What is the lifetime or cumulative dose for Adriamycin?

• The recommended lifetime or cumulative dose for Adriamycin depends on a person’s risk for cardiotoxicity
• Lifetime cumulative doses of Adriamycin above 550 mg/m² (for 21-day cycles) are associated with an increased risk of cardiomyopathy
• In people at high risk of cardiotoxicity, the maximum lifetime cumulative dose of doxorubicin should not exceed 400 mg/m².

Adriamycin (doxorubicin) is a cancer medication that has been successfully used in the management of several different cancers such as acute lymphoblastic leukemia, acute myeloblastic leukemia, Wilm’s tumor, breast and ovarian carcinomas, and many other cancers.

It belongs to a class of medicines called anthracycline antibiotics. Adriamycin cannot be given to people who have already had previous treatment with the maximum cumulative doses of either doxorubicin, daunorubicin, idarubicin, or other anthracyclines or anthracenediones.

A lifetime or cumulative dose refers to the total amount of a drug (or radiation treatment) that has been given to a patient over time, or over their lifetime.

Certain medications, such as Adriamycin, have a maximum cumulative dose that may be given to each patient. The dose is limited to reduce the risk of toxic side effects, such as heart toxicity (cardiotoxicity).

Cardiotoxicity can be severe with Adriamycin treatment and may develop late during therapy, or within two to three months after the treatment has ended. Symptoms include signs or symptoms of heart failure, including a reduced ability of the left side of the heart to pump (called LVEF or left ventricular ejection fraction), a fast heartbeat, shortness of breath, fluid on the lungs, as well as other related symptoms.

The probability of developing heart problems (impaired myocardial function) increases the higher the cumulative dose of Adriamycin that has been given, for example, the probability is:

• 1-2% for a total cumulative dose of 300 mg/m² Adriamycin
• 3-5% for a total cumulative dose of 400 mg/m² Adriamycin
• 5-8% for a total cumulative dose of 450 mg/m² Adriamycin
• 6-20% for a total cumulative dose of 500 mg/m² Adriamycin.

The probability of developing congestive heart failure has been reported as:

• 1.5% for a cumulative dose of 300 mg/m² Adriamycin
• 3-4.9% for a cumulative dose of 400-430 mg/m² Adriamycin
• 7-7.7% for a cumulative dose of 450-475 mg/m² Adriamycin
• 20.5-21% for a cumulative dose of 500-728 mg/m² Adriamycin.

The risk of developing heart failure rapidly increases with increasing cumulative doses in excess of 400 mg/m² and when Adriamycin is used with other chemotherapy agents, such as cyclophosphamide, fluorouracil, or vincristine.

Cardiotoxicity may also occur at lower doses in seniors, people exposed to Adriamycin at a young age, concomitant use of other cardiotoxic drugs, calcium channel blockers, pre-existing heart disease, or prior radiation therapy to the heart. People prescribed the monoclonal antibody trastuzumab have a much higher risk of cardiotoxicity with Adriamycin at lower cumulative doses.

The package insert for Adriamycin states that lifetime cumulative doses above 550 mg/m2 (21-day cycles) are associated with an increased risk of cardiomyopathy.

In people at higher risk of cardiotoxicity, the maximum cumulative dose of doxorubicin should be limited to less than 400 mg/m².

In certain cases, people who have received total cumulative doses of 450 mg/m² may be considered for further therapy up to a total cumulative dose of 700 mg/m² provided they undergo cardiac assessment and are deemed to be suitable to continue treatment.

Dexrazoxane may be used for cardioprotection in patients with advanced or metastatic cancer who are at risk of developing cardiotoxicity when receiving Adriamycin.

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