Doxorubicin toxicity

CALCIUM CHANNEL BLOCKERS DOXORUBICIN t serum concentrations and efficacy of doxorubicin when co-administered with verapamil, nicardipine and possibly diltiazem and nifedipine however, no cases of doxorubicin toxicity have been reported Uncertain however, verapamil is known to inhibit intestinal P-gp, which may t the bioavailability of doxorubicin Watch for symptoms/signs of toxicity (tachycardia, heart failure and hand-foot syndrome)... 

Mostafa MG, Mima T, Ohnishi ST, et al. S-allylcysteine ameliorates doxorubicin toxicity in the heart and liver in mice. Planta Med 2000 66 148-151. 

Also the renal 3D models, which have been described recently, have been tested with <10 compounds and their predictivity is unclear. One of these renal 3D models is based on hydrogel-embedded PT isolated from murine kidneys (Astashkina et al., 2012a). Thus, two of the main potential advantages of in vitro models do not apply here, which are (1) use of human cells and (2) avoidance of animal experiments. The four compounds tested with this model included doxorubicin, which gave in addition to cisplatin the most consistent positive resnlts (cytokine release was measured as endpoint). However, in humans doxorubicin toxicity usually does not affect the PT. Doxorubicin has substantial hepato- and cardiotoxicity, but only ntinor toxic effects on the kidney, which are mainly limited to the glomerulus (Tacar et al., 2013). 

Zordoky BNM., Anwar-Mohamed A, Aboutabi ME, El-Kadi AO (2011) Acute doxorubicin toxicity differentially alters cytochrome P450 expression and arachidonic acid metabolism in rat kidney and liver. Drug Metab Dispos 39 1440-1450... 

Karimi et al. [230] Doxorubicin Cardiotoxicity Mice doxorubicin toxicity(15 mg/kg i.p) tomato extract (1.2 and 2.4 g/kg, i.p.) and lycopene (1.7 and 3.5 mg/kg, i.p.) Lycopene supplementation Prevented the rise in serum creatine kinase-MB Ameliorated cardiac cell injury... 

Because of its clinical importance and the expected benefits of the drug in liposomal form for cancer treatment, all three American "liposome enterprises" (i.e.. Liposome Technology Inc., Erbamont, LyphoMed/Vestar joint ventures, and the Liposome Company, Inc.) are developing a formulation of liposomal doxorubicin. Clinical studies already show promising results as far as the acute toxicity is concerned (less vomiting, nausea, and hair loss) (Gabizon et al., 1989 Treat et al., 1989),... 

This royal-blue-colored drug is an anthracenedione that inhibits DNA topoisomerase II. The pharmacokinetics of mitoxantrone may best be described by a three-compartment model, with an a half-life of 3 to 10 minutes, a 3 half life of 0.3 to 3 hours, and a median terminal half-life of 12 days. Biliary elimination appears to be the primary route of elimination, with less than 10% of the drug eliminated by the kidney.23 Mitoxantrone has shown clinical activity in the treatment of acute leukemias, breast and prostate cancer, and non-Hodgkin s lymphomas. Myelosuppression, mucositis, nausea and vomiting, and cardiac toxicity are side effects of this drug. The total cumulative dose limit is 160 mg/m2 for patients who have not received prior anthracycline or mediastinal radiation. Patients who have received prior doxorubicin or daunorubicin therapy should not receive a cumulative dose greater than 120 mg/m2 of mitoxantrone. Patients should be counseled that their urine will turn a blue-green color. 

In an attempt to reduce relapse rate and late toxicity, combined-modality therapy using lower doses of radiation and an abbreviated course of chemotherapy has been evaluated.16 The goal of decreased relapse rate has been achieved, but no overall survival benefit has been documented. A limitation of this approach is exposing patients to the additive toxicities of chemotherapy. Trials that have investigated this approach typically have incorporated between two and four cycles of a standard regimen for HL, such as ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) with involved-field radiation. At present, combined-modality therapy is considered to be a standard of care for stage I/II HL. 

For doxorubicin-containing regimens, total the cumulative dosage received by the patient to monitor for cardiac toxicity. 

Doxorubicin (Adriamycin) Myelosuppression, alopecia, cumulative dose-limiting toxicity, myocardium damage Given in combination with vincristine and dexamethasone (VAD)... 

The DNA forms stable complexes with doxorubicin (Adriamycin, ADR) and daunorubicin (DNR). Doxorubicin and DNR, although structurally similar, show distinctly different properties ADR is more toxic and active than DNR in the treatment of various human solid tumors the apparent binding affinity of ADR to DNA is about 1.8 times higher than that of DNR to DNA. Trouet et al. [229] found the ADR-DNA complex to be more active than ADR, DNR, or DNR-DNA in subcutaneously inoculated leukemic mice, whereas the DNR-DNA complex showed the highest... 

Doxorubicin—monitor cumulative dose for cardiac toxicity (not to exceed 550 mg/M2 or 450 mg/M2 with prior chest radiotherapy) vesicant—avoid extravasation use 50% for bilirubin 1.5-3.0 use 25% for bilirubin > 3.0... 

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