Cardiotoxicity The most dangerous side effect of<unk>  is dilated cardiomyopathy, leading to congestive heart failure. The rate of cardiomyopathy is dependent on its cumulative dose, with an incidence about 4% when the dose of<unk>  is 500–550 mg/m2, 18% when the dose is 551–600 mg/m2 and 36% when the dose exceeds 600 mg/m2. There are several ways in which<unk>  is believed to cause cardiomyopathy, including oxidative stress, downregulation of genes for contractile proteins, and p53-mediated apoptosis.<unk> -induced cardiomyopathy typically results in dilated cardiomyopathy, with all four cardiac chambers being enlarged. This results in both systolic and diastolic dysfunction. Eventually, heart failure can result, which carries a 50% mortality rate. There is no effective treatment against established cardiomyopathy caused by the<unk> ug as of 2010. The<unk> ug dexrazoxane may be used to decrease the risk of<unk> 's cardiotoxicity in certain cases. Other Another common and potentially fatal complication of<unk>  is typhlitis, an acute life-threatening inflammation of the bowel. Additionally, some people may develop PPE, characterized by skin eruptions on the palms of the hand or soles of the feet, swelling, pain, and erythema. Due to these side effects and its red color,<unk>  has earned the nickname "red devil" or "red death." Chemotherapy can cause reactivation of hepatitis B, and<unk> -containing regimens are no exception.<unk>  and several chemotherapeutic<unk> ugs (including cyclophosphamide) can cause a loss of skin pigmentation. Liposomal formulations There is a pegylated (polyethylene glycol coated) liposome-encapsulated form of<unk> , developed to treat Kaposi's sarcoma The polyethylene glycol coating results in preferential concentration of<unk>  in the skin. However, this also results in a side effect called palmar plantar erythrodysesthesia (PPE), more commonly known as hand-foot syndrome. Following<unk> inistration of this form of<unk> , small amounts of the<unk> ug can leak from capillaries in the palms of the hands and soles of the feet. The result of this leakage is redness, tenderness, and peeling of the skin that can be uncomfortable and even painful. In clinical testing at 50 mg/m2 dosing every 4 weeks, half of people developed hand-foot syndrome. The rate of this side effect limits the dose of this formulation that can be given as compared with plain<unk>  in the same treatment regimen, thereby limiting potential substitution. Substitution would be desirable because liposome-encapsulated<unk>  is less cardiotoxic than unencapsulated<unk> . This liposome-encapsulated form is also approved by the FDA for treatment of ovarian cancer and multiple myeloma. A non-pegylated liposomal<unk> , called Myocet, is approved in the European Union and in Canada for the treatment of metastatic breast cancer in combination with cyclophosphamide, but it has not been approved by the FDA for use in the United States. Unlike<unk> il, the Myocet liposome does not have a polyethylene glycol coating, and therefore does not result in the same rate of PPE. The minimization of this side effect may allow for one-for-one (1:1) substitution with<unk>  in the same treatment regimen, thereby improving safety with no loss of efficacy. Like<unk> il, the liposomal encapsulation of the<unk>  limits the cardiotoxicity. In theory, by limiting the cardiotoxicity of<unk>  through liposomal encapsulation, it can be used safely in concurrent combination with other cardiotoxic chemotherapy<unk> ugs, such as trastuzumab. There is an FDA black box warning that trastuzumab cannot be used in concurrent combination with<unk> , only in sequential combination. Though concurrent combination of trastuzumab and<unk>  in clinical studies found superior tumor response, the combination resulted in unacceptable cardiotoxicity, including risk of cardiac failure manifesting as congestive heart failure (CHF). Published phase II study results have shown that Myocet, trastuzumab, and paclitaxel can safely be used concurrently without the cardiac risk, as measured by reduction in LVEF function, while still achieving superior tumor response. This finding is the basis for the ongoing phase III trial for FDA approval.
Doxorubicin
Paclitaxel
Ifosfamide
Epirubicin
Vincristine
Mitoxantrone
Docetaxel
Bleomycin