, GIST was included in the NON-uterine LMS statistics, which might account for a lowering of Adriamycin's response rate. GastroIntestinal Stromal Tumors are very difficult to treat. It is hard to know what Adriamycin's record with extremity or other LMS is, because of the confounding inclusion of GIST in the earlier studies.

Doxil is a new preparation of doxorubicin, liposomal doxorubicin. In an appropriate dose, it is supposedly equivalent to Adriamycin in effectiveness, but delivers much less toxicity to the normal tissues of the rest of the body. The side effect profile is likewise much less severe. It is still too new a drug to know about the cardiotoxicity, or the potency.

[Editorial comment. Understand that Doxil has not been in use for very long, and that there might be side effects or undesirable long term effects that have not yet been discovered. Doxil is currently more expensive than the other agents mentioned. Doxil must be taken in an adequate dosage for it to be equivalent to Adriamycin. Doxil is the safer and better tolerated drug so far as we know to date, but we do not know if it is clinically as powerful as doxorubicin in treating LMS.]

EpiAdriamycin is an agent very similar to Adriamycin, used in similar circumstances. It is believed to have less cardiac toxicity than Adriamycin, but likewise has a lifetime limit because of cardiac toxicity.

The Clinical Trial Results further below are the abstracts of Clinical Trials of doxorubicin [Adriamycin] and its related compounds either alone or with other chemotherapy agents, when the trials included leiomyosarcomas among the patients' tumors.

URLs for Patient Information
Doxorubicin [Adriamycin]
Epidoxorubicin [Epiadriamycin]
Liposomal Doxorubicin [Doxil]


doxorubicin - Adriamycin

CancerBacup Drug Information

MedlinePlus Information

Medscape Drug Information. Registration is free.

CancerSource Drug Information



epirubicin - Epiadriamycin

CancerBacup Drug Information

MedlinePlus Information

Medscape Drug Information. Registration is free.

CancerSource Drug Information



liposomal doxorubicin - Doxil

CancerBacup Drug Information

MedlinePlus Drug Information

CancerSource Drug Information

General Information on Doxorubicin

Adriamycin

Doxorubicin hydrochloride, or Adriamycin, belongs to the general group of drugs known as anthracyclines. It has FDA approval for use in treating cancer. Doxorubicin disrupts the growth of cancer cells, which are then destroyed.
Leiomyosarcoma response to doxorubicin [Adriamycin] including stable disease, is probably less than 50%. The median length of the remission or stability often being measured in a handful of months. Combinations of chemotherapy agents usually did not perform any better in terms of survival time than the individual agents themselves used separately.

Doxorubicin [Adriamycin] is exceedingly toxic and it is especially cardiotoxic. Because of the damage it does to cardiac muscle tissue, there is a lifetime personal limit of doxorubicin. Patients who are treated with doxorubicin [Adriamycin] need to have a MUGA scan or ultrasound ejection fraction done before treatment is started, and should be followed up with MUGA scans, or ejection fractions, to monitor for cardiac toxicity.

Doxorubicin [Adriamycin] also damages bone marrow cells, and Neupogen or Procrit may be necessary. Blood counts will be done before each dose is given. Doxorubicin can cause a decrease in the white blood cell count, especially 10-14 days after the drug is given. This can increase the risk of getting an infection. Report fevers of 100.5 F or higher, or signs of infection such as pain on passing urine, cough, and bringing up sputum to the doctor immediately. Doxorubicin can cause a decrease in the platelet count. This can increase the risk of bleeding. DO NOT take any aspirin or aspirin-containing medicines. Report unusual bruising, or bleeding such as nosebleeds, bleeding of gums when brushing teeth, or black, tarry stools.

Doxorubicin can cause radiation recall, which means it can "recall" damage from prior radiation therapy. Let your doctor or nurse know if skin gets red in areas where radiation treatment was given previously.

Doxorubicin can cause severe nausea and vomiting. If this side effect occurs, medication to control it is available.

Doxorubicin is given intravenously. If the drug accidentally leaks out of the vein where it is given, it WILL damage the tissue and cause scarring and pain. Tell the nurse right away if there is redness, pain, or swelling at the place of injection.

Neuropathy [nerve pain or tingling] might be helped with extra vitamin B6, or other B Vitamins. Other agents are sometimes used. Do ask your doctor.

A rash might come from tight fitting clothes, collars, shoes, underwear [women should not wear bras]. Do not use cortisone cream or Benadryl for the rash, but Nivea or Eucerin is recommended. ALWAYS check with your doctor.

Getting a wig before starting treatment may make it easier to deal with hair loss. Talk to the nurse or doctor about this. If insurance does not cover it, there may be other resources available to help. Hair loss is temporary, and hair will grow back after treatment. There is sometimes considerable pain with the hair loss, as the hair is lost. Note: After hair loss your head will be cold.


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

a. If you are pregnant, breastfeeding 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 without checking with your doctor.

b. 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.

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

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

While you are being treated with doxorubicin, and after you stop treatment, do not have any immunizations (vaccinations) without your doctor's okay. Try to avoid contact with people who have recently taken the oral polio vaccine. Check with your doctor about this.

Side Effects:

Bone Marrow [Decreased white blood cell count with increased risk of infection. Decreased platelet count with increased risk of bleeding. Decreased red blood cell count with increased fatigue.] Milder opportunistic infections such as thrush, vaginal candidiasis, and fungal infections of the nails are common.

Digestive System. [Loss of appetite. Sores in mouth or on lips. Nausea. Vomiting.]

Fatigue.

Skin/Hair/Nails
[Darkening of nail beds and skin creases of hands. Hair loss, occasionally with considerable pain until it all falls out. Radiation recall skin changes]

Heart [Temporary changes in electrocardiogram (EKG). Irregular heartbeat. Permanent Heart damage with congestive heart failure.]

Reproductive [Fetal abnormalities if taken while pregnant or if becoming pregnant while on this drug]


Letter from a previous User:

1) Leakage at the point of infusion MUST be avoided. Even excessive local tingling should be regarded as suspicious. After one dodgy infusion my wife's arm was sore for 2 months - only 1 out of 6 though.

2) Try very hard to alter the site of infusion (e.g. left arm, right arm). You need to allow the veins the maximum time to recover. Personally I think it should be given as high up the arm as possible i.e. in the largest vein. The procedure here is to use one of the small veins of the hand for all chemo. Unfortunately, my wife has very bad veins so its very difficult to find new ones - we should have pushed for a port. [There are complications with ports, too. Ed.]

3) I haven't heard of anyone in the UK being offered MUGA (admittedly limited experience), but unless you really had a massive tumor reduction after 6 doses, then I personally wouldn't consider more.

4) The figures I found (can't remember where) reported a very low level of heart problems (less than 1% from memory) with 6 doses, rising to 20% (again from memory) with 10.

5) This is a very toxic drug - very hard on the system, hits WBC levels very hard and also makes you very nauseated. Zofran helps this. My view - it's worth trying - you might be lucky - but unless you have a good reduction after 4 doses, try something else. Jim.


Another Letter from a previous AIM user [AIM is doxorubicin, ifosfamide, mesna]:

In answer to your question about 'What difference would having read your research made with my taking AIM?'
I took AIM after my second tumor was removed and there were no metastases. I'm not sure that was an informed and wise decision given LMS tumor resistance to chemo and the lasting damage to the body from chemo. I had high dose AIM. I knew about tumor resistance, but not about the permanent damage to the body.
General Information on Doxil
DOXIL

Doxil is a different form of doxorubicin, the surface area is protected by liposomes. Conventional doxorubicin is significantly bound to tissue and plasma proteins whereas the liposomal product is confined mostly to the vascular fluid and does not bind to plasma proteins. Doxil is supposed to penetrate the tumor better, and be less amenable to metabolic degradation.
It seems that Adriamycin is first line treatment IF your body is healthy enough to try it, and Doxil is considered for clinical trials, and for those who have significant heart disease or who wish a better side effect profile.

This the difference in the dosing regimes that the PDR recommends:
Adriamycin: 60-75 mg/m2 as a single injection every 21 days. Alternatively, 30 mg/m2 for 3 successive days q 4 weeks, or 20 mg/m2 weekly. Do not exceed a total dose of 550 mg/m2 This is a lifetime dose and that is another reason someone might receive Doxil.

Doxil: 20 mg/m2 over 30 min once every 3 weeks, as long as the client responds satisfactorily and tolerates the drug. Each cancer will have a different recommended dose so this is ONLY a recommendation. Usually in sarcomas you will see VERY HIGH dose therapy of both. The Marsden 2001 study that showed equivalence with Adriamycin had a Doxil dosage of 50 mg/m2 every 4 weeks.

There is a big difference in the incidence of side effects between the two medicines. For most people the Doxil side effects are less. You should be careful about the initial choice that is made for you, especially if you are being treated in a more rural area. Accidental substitution of Doxil for doxorubicin HCl has resulted in severe side effects. Do not substitute. The use of Doxil should be limited to physicians experienced in the use of cancer chemotherapeutic agents.

In clinical trials, the most common side effects reported with Doxil therapy included reduced red blood cell count (anemia), reduced white blood cell count (neutropenia), nausea, hand-foot syndrome, soreness of the mouth (stomatitis), weakness, vomiting, rash, mild hair loss, constipation, appetite loss, diarrhea, and tiredness. Some patients experienced infusion-related reactions and skin reactions. Hand-foot syndrome, also known as Palmar-plantar erthrodysesthesia (PPE), is characterized by symptoms of swelling, pain, redness and, for some patients, peeling of the skin on the hands and feet; in 17 percent of patients, these symptoms were moderate to severe.
Some severe heart-related side effects have been reported, and there is the possibility of severe bone marrow suppression. These are serious, potentially PERMANENT damages. Dosage should be reduced in patients with impaired liver function.

Experience with Doxil at high cumulative doses is too limited to have established its effects on the myocardium. Therefore, it should be assumed that Doxil will have myocardial toxicity similar to conventional formulations of doxorubicin HCl. Doxil should be administered to patients with a history of cardiovascular disease only when the benefit outweighs the risk.
Clinical Trial Results for Each

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 link, 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 "Doxorubicin 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.


Doxorubicin - Adriamycin Clinical Trials
Search Pubmed for LMS and doxorubicin clinical trials

Search Pubmed for sarcoma and doxorubicin clinical trials


Liposomal Doxorubicin - Doxil Clinical Trials
Search Pubmed for LMS and Doxil clinical trials

Search Pubmed for sarcoma and Doxil clinical trials


Epirubicin - Epiadriamycin Clinical Trials
Search Pubmed for LMS and Epirubicin clinical trials

Search Pubmed for sarcoma and Epirubicin clinical trials


ASCO Searches
You will have to go to the site and search year by year with keywords of the chemotherapy agent AND sarcoma.

ASCO abstracts search page



compiled by doctordee
update October 2003


The information on this site is not a substitute for professional medical advice. You should not use this information to diagnose or treat a health problem or disease without consulting with your doctor. Please consult your doctor with any questions or concerns you may have regarding your condition. Copyright 2001-2010 LMSWEBSITE