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What are the long-term side effects of Adriamycin?

Medically reviewed by Carmen Fookes, BPharm. Last updated on April 20, 2020.

Official Answer

by Drugs.com

The most common long-term side effects associated with Adriamycin include:

  • Cardiotoxicity
  • Secondary cancers
  • Amenorrhea in women older than 40
  • Gastrointestinal problems
  • Neurological problems.

Adriamycin (doxorubicin) is a cancer medication that has been used successfully 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.

The most common long-term side effects associated with Adriamycin include:

  • Cardiotoxicity
  • Secondary cancers
  • Amerohhea in women older than 40
  • Gastrointestinal problems
  • Neurological problems.

Cardiotoxicity

Cardiotoxicity is one of the most common potential long-term side effects of Adriamycin. Cardiotoxicity means permanent damage to the muscles of the heart or the functioning of the heart.

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 cardiotoxicity 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 above 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. 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.

Secondary cancers

Many cancer treatments and radiation therapy are associated with an increased incidence of secondary cancers. These are cancers that occur years after the primary cancer has been treated, and may be related to the treatment used, rather than the primary cancer.

Adriamycin has been associated with an increased incidence of acute myelogenous leukemia and myelodysplastic syndrome. Leukemia may affect 2 to 12% of people who have been treated with Adriamycin and more commonly develops within one to three years of treatment. It is primarily associated with translocation of the MLL gene at chromosome band 11q23. It is more common in younger patients but it is unknown which patients are more at risk, although concurrent use of alkylating agents (such as cyclophosphamide, cisplatin, and chlorambucil) or radiation therapy increases this risk.

Menstrual changes

96% of women aged 40 to 49 prescribed Adriamycin developed amenorrhea (a lack of menstrual bleeding).

This was permanent for most women over 40. In those under 30, none experienced menstrual abnormalities, and for those aged 30 to 40 with amenorrhea, 50% had a return to normal of their periods once treatment finished.

Gastrointestinal

Long-term gastrointestinal side effects that have been reported with Adriamycin include:

  • Gastric ulcers or erosions
  • Hyperpigmentation of the tongue or oral mucosa (rare)
  • Ulceration and necrosis of the colon, especially the cecum (rare).

Neurological

Adriamycin has been associated with several long-term neurological side effects, such as:

  • Peripheral neuropathy: This is damage to the nerves that carry messages from the brain and spinal cord to the rest of the body. Symptoms may include cold hands and feet, poor limb circulation, pins and needles, numbness, an increased risk of infections and injury
  • Muscle weakness
  • Cognitive changes: Often described as “chemo fog”. These may cause difficulties with multitasking, concentrating, or headaches. In most people these are temporary; however, they may persist in some people.
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