Daunorubicin toxicity

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. 

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... 

Daunorubicin—monitor cumulative dose for possible cardiac toxicity vesicant-avoid extravasation... 

Anthracyclines are antitumor quinone containing antibiotics produced by different strains of Streptomyces. Some of them, such as adriamycin doxorubicin), and daunorubicin are broad spectrum antitumor compounds. They act by binding to DNA and interfering with DNA replication and gene transcription. Their limitations for clinical use are cardiac toxicity and drug resistance phenomena. Consequently, intense structure-activity relationship studies have been performed to improve the pharmacological profile as well as to enhance the affinity for DNA. In particular, a number of fluorinated anthracyclines have been prepared with introduction of fluorine atoms into D or A cycles, and into the aglycone side chain linked atC-14. ... 

Moreover, Fiorillo et al. [393] studied the effect of a combination of liposomal daunorubicin, etoposide, and carboplatin administered to seven children with recurrent malignant supratentorial brain tumors as a second-line therapy. Chemotherapy consisted of infusion of liposomal daunorubicin on days 1 and 2 and infusion of etoposide and carboplatin on day 1 whereas courses were repeated every 3M weeks. After a total of eight courses, five of seven children evaluated were alive 12-64 months after diagnosis and 8-29 months from the start of the second-line chemotherapy. Of the seven children, three showed complete response, two partial responses, one stable disease, and one progressive disease. The time to the best response was 3-10 months, while the median time to progression was 23 months. The toxicity observed was minimum. 

DAUNORUBICIN TRASTUZUMAB t risk of cardiac toxicity Possibly additive cardiac toxic effect Closely monitor cardiac function - clinically and electrocardiographically. 

Liposomal forms of doxorubicin (Caelyx, Myocet) and daunorubicin (DaunoXome) are in use. These drugs are licensed for the treatment of a wide range of tumors (Table 1). Much information regarding the anthracyclines has been previously published in major reviews and textbooks (1,2). With this in mind, their major toxic effects are outlined here, but concentrating in more detail on new findings, such as the interaction with trastuzumab. 

Acute overdose with pegylated liposomal doxorubicin worsens the toxic effects of mucositis, leukopenia, and thrombocj4openia. There have been no reports of overdose of liposomal daunorubicin, but the primary anticipated toxic effect would be myelosuppression. 

Daunorubicin is u.sed in the Irealmcnl of acute cytie and granulocytic leukemias.- - Toxic effects inclu . bone marrow depression, stomatitis, alopecia, and giMxr lestinal disturbances. At higher doses, cardiac loxicit) ir. develop. Severe and progressive congestive hean lajk may follow initial tachycardia and arrhythmias. 

The major toxicities of these four groups are bone marrow depression, nausea and vomiting, mucositis, and diarrhea. Daunorubicin, doxorubicin, epirubicin, idarubicin, and to a lesser extent, mitoxantrone, cause cardiac toxicity. Mitomycin and bleomycin cause... 

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