Neutropenia anthracycline

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. 

In Phase I trials in the UK, HPMA copolymer doxombicin (PKl) given once every three weeks, had significantly reduced toxicity when compared to free doxombicin. The maximum tolerated dose, toxicity profile, and pharmacokinetics of PKl as an i.v. infusion every 3 weeks to patients with refractory or resistant cancers was determined. In the most recent report, 100 cycles were administered (range, 20-320 mg/m [free dmg equivalent]) to 36 patients (20 males and 16 females) with a mean age of 58.3 years (age range, 34-72 years). The maximum tolerated dose was 320 mg/m, and the dose-limiting toxicities were febrile neutropenia and mucositis. This maximum tolerated dose was a 4-5 fold increase over the usual clinical doses (60-80 mg/m ). No congestive cardiac failure was seen despite individual cumulative doses up to 1680 mg/m. Other anthracycline-like toxicities were attenuated. Pharmacokinefically, PKl had a distribution t(l/2) of 1.8 h and... 

Chan A, Chen C, Chiang J, Tan SH, Ng R. Incidence of febrile neutropenia among early-stage breast cancer patients receiving anthracycline-based chemotherapy. Supportive Care Cancer 2012 20(7) 1525-32. 

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