Cardiotoxicity doxorubicin

Kruizinga, W., and Hillen, F. C. (1989b). A comparative study on antitumor effect, cardiotoxicity and nephrotoxicity of doxorubicin administered as bolus, continuous infusion or entrapped in liposomes in the Lou/M Wsl rat, Cancer Chemother. Pharmacol. 24, 341-348. 

Liposomal doxorubicin is an irritant, not a vesicant, and is dosed differently from doxorubicin, so clinicians need to be very careful when prescribing these two drugs. The pharmacokinetics of liposomal doxorubicin are best described by a two-compartment model, with a terminal half-life of 30 to 90 hours.20 Liposomal doxorubicin has shown significant activity in the treatment of breast and ovarian cancer, along with multiple myeloma and Kaposi s sarcoma. Side effects include mucositis, myelosuppression, alopecia, and palmar-plantar erythrodysesthesia. The liposomal doxorubicin may be less cardiotoxic than doxorubicin. 

Doxorubicin 3 hours cycles 1 2 and then infused over 1 hour thereafter repeat every 28 days mucositis, alopecia, flushing, shortness of breath, hypotension, headaches, cardiotoxicity, hand-foot syndrome dysfunction. 2. Do not give if total bilirubin is greater than 5 mg/dL. 

Trastuzumab-monitorfor cardiotoxicity increases with concur-rent Doxorubicin ... 

Doxorubicin—monitor cumulative dose for cardiac toxicity vesicant—avoid extravasation can give larger cumulative doses than standard because less cardiotoxic by continuous infusion use 50% for bilirubin 1.5-3.0 use 25% for bilirubin >3.0... 

Doxorubicin - anthracycline antitumor antibiotic - DNA intercalating agent -bone marrow suppression -nausea and vomiting -mucocutaneous effects (mucositis, stomatitis) -cardiotoxicity (550 mg/M2) -vesicant if extravasated -rash and hyperpigmentation -alopecia (universal)... 

Liposomal doxorubicin—bone marrow suppression significantly less stomatitis, exstravasation necrosis, and cardiotoxicity ... 

Trastuzumab (Herceptin) -humanized mouse monoclonal antibody directed against HER-2/new receptor -fevers, chills, nausea, vomiting, headache during administration -cardiotoxicity (the FDA has not approved concurrent use with doxorubicin)... 

I 12. The answer is b. (Hardman, pp 1264-1265J Dactinomycin s major toxicities include stomatitis, alopecia, and bone marrow depression. Bleomycin s toxicities include edema of the hands, alopecia, and stomatitis. Mitomycin causes marked bone marrow depression, renal toxicity, and interstitial pneumonitis. Plicamycin causes thrombocytopenia, leukopenia, liver toxicity, and hypocalcemia. The latter may be of use in the treatment of hypercalcemia. Doxorubicin causes cardiotoxicity, as well as alopecia and bone marrow depression. The cardiotoxicity has been linked to a lipid peroxidation within cardiac cells. 

Anthracyclines (daunorubicin, doxorubicin, idarubicin, and epirubicin) are anticancer drugs widely used to manage patients with acute leukemia or breast cancer.22-23 To maximize therapeutic efficacy and minimize the acute myelosuppression and cumulative dose-related cardiotoxicity of these agents, several analytical methods were developed to measure anthracyclines and their metabolites in biologic fluids,24 26... 

MTX elimination [148,149], Similar studies have demonstrated the role of genetic variations in the ABCC2 gene on doxorubicin-induced cardiotoxicity [150],... 

Doxorubicin is a chemotherapeutic onthrocycline antibiotic, which may cause cordiotoxicity through the free-radical mechanism. Cardiotoxicity limits the clinical usefulness as a result of which doxorubicin has a total cumulative dose of about 450 mg/m body surface area. Patients with pre-existing cardiac disease, elderly patients and patients who have received myocardial irradiation must be treated cautiously and cardiac monitoring may be required. 

Dexrazoxane (Zinecard) [Chelating Agent] Uses Prevent anthracycline-induced (eg, doxorubicin) cardiomyopathy Action Chelates heavy metals binds intracellular iron prevents anthracycline-induced free radicals Dose 10 1 ratio dexrazoxane doxorubicin 30 min prior to each dose, 5 1 ratio w/ CrCl <40 mL/min Caution [C, ] Contra Component sensitivity Disp Inj SE -1-BM (esp leukopenia), fever, Infxn, stomatitis, alopecia, NA /D Interactions t Length of muscle relaxation Wf succinylcholine EMS Given concurrent w/a chemo agent for treating CA to prevent cardiotox monitor for Infxn and reduced cardiac Fxn use caution w/ succinylcholine, reduced doses may be needed OD May cause extreme BM suppression symptomatic and supportive... 

C. The dose-limiting toxicity of bleomycin is pulmonary toxicity and that of cisplatin is renal. Doxorubicin produces cardiotoxicity hematoxicity is dose limiting for methotrexate. 

The anthracycline antibiotics, which include doxorubicin, daunorubicin, bleomycin, and mitomycin C, inhibit DNA and RNA synthesis. Doxorubicin also interfers with topoisomerase II (a DNA gyrase), the activity of which is markedly increased in proliferating cells. Structurally related to doxorubicin are epirubicin and mitozantrone. The cytotoxic antibiotics are used to treat leukaemias and lymphomas and also for solid tumours in the breast, lung, thyroid and ovary. Cardiotoxicity is the major dose-limiting factor, with arrhythmias and myocardial depression (Bacon and Nuzzo 1993). The chronic phase of cardiotoxicity is a dose-dependent cardiomyopathy that leads to congestive heart failure in 2-10% of patients. Myocardial injury is the result of oxygen free radical formation. Children are particularly sensitive to these cardiotoxic reactions and may require a heart transplant in their later years. Epirubicin is less cardiotoxic than doxorubicin. 

Doxorubicin Oxygen free radicals bind to DNA causing single- and double-strand DNA breaks inhibits topoisomerase II intercalates into DNA Breast cancer, Hodgkin s and non-Hodgkin s lymphoma, soft tissue sarcoma, ovarian cancer, non-small cell and small cell lung cancer, thyroid cancer, Wilms tumor, neuroblastoma Nausea, red urine (not hematuria) Cardiotoxicity (see text), alopecia, myelosuppression, stomatitis... 

Figure 7.47 The mechanism of cardiotoxicity of doxorubicin. The drug can acquire electrons from mitochondrial complex I. The quinone thus produced can donate the electron to oxygen, and the superoxide produced damages heart tissues and mtDNA. Abbreviation mtDNA, mitochondrial DNA.

Salvatore CA, Jacobson MA, Taylor HE, Linden J, Johnson RG (1993) Molecular cloning and characterization of the human A3 adenosine receptor. Proc Natl Acad Sci USA 90(21) 10365-10369 Shneyvays V, Mamedova L, Zinman T, Jacobson KA, Shainberg A (2001) Activation of A3 adenosine receptor protects against doxorubicin-induced cardiotoxicity. J Mol Cell Cardiol 33(6) 1249-1261... 

Oxidative stress reduces the rate of cell proliferation, and that occurring during chemotherapy may interfere with the cytotoxic effects of antineoplastic drugs, which depend on rapid proliferation of cancer cells for optimal activity. Antioxidants detoxify ROS and may enhance the anticancer effects of chemotherapy. For some supplements, activities beyond their antioxidant properties, such as inhibition of topoisomerase II or protein tyrosine kinases, may also contribute. ROS cause or contribute to certain side effects that are common to many anticancer drugs, such as gastrointestinal toxicity and muagenesis. ROS also contribute to side effects that occur only with individual agents, such as doxorubicin-induced cardiotoxicity, cisplatin-induced nephrotoxicity, and bleomycin-induced pulmonary fibrosis. Antioxidants can reduce or prevent many of these side effects, and for some supplements the protective effect results from activities other than their antioxidant properties. Certain side effects, however, such as alopecia and myelosuppression, are not prevented... 

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