Doxorubicin(Myocet) 50mg powder, dispersion and solvent for concentrate for dispersion for infusion(三)
In a phase III study in combination with cyclophosphamide (CPA) comparing Myocet (60 mg/m2) + CPA (600 mg/m2) versus doxorubicin (60 mg/m2) + CPA (600 mg/m2), 6% versus 21% of patients, respectively, developed a significant decrease in left ventricular ejection fraction (LVEF). In a phase III study comparing single-agent Myocet (75 mg/m2) versus single-agent doxorubicin (75 mg/m2), 12% versus 27% of patients, respectively developed a significant decrease in LVEF. The corresponding figures for congestive heart failure (CHF), which was less accurately assessed, were 0% for Myocet + CPA versus 3% for doxorubicin + CPA, and 2% for Myocet versus 8% for doxorubicin. The median lifetime cumulative dose of Myocet in combination with CPA to a cardiac event was > 1260 mg/m2, compared to 480 mg/m2 for doxorubicin combination with CPA.
There is no experience with Myocet in patients with a history of cardiovascular disease, e.g. myocardial infarction within 6 months prior to treatment. Thus, caution should be exercised in patients with impaired cardiac function. The cardiac function of the patients treated concomitantly with Myocet and trastuzumab must be appropriately monitored as described below.
The total dose of Myocet should also take into account any previous, or concomitant, therapy with other cardiotoxic compounds, including anthracyclines and anthraquinones.
Before initiation of Myocet therapy a measurement of left ventricular ejection fraction (LVEF) is routinely recommended, either by Multiple Gated Arteriography (MUGA) or by echocardiography. These methods should also be applied routinely during Myocet treatment. The eva luation of left ventricular function is considered mandatory before each additional administration of Myocet once a patient exceeds a lifetime cumulative anthracycline dose of 550 mg/m2 or whenever cardiomyopathy is suspected. If LVEF has decreased substantially from baseline e.g. by > 20 points to a final value > 50% or by > 10 points to a final value of < 50%, the benefit of continued therapy must be carefully eva luated against the risk of producing irreversible cardiac damage. However, the most definitive test for anthracycline myocardial injury, i.e., endomyocardial biopsy, should be considered.
All patients receiving Myocet should also routinely undergo ECG monitoring. Transient ECG changes such as T-wave flattening, S-T segment depression and benign arrhythmias are not considered mandatory indications for the cessation of Myocet therapy. However, reduction of the QRS complex is considered more indicative of cardiac toxicity.
Congestive heart failure due to cardiomyopathy may occur suddenly, and may also be encountered after discontinuation of therapy.
Gastroinstestinal disorders
A meta-analysis showed a statistically significant lower rate of nausea/vomiting grade ≥ 3 (RR = 0.65, p=0.04) and diarrhoea grade ≥ 3(RR = 0.33, p=0.03) in patients treated with Myocet versus conventional doxorubicin.
Injection site reactions
Myocet should be considered an irritant and precautions should be taken to avoid extravasation. If extravasation occurs, the infusion should be immediately terminated. Ice may be applied to the affected area for approximately 30 minutes. Subsequently, the Myocet infusion should be restarted in a different vein than that in which the extravasation has occurred. Note that Myocet may be administered through a central or peripheral vein. In the clinical program, the |
