Doxorubicin dosage

The main dose-limiting toxicity of all anthracyclines is myelosuppression, with neutropenia more commonly observed than thrombocytopenia. In some cases, mucositis is dose-limiting. Two forms of cardiotoxicity are observed. The acute form occurs within the first 2-3 days and presents as arrhythmias or conduction abnormalities, other electrocardiographic changes, pericarditis, and myocarditis. This form is usually transient and is asymptomatic in most cases. The chronic form results in a dose-dependent, dilated cardiomyopathy associated with heart failure. The chronic cardiac toxicity appears to result from increased production of free radicals within the myocardium. This effect is rarely seen at total doxorubicin dosages below 500-550 mg/m2. Use of lower weekly doses or continuous infusions of doxorubicin appear to reduce the incidence of cardiac toxicity. In addition, treatment with the iron-chelating agent dexrazoxane (ICRF-187) is currently approved to prevent or reduce anthracycline-induced cardiotoxicity in women with metastatic breast cancer who have received a total cumulative dose of doxorubicin of 300 mg/m2. All anthracyclines can produce "radiation recall reaction," with erythema and desquamation of the skin observed at sites of prior radiation therapy. 

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

Loehrer PJ, Elson P, Dreicer R, et al. Escalated dosages of methotrexate, vinblastine, doxorubicin, and cisplatin plus recombinant human granulocyte colony-stimulating factor in advanced urothelial carcinoma an Eastern Cooperative Oncology Group trial. J Clin Oncol 1994 12 483-488. 

DOXORUBICIN CICLOSPORIN High doses of cidosporin t AUC of doxorubicin by 48% and of a metabolite by 443%. Risk of severe myelosuppression and neurotoxicity Cidosporin inhibits P-gp and selectively inhibits cytochrome P450 isoenzymes, which results in L clearance of doxorubicin Advise patients to report symptoms such as sore throat, fever, bleeding and bruising (i.e. of myelosuppression) and confusion, headache, coma and seizures (i.e. of neurotoxicity). 1 dosage of doxorubicin is often necessaiy... 

When used concomitantly, other nephrotoxic drugs may potentiate the nephrotoxicity caused by streptozocin. Concomitant use with doxorubicin prolongs the elimination half-life of doxorubicin and requires a reduced dosage of doxorubicin. Concurrent use with phenytoin may decrease the effects of streptozocin on the pancreas. 

Despite their usefulness, both daunorubicin and doxorubicin have several acute and long-term side effects. The most severe of these is cumulative cardiotoxicity [14], since it limits the dosage that can be prescribed. In addition, the emergence of multi-drug resistance in cancer cells upon long-term treatment poses serious problems in the clinic. Therefore it is not surpris-... 

Etretinate. A man with T-cell lymphoma who had recently been given chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisolone) was anticoagulated with warfarin after developing a pulmonary embolism. About three weeks later, he started etretinate 40 mg daily and it was found necessary to increase his warfarin dosage from 7 to 10 mg daily. His liver function tests were normal. This patient had also recently started taking co-proxamol , (p.436), tolbutamide , (p.380) and cimeti-dine , (p.412) , but all of these have been reported to only rarely increase the effect of warfarin. 

A comparative study in patients given doxorubicin found that those also taking barbiturates had a plasma clearance that was 50% higher than those who were not (318 mL/minute eompared with 202 mL/minute). This olinieal study is in agreement with previous studies in mice A possible explanation is that the barbiturate inereases the metabolism of the doxoru-biein. It seems possible that the dosage of doxorubiein will need to be inoieased in barbiturate-treated patients to aehieve maximal therapeutie effeets. 

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