Doxorubicin


Article Author:
Kelly Johnson-Arbor
Hiren Patel


Article Editor:
Ramin Dubey


Editors In Chief:
Mohamed Alhajjaj
Richard Sue
Fatima Anjum


Managing Editors:
Avais Raja
Orawan Chaigasame
Khalid Alsayouri
Kyle Blair
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Abbey Smiley
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beenish Sohail
Hajira Basit
Phillip Hynes
Sandeep Sekhon


Updated:
11/4/2019 9:14:12 PM

Indications

Doxorubicin is an antibiotic derived from the Streptomyces peucetius bacterium. It has wide use as a chemotherapeutic agent since the 1960s. Doxorubicin is part of the anthracycline group of chemotherapeutic agents; other anthracyclines include daunorubicin, idarubicin, and epirubicin. Commonly, doxorubicin is an agent used in the treatment of solid tumors in adult and pediatric patients. Doxorubicin may be used to treat soft tissue and bone sarcomas as well as cancers of the breast, ovary, bladder, and thyroid. It is also used in the treatment of acute lymphoblastic leukemia, acute myeloblastic leukemia, Hodgkin lymphoma, and small cell lung cancer. The liposomal formulation of doxorubicin has FDA-approval for the treatment of ovarian cancer in patients who have failed platinum-based chemotherapy, AIDS-related Kaposi sarcoma, and multiple myeloma.[1][2][3][4]

Mechanism of Action

The primary mechanism of action of doxorubicin involves the drug’s ability to intercalate within DNA base pairs, causing breakage of DNA strands and inhibition of both DNA and RNA synthesis. Doxorubicin inhibits the enzyme topoisomerase II, causing DNA damage and induction of apoptosis. When combined with iron, doxorubicin also causes free radical-mediated oxidative damage to DNA, further limiting DNA synthesis. Iron chelators, such as dexrazoxane, may prevent the free radical formation by limiting the binding of doxorubicin with iron.

Administration

Doxorubicin is administered intravenously and is commonly given in 21-day intervals. The drug is easily recognizable in its liquid form due to its highly pigmented, reddish appearance. Doxorubicin is incompatible with heparin and fluorouracil and can cause precipitation if mixed with these drugs. While doxorubicin may be administered rapidly (over 15 to 20 minutes), slow administration of the liposomal formulation is recommended to reduce the risk of infusion reactions. Doxorubicin should be stored in a refrigerated area and re from light before administration. Doxorubicin exhibits rapid distribution into tissues and has an elimination half-life of up to 48 hours. Doxorubicin undergoes enzymatic reduction andquires protection undergoes elimination through biliary excretion.

Adverse Effects

Adverse reactions are common after doxorubicin administration and may include fatigue, alopecia, nausea and vomiting, and oral sores. Bone marrow suppression and an increased risk of secondary malignancy diagnoses may occur. Doxorubicin extravasation during intravenous administration can result in severe tissue ulceration and necrosis, which worsens over time. Doxorubicin is also associated with significant cardiac toxicity, which limits the long-term use of the drug. The mechanism of action of doxorubicin-induced cardiac toxicity differs from the drug’s antitumor mechanism. It involves increased oxidative stress, down-regulation of cardiac-specific genes, and induction of cardiac myocyte apoptosis by doxorubicin. The acute cardiac toxicity of doxorubicin occurs within days of the drug’s administration and occurs in approximately 11% of patients who receive the drug. Acute cardiac toxicity manifests as a reversible myopericarditis, left ventricular dysfunction, or arrhythmias. Doxorubicin-related arrhythmias occur in up to 26% of patients who receive the therapy and can include sinus tachycardia, premature atrial and ventricular contractions, and supraventricular tachycardia. Rarely, acute left ventricular dysfunction can occur after doxorubicin administration; this condition is reversible. Chronic, late cardiac toxicity may also occur after doxorubicin administration and is the most serious and potentially lethal adverse effect associated with doxorubicin therapy. The incidence of chronic doxorubicin cardiac toxicity is approximately 1.7%. Doxorubicin-induced irreversible cardiomyopathy occurs within a few months of the end of treatment but has also been reported to occur up to twenty years after treatment termination. Congestive heart failure may also occur. Risk factors for doxorubicin-induced congestive heart failure include a higher cumulative drug dose, extremes of age, combination chemotherapy with other cardiotoxic drugs, pre-existing left ventricular dysfunction, hypertension, and previous radiation to the mediastinal region. When congestive heart failure develops after doxorubicin administration, the 1-year mortality rate is approximately 50%.[5][6][7]

Contraindications

Doxorubicin is frequently listed as a contraindication to hyperbaric oxygen therapy (HBO). Animal studies of the combined administration of HBO and doxorubicin have shown different results, leading to controversy as to whether HBO is indeed contraindicated in patients receiving the drug. HBO was studied in 1985 along with the use of antioxidants, as a potential nonsurgical remedy for skin necrosis due to doxorubicin extravasation. In this study, researchers fed groups of rats antioxidants (beta-carotene and/or butylated hydroxytoluene (BHT), a common food preservative and known free radical scavenger). Subsequently, the rats were anesthetized and injected intradermally with doxorubicin. Some rats were then exposed to HBO at 2.5 ATA after the doxorubicin injections. The rats that were fed BHT before doxorubicin injection exhibited improved wound healing. The group of rats that received HBO after doxorubicin injection experienced an 87% mortality rate, which the authors attributed to the formation of free radicals by both HBO and doxorubicin. While the results of this single study suggest that the concurrent administration of HBO and doxorubicin may be associated with increased mortality, subsequent studies have not demonstrated an increase in mortality or cardiac toxicity after administration of HBO and doxorubicin. The effects of HBO after remote doxorubicin administration are unknown. It may be safe to administer HBO after doxorubicin has been cleared from the body, in other words, after five to six elimination half-lives, or 12 days). Still, additional studies are necessary for further exploration of this topic.

Monitoring

Baseline (pre-treatment) and regular monitoring of cardiac function, through the use of echocardiography or multi-gated radionuclide angiography (MUGA scan), is recommended for patients who are undergoing treatment with doxorubicin. Patients who exhibit a decrease in left ventricular ejection fraction during doxorubicin treatment should have the drug discontinued. Endomyocardial biopsy may also be utilized to diagnose doxorubicin-induced cardiomyopathy; findings include loss of myofibrils and cytoplasm vacuolization. Unfortunately, there is no specific treatment available for patients diagnosed with doxorubicin-induced cardiomyopathy. Diuretics and beta-adrenergic blockers are a potential option, but these treatments do not improve overall patient prognosis. Cardiac transplantation has been successful in some patients with doxorubicin-induced cardiomyopathy. Since higher cumulative doxorubicin doses are a risk factor for the development of cardiomyopathy, dose limitation is advocated to reduce cardiotoxicity. Antioxidant drugs (including amlodipine and carvedilol) have been studied as potential preventive agents to reduce the incidence of doxorubicin-induced cardiotoxicity. Dexrazoxane, an iron chelator, may be co-administered with doxorubicin to reduce the cardiotoxicity of the drug. However, the administration of dexrazoxane may induce myelosuppression, which can be potentiated by doxorubicin, so its clinical efficacy remains in question.

Enhancing Healthcare Team Outcomes

Doxorubicin is a frequently used chemotherapeutic agent for the treatment of many solid tumors and requires the efforts of an interprofessional healthcare team to be effective. While the drug is effective, it does have one serious adverse effect. Healthcare workers, including the primary care provider and nurse practitioner who refer patients to the oncologist, need to perform a cardiac screen test on patients with risk factors for heart disease. The reason is that doxorubicin can cause irreversible cardiomyopathy what may occur at any time after treatment

Baseline (pre-treatment) and regular monitoring of cardiac function, through the use of echocardiography or multi-gated radionuclide angiography (MUGA scan), is recommended for patients who are undergoing treatment with doxorubicin. The prescribing clinician would do well to include an oncology board-certified pharmacist Patients who exhibit a decrease in left ventricular ejection fraction during doxorubicin treatment should have the drug discontinued. Oncology nurses can also be beneficial in verifying therapy effectiveness and watching for adverse events. Since higher cumulative doxorubicin doses are a risk factor for the development of cardiomyopathy, dose limitation is advocated to reduce cardiotoxicity.[1][8][9] These are a few examples of interprofessional collaboration to maximize therapeutic results. [Level V]


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Doxorubicin - Questions

Take a quiz of the questions on this article.

Take Quiz
A male with prostate cancer was treated with combination chemotherapy. Six months after completing his therapy, he presented to the emergency department with dyspnea and fatigue. Work up revealed that he has congestive heart failure. Which agent is most likely to cause this complication?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A patient develops congestive heart failure after starting a chemotherapy drug. Which agent is most likely to cause this complication?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 63-year-old man with a past medical history of essential hypertension and type 2 diabetes mellitus presents to the clinic for follow up. He has been receiving aggressive immunosuppressive therapy for the past two months to treat Hodgkin Lymphoma. Per patient history, he has developed orthopnea, fatigue, and lower extremity edema. His most recent diagnostic studies indicate he has a reduced ejection fraction. Which of the following derivative does the chemotherapeutic agent most likely used in this patient belong to?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A patient with a lymphoma is being treated with combination chemotherapy. After a month, the patient is found to have tachycardia and dyspnea on exertion. What is the most likely agent responsible?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following agents has cardiac toxicity as its limiting factor?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Patients receiving initial treatment with doxorubicin hydrochloride should be informed of which of the following?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following types of chemotherapy is not matched correctly with one of its side effects?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 62-year-old man with non-Hodgkin lymphoma comes to the physician because of a 2-week history of progressive shortness of breath and lower extremity edema. He received his third course of chemotherapy 5 weeks ago. Physical examination revealed S3 heart sounds, crackles bilaterally lower based lung fields, and 4+ lower extremity edema. Which of the following is the mechanism of action of the agent most likely responsible for this patient's clinical status?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which is a known side effect of doxorubicin?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which drug is cardiotoxic?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A patient is starting chemotherapy with doxorubicin. Which one of the following is a teaching point for this medication?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following chemotherapy agents can cause an irreversible, dose-related cardiomyopathy and has a lifetime dose maximum?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What is the description of the liposomal technology used with doxorubicin?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which adverse effect is associated with doxorubicin?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which one of the following conditions is a possible indication for doxorubicin?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A patient with acute lymphocytic leukemia is being treated with doxorubicin. Which of the following are possible adverse effects? Select all that apply.



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 57-year-old woman with a past medical history of essential hypertension and type 2 diabetes mellitus presents to the clinic for follow up. She has failed treatments with platinum-based chemotherapy for ovarian cancer. Treatment with a liposomal formulation of a FDA-approved antibiotic chemotherapeutic agent is considered. Which of the following tests is most appropriate to order before initiating treatment with the new medication?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 66-year-old woman with a past medical history of osteoarthritis and type 2 diabetes mellitus presents to the clinic for follow up. She has failed treatments with platinum-based chemotherapy for ovarian cancer. Which of the following best describes the mechanism of action of the next best medical therapy indicated for this patient?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 58-year-old man presents to the clinic with a recent diagnosis of AIDS-related Kaposi sarcoma. He complains of chronic fatigue, weakness, and weight loss for the last 6 months. A liposomal preparation of an anti-tumor chemotherapeutic agent is being considered. Which of the following agents would be best indicated to supplement along with medical therapy to prevent drug side-effects?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 67-year-old man is brought to the hospitala with headache, confusion, and cherry red skin. He was rescued out of a burning building. His wife states, he was recently diagnosed with multiple myeloma and started on disease-modifying therapy. After several weeks into starting medical therapy for multiple myeloma, the patient began to experience orthopnea, dyspnea upon exertion, and fatigues. Upon physical examination, the clinician appreciates an S3 heart sound, new systolic regurgitant murmur, and jugular venous distention, and diffuse first-degree burns. Laboratory and diagnostic studies include reduced ejection fraction, dilated ventricles, and a widened QRS complex. Which one of the following therapeutic options is most strongly contraindicated to use in this patient's clinical status?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Doxorubicin - References

References

Yu AF,Chan AT,Steingart RM, Cardiac Magnetic Resonance and Cardio-Oncology: Does T{sub}2{/sub} Signal the End of Anthracycline Cardiotoxicity? Journal of the American College of Cardiology. 2019 Feb 26;     [PubMed]
Marcq G,Jarry E,Ouzaid I,Hermieu JF,Henon F,Fantoni JC,Xylinas E, Contemporary best practice in the use of neoadjuvant chemotherapy in muscle-invasive bladder cancer. Therapeutic advances in urology. 2019 Jan-Dec;     [PubMed]
Tantari M,Barra F,Di Domenico S,Ferraioli D,Vellone VG,De Cian F,Ferrero S, Current state of the art and emerging pharmacotherapy for uterine leiomyosarcomas. Expert opinion on pharmacotherapy. 2019 Feb 6;     [PubMed]
Koleini N,Nickel BE,Edel AL,Fandrich RR,Ravandi A,Kardami E, Oxidized phospholipids in Doxorubicin-induced cardiotoxicity. Chemico-biological interactions. 2019 Jan 29;     [PubMed]
Oikonomou E,Anastasiou Μ,Siasos G,Androulakis E,Psyrri A,Toutouzas K,Tousoulis D, Cancer Therapeutics-Related Cardiovascular Complications. Mechanisms, Diagnosis and Treatment. Current pharmaceutical design. 2019 Jan 10;     [PubMed]
Luu AZ,Chowdhury B,Al-Omran M,Teoh H,Hess DA,Verma S, Role of Endothelium in Doxorubicin-Induced Cardiomyopathy. JACC. Basic to translational science. 2018 Dec;     [PubMed]
Pipicz M,Demján V,Sárközy M,Csont T, Effects of Cardiovascular Risk Factors on Cardiac STAT3. International journal of molecular sciences. 2018 Nov 12;     [PubMed]
Abdullah CS,Alam S,Aishwarya R,Miriyala S,Bhuiyan MAN,Panchatcharam M,Pattillo CB,Orr AW,Sadoshima J,Hill JA,Bhuiyan MS, Doxorubicin-induced cardiomyopathy associated with inhibition of autophagic degradation process and defects in mitochondrial respiration. Scientific reports. 2019 Feb 14;     [PubMed]
Skála M,Hanousková B,Skálová L,Matoušková P, MicroRNAs in the diagnosis and prevention of drug-induced cardiotoxicity. Archives of toxicology. 2019 Jan;     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Pulmonary. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Pulmonary, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Pulmonary, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Pulmonary. When it is time for the Pulmonary board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Pulmonary.