Esme is receiving three chemotherapy medications during her treatment. Here is more information about each one.

Doxorubicin is a drug used in cancer chemotherapy. It is an anthracycline antibiotic, closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA, with the most serious adverse effect being life-threatening heart damage. It is commonly used in the treatment of a wide range of cancers, including hematological malignancies, many types of carcinoma, and soft tissue sarcomas.

The drug is administered intravenously, as the hydrochloride salt. Doxorubicin is photosensitive, and containers are often covered by an aluminum bag or brown wax paper to prevent light from affecting it.

Side effects
The most dangerous side effect of doxorubicin is heart damage. When the cumulative dose of doxorubicin reaches 550 mg/m², the risks of developing cardiac side effects, including CHF, dilated cardiomyopathy, and death, dramatically increase. Doxorubicin cardiotoxicity is characterized by a dose-dependent decline in mitochondrial oxidative phosphorylation. Reactive oxygen species, generated by the interaction of doxorubicin with iron, can then damage the myocytes (heart cells), causing myofibrillar loss and cytoplasmic vacuolization.

Another common and potentially fatal complication of doxorubicin is Typhlitis, an acute life-threatening infection of the bowel.

Acute adverse effects of doxorubicin can include heart arrhythmias, nausea, and vomiting. It can also cause neutropenia (a decrease in white blood cells), as well as complete alopecia (hair loss). A more mild side effect is discoloration of the urine, which can turn bright red for up to 48 hours after dosing.

Additionally, some patients 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, doxorubicin has earned the nickname “red devil.”

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Cisplatin is a chemotherapy drug. It was the first member of a class of platinum-containing anti-cancer drugs, which now also includes carboplatin and oxaliplatin. These platinum complexes react in vivo, binding to and causing crosslinking of DNA, which ultimately triggers apoptosis (programmed cell death).

Cisplatin is administered intravenously as short-term infusion in normal saline for treatment of solid malignancies. It is used to treat various types of cancers, including sarcomas, some carcinomas (e.g. small cell lung cancer, and ovarian cancer), lymphomas, and germ cell tumors.

Side effects
Nephrotoxicity (kidney damage) is a major concern. The dose is reduced when the patient’s creatinine clearance (a measure of renal function) is reduced. Adequate hydration and diuresis is used to prevent renal damage. Nephrotoxicity is a dose-limiting side effect.

Neurotoxicity (nerve damage) can be anticipated by performing nerve conduction studies before and after treatment. Common neurological side effects of Cisplatin include visual perception and hearing disorder, which can occur soon after treatment begins.
Cisplatin is one of the most emetogenic chemotherapy agents, but this symptom is managed with prophylactic antiemetics (ondansetron, granisetron, etc.) in combination withcorticosteroids.
Ototoxicity (hearing loss): there is at present no effective treatment to prevent this side effect, which may be severe. Audiometric analysis may be necessary to assess the severity of ototoxicity. Other drugs (such as the aminoglycoside antibiotic class) may also cause ototoxicity, and the administration of this class of antibiotics in patients receiving cisplatin is generally avoided. The ototoxicity of both the aminoglycosides and cisplatin may be related to their ability to bind to melanin in the stria vascularis of the inner ear or the generation of reactive oxygen species.
Cisplatin can cause hypomagnesaemia, hypokalaemia and hypocalcaemia. The hypocalcaemia seems to occur in those with low serum magnesium secondary to cisplatin, so it is not primarily due to the Cisplatin. Cisplatin can also cause profound bone marrow suppression.

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Methotrexate, abbreviated MTX, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, and ectopic pregnancy. It acts by inhibiting the metabolism of folic acid. Methotrexate began to replace the more toxic antifolate aminopterin starting in the 1950s. Methotrexate was originally developed and continues to be used for chemotherapy either alone or in combination with other agents. It is effective for the treatment of a number of cancers including: breast, head and neck, leukemia, lymphoma, lung, osteosarcoma, bladder, and trophoblastic neoplasms.

Intravenous methotrexate doses more than 400 mg/m2 generally require rescue calcium folinate therapy. Such high doses should be monitored by an oncologist. In rare cases, high-dose intravenous methotrexate can cause acute kidney failure. This is a life threatening toxicity and immediate treatment with antidotal therapy is indicated.

Leucovorin Rescue
Methotrexate therapy causes cancer cells to develop a folic acid deficiency and die. However, normal cells also are affected by folic acid deficiency. As a result, patients treated with drugs such as methotrexate often develop blood disorders and other toxic side effects. When these patients are given leucovorin, it goes into normal cells and rescues them from the toxic effects of the methotrexate. Leucovorin cannot enter cancer cells, however, and they continue to be killed by methotrexate.

Side effects
The most common adverse effects include: ulcerative stomatitis, low white blood cell count and thus predisposition to infection, nausea, abdominal pain, fatigue, fever, dizziness, acute pneumonitis and rarely pulmonary fibrosis.

Central nervous system reactions to methotrexate have been reported, especially when given via the intrathecal route which include myelopathies and leucoencephalopathies. It has a variety of cutaneous side effects, particularly when administered in high doses.

Generally, the more “nonspecific” action a pharmacological substance has, the more possible side effects can be expected. Methotrexate has, like all cytotoxic substances, a broad array of possible adverse effects.