Doxorubicin is one of the most active chemotherapies against many types of sarcomas. Indeed, the first line treatment for Ewing’s sarcoma often consists of cycles of vincristine, doxorubicin, and cyclophosfamide alternated with cycles of etoposide and ifosfamide.
Doxorubicin (also known as adriamycin) is in a class of chemotherapy drugs known as anthracyclines. It acts mainly by sticking in between DNA base pairs and obstructing replication of the genetic material, thereby inhibiting tumor growth. It is an orange colored clear fluid, given intravenously (through a small piece of tubing inserted into the patient's vein), either in a peripheral (arm) vein or a central line using a Hickman catheter, Broviac catheter, or a port-a-cath. It can be given over a variety of time frames, from 15 minutes to 72 hours.
Because doxorubicin is a vesicant (meaning it can cause severe tissue damage if it leaks out of the vein), it is strongly recommended that it be given in a central line. If given in a peripheral vein using a temporary IV, it must be given carefully by trained oncology nurses. During infusion patients may experience nausea, and, rarely, heart arrhythmias. Doxorubicin has a moderate to high incidence of nausea and patients should be well pre-medicated with anti-nausea medications. It causes hair loss, reddish discoloration of urine, and darkening of the skin and nails.
Doxorubicin causes suppression of blood counts: low white blood cells make the immune system weak, low red blood cells (anemia) causes fatigue and short-windedness and can be treated with blood transfusions, and low platelets can increase bruising and bleeding and can be treated with transfusions. Doxorubicin also causes mucositis, which is inflammation and ulceration of the lining of the mouth, throat, and rectum. It can be severe enough to impact ability to eat, and predispose to rectal infections. Supportive care includes good mouth care (soft toothbrushes and special prescription mouthwashes), stool softeners to avoid rectal tears, and pain medications as needed. Several other medicines are being looked at to treat mucositis; some advocate the use of glutamine, an essential amino acid, available by prescription or at health food stores, to speed mucosal healing.
The most concerning toxicity is cardiotoxicity, or heart damage, usually in the form of congestive heart failure. This is a condition of weakening of the heart muscles, resulting in shortness of breath, swelling of feet and lower legs, fast or irregular heartbeat. The incidence increases with total doses of drug received; it is uncommon with less than 300 mg/m2 and most common in those who get more than 550 mg/m2. Most Ewing’s protocols give in the range of 375 mg/m2 total dose. This cardiotoxicity is monitored for by studies of the heart function such as an echocardiogram (a sonogram that pictures the heart while contracting) or a MUGA (a nuclear medicine scan that quantitates heart contractile strength). These studies should be done while on therapy and then at intervals off therapy. The cardiotoxicity usually occurs within 1-6 months of chemotherapy, but can occur late.
Ongoing studies are looking at very late effects; for example, "What happens when someone who got doxorubicin when they were age 10 gets coronary artery disease at age 55?" Young women who have received doxorubicin should remind their doctor to monitor them carefully during pregnancy, as pregnancy puts an extra strain on the heart. A drug called Dexrazoxane is available that appears to protect the heart from anthracycline toxicity. Because it is not proven that it does not also protect the tumor, it is not recommended that it be given unless the patient is receiving significantly more than 300 mg/m2, or on a clinical trial. Doxil is a formulation of doxorubicin that is released more slowly in the body and therefore has different side effects. It may be as effective as standard doxorubicin in the treatment of sarcoma. It has not been used as primary therapy for Ewing’s but might be considered in recurrent or metastatic cases.