Doxorubicin is an anthracycline class medication used in the management and treatment of various types of malignancies and tumors.
Non-FDA approved indications include:
Doxorubicin is one of the cytotoxic, anthracycline agents derived from Streptomyces spp. The anthracycline class of agents has similar mechanisms of action and work by intercalating between the DNA base pairs causing uncoiling of the DNA helical structure. This action causes inhibition of DNA synthesis and affects the activity of DNA topoisomerase II. Anthracyclines can also form free radicals which can target and damage rapidly growing cells.
Doxorubicin is a major substrate of cytochrome P450, CYP3A4, CYP2D6, and P-glycoprotein (Pgp). There have been several clinically significant interactions reported with other inhibitors of CYP3A4, CYP2D6, and/or Pgp that can increase doxorubicin concentration resulting in more or worsening side effects and toxicity at lower dosages.
Doxorubicin is available as a powder for injection or as a liquid solution [2 mg/mL] administered intravenously (IV) via a central line as a continuous infusion.
Adult dosing: 60 to 75 mg/m^2 intravenously (IV) every 21 days OR
Due to the side effect profile and toxicity of doxorubicin, patients are only allowed a lifetime dose of 550 mg/m^2. They are required to have close follow-up and monitoring of blood counts, liver function, and heart function studies.
Due to the cardiotoxic profile of doxorubicin, baseline left ventricular ejection fraction (LVEF) should be assessed and monitored routinely using an echocardiogram. An LVEF drop of greater than 10% from baseline is considered indicative cardiotoxicity, and immediate intervention by physicians and the healthcare team is required. An alternative to echocardiogram monitoring is radionuclide ventriculography, such as multigated acquisition angiogram (MUGA) or equilibrium radionuclide angiogram (ERNA) scans, although less frequently used.
Obtain baseline complete blood counts (CBC), hepatic enzymes, and tests of hepatic function.
Doxorubicin has been a mainstay in treating various cancers for many years, and members of the health care team must be aware and up to date on the indications, interaction, adverse effects, and other pharmacodynamic and pharmacokinetic factors that can affect successful therapy implementation, and lead to improved patient outcomes.
Prescribing and monitoring doxorubicin requires an interprofessional team of healthcare professionals that includes a nurse, laboratory technologists, pharmacists, and physicians in different specialties, including a primary medical doctor (internal medicine), cardiologist, and hematologist/oncologist.
Proper monitoring for complications, in particular, cardiac and hepatic, is indicated as a retrospective study reported cardiotoxicity in 26%, and the 1-year mortality with doxorubicin-induced cardiotoxicity is as high as 50%. Research has also shown cardiotoxicity to be the leading cause of death in patients taking anthracyclines, as seen by several extensive randomized clinical retrospective studies. [Level 1]
Regularly monitor complete blood counts and metabolic panels to monitor for myelosuppression. The medical team should respond and assess significant changes to consider halting the drug when indicated. This monitoring function often falls to the clinical pharmacist, who will track the necessary lab work and inform the ordering clinician regarding situations that require alterations in the regimen. Nursing will be well versed in administration and monitoring for side effects, particularly extravasation, and inform the team of any concerns.
Team coordination is also necessary when considering using dexrazoxane to decrease the risk of cardiotoxicity.
This type of interprofessional paradigm leads to the best patient result for anti-infective care with doxorubicin. [Level 5]
|||Meyer M,Seetharam M, First-Line Therapy for Metastatic Soft Tissue Sarcoma. Current treatment options in oncology. 2019 Jan 24; [PubMed PMID: 30675651]|
|||Megías-Vericat JE,Martínez-Cuadrón D,Sanz MÁ,Poveda JL,Montesinos P, Daunorubicin and cytarabine for certain types of poor-prognosis acute myeloid leukemia: a systematic literature review. Expert review of clinical pharmacology. 2019 Mar; [PubMed PMID: 30672340]|
|||Cytotoxic Antibiotics 2012; [PubMed PMID: 31643644]|
|||McGowan JV,Chung R,Maulik A,Piotrowska I,Walker JM,Yellon DM, Anthracycline Chemotherapy and Cardiotoxicity. Cardiovascular drugs and therapy. 2017 Feb; [PubMed PMID: 28185035]|
|||Doxorubicin 2012; [PubMed PMID: 31643934]|
|||Franco YL,Vaidya TR,Ait-Oudhia S, Anticancer and cardio-protective effects of liposomal doxorubicin in the treatment of breast cancer. Breast cancer (Dove Medical Press). 2018; [PubMed PMID: 30237735]|
|||Fukuda A,Tahara K,Hane Y,Matsui T,Sasaoka S,Hatahira H,Motooka Y,Hasegawa S,Naganuma M,Abe J,Nakao S,Takeuchi H,Nakamura M, Comparison of the adverse event profiles of conventional and liposomal formulations of doxorubicin using the FDA adverse event reporting system. PloS one. 2017; [PubMed PMID: 28953936]|
|||Antineoplastic Agents 2012; [PubMed PMID: 31643354]|
|||Hanf A,Oelze M,Manea A,Li H,Münzel T,Daiber A, The anti-cancer drug doxorubicin induces substantial epigenetic changes in cultured cardiomyocytes. Chemico-biological interactions. 2019 Nov 1; [PubMed PMID: 31545955]|
|||Pituskin E,Haykowsky M,McNeely M,Mackey J,Chua N,Paterson I, Rationale and design of the multidisciplinary team IntervenTion in cArdio-oNcology study (TITAN). BMC cancer. 2016 Sep 15; [PubMed PMID: 27629548]|
|||Lu P, Monitoring cardiac function in patients receiving doxorubicin. Seminars in nuclear medicine. 2005 Jul; [PubMed PMID: 16098293]|
|||Thorn CF,Oshiro C,Marsh S,Hernandez-Boussard T,McLeod H,Klein TE,Altman RB, Doxorubicin pathways: pharmacodynamics and adverse effects. Pharmacogenetics and genomics. 2011 Jul; [PubMed PMID: 21048526]|
|||Pugazhendhi A,Edison TNJI,Velmurugan BK,Jacob JA,Karuppusamy I, Toxicity of Doxorubicin (Dox) to different experimental organ systems. Life sciences. 2018 May 1; [PubMed PMID: 29534993]|
|||Chatterjee K,Zhang J,Honbo N,Karliner JS, Doxorubicin cardiomyopathy. Cardiology. 2010; [PubMed PMID: 20016174]|
|||Kalay N,Basar E,Ozdogru I,Er O,Cetinkaya Y,Dogan A,Inanc T,Oguzhan A,Eryol NK,Topsakal R,Ergin A, Protective effects of carvedilol against anthracycline-induced cardiomyopathy. Journal of the American College of Cardiology. 2006 Dec 5 [PubMed PMID: 17161256]|
|||Kim IH,Lee JE,Youn HJ,Song BJ,Chae BJ, Cardioprotective Effect of Dexrazoxane in Patients with HER2-Positive Breast Cancer Who Receive Anthracycline Based Adjuvant Chemotherapy Followed by Trastuzumab. Journal of breast cancer. 2017 Mar [PubMed PMID: 28382098]|
|||Abdel-Qadir H,Ong G,Fazelzad R,Amir E,Lee DS,Thavendiranathan P,Tomlinson G, Interventions for preventing cardiomyopathy due to anthracyclines: a Bayesian network meta-analysis. Annals of oncology : official journal of the European Society for Medical Oncology. 2017 Mar 1 [PubMed PMID: 28028033]|
|||Swain SM,Whaley FS,Ewer MS, Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer. 2003 Jun 1; [PubMed PMID: 12767102]|
|||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. 2018; [PubMed PMID: 30636595]|