Nursing Pharmacology Chapter 33-34:  Anticancer Drugs

• Natural Products: 

  • Topoisomerase Inhibitors Type II: Daunorubicin (Cerubidine)

    • Overview:

      • Historically, doxorubicin was the initial drug in the anthracycline class isolated.³ 

        • A prominent source of this agent and doxorubicin is Streptomyces peucetius (variation caesius).

          • Streptomyces peucetius variation caesius Microbial Culture Collection of Antibiotic Producers Ukraine http://lv-microbcollect.lviv.ua/en/strain_card/id/137/

        • Daunorubicin is often a component of the chemotherapy induction phase protocol for treating acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL).⁸ 

          • For AML, daunorubicin may be employed in combination with ara-C (cytarabine).¹  

            • Liposomal Daunorubicin & Cyarabine for AML⁹

              Attribution: Erba H et al.  Liposomal Daunorubicin & Cytarabine for AML https://www.youtube.com/watch?v=vOQZEQ_F0lc (1/2019) OncLive TV Youtube Channel:  https://www.youtube.com/channel/UC3aRpa3CR_w4JrxYv_r_pDg

      • Differing from doxorubicin, daunorubicin exhibits limited effectiveness in treating solid tumors.³

    • Absorption, Distribution, Biotransformation, Excretion:⁸ 

      • Daunorubicin, following IV infusion, exhibits rapid plasma clearance (principal half-life: 40 minutes).⁸

      • Doxorubicin exhibits hepatic metabolism and depends on the kidneys for drug elimination.

        • In patients with hepatic and renal dysfunction, daunorubicin doses would be typically reduced.

          • The criteria for dose reduction depends on either serum creatinine or bilirubin levels.

            • For a 50% dose reduction, for example, serum creatinine or bilirubin would be > 3 mg/dL.

            • A dose reduction by 25% may be recommended for bilirubin concentrations in the range of about 1.2 to 3.0 milligrams/dL.

        • The parent compound (daunorubicin) is extensively metabolized with prominent glucuronide forms found in the bile (phase II metabolism).

          • An alcohol metabolite is prominently noted following bolus doxorubicin administration and exhibits an extended half-life compared to the parent compound.

          • By contrast to doxorubicin, daunorubicin metabolism is an important characteristic of plasma pharmacology.⁸

      • High-Dose Anthracycline Terapy in AML¹⁰

        Attribution: Erba H et al.  High-Dose Anthracycline Therapy in AML https://www.youtube.com/watch?v=-pz3zWaRs4g (1/2019) OncLiveTV Youtube Channel:  https://www.youtube.com/channel/UC3aRpa3CR_w4JrxYv_r_pDg

     

    • Clinical Uses:

      • Daunorubicin is mainly used in treating acute leukemias, acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL).⁷ 

        • In the pediatric setting, acute lymphoblastic leukemia may be treated using daunorubicin (IV route of administration) in combination treatment with prednisone and vincristine.⁷

    • Adverse Effects/Side Effects:

      • Daunorubicin toxicity profiles are generally similar to that described earlier for doxorubicin.

      • These toxicities include:

        • Myelosuppression

        • Cardiac toxicity

        • Nausea

        • Vomiting

        • Alopecia

      • Daunorubicin is a notable vesicant.

         

        • "Full thickness skin necrosis presenting 48h following chemotherapy extravasation."¹⁰

          Attribution: (Ioannis Goutos) "Full thickness skin necrosis presenting 48h following chemotherapy extravasation."9 Goutos I CogswellLK Giel H Extravasation Injuries: a review.  The Journal of Hand Surgery [European Volume] 2014, Vol 38E(8) 808-818. https://www.researchgate.net/publication/259629745_Extravasation_injuries_A_review