Chemotherapy Drugs (Dox - Me)

Doxorubicin (Adriamycin): short intravenous push infusions and intravenous bolus injections are common methods for the administration of Adriamycin. Continuous intravenous infusions of this drug have also been utilized. Side effects include bone marrow suppression, stomatitis (sores around the mouth area), nausea and vomiting and rarely diarrhea. Hyperpigmentation of the skin and discoloration of the nail beds may occur and inflammation of the eyes with excessive tearing has also been seen. Marked hair loss occurs. As with Daunorubicin, reactivation of soft tissue reactions in areas previously receiving radiotherapy (radiation recall effect) may occur.

Extravasation of this material is known to produce local skin and deep tissue damage at the site of leakage. Ulcers may result in up to 33% of patients experiencing extravasation. These ulcers do not heal, therefore early surgical intervention and skin grafting are recommended. Numerous antidotes have been tried but only topical application of DMSO (dimethylsulfoxide) has been found helpful. Cold packs may also be of benefit in this situation.

A potential toxic effect of Doxorubicin administration is the development of cardiotoxicity. There is an acute, non dose related toxicity called myocarditis-pericarditis syndrome (the development of inflammation of the heart muscle and sack surrounding the heart), which rarely occurs. Additionally, there is the delayed, cumulative total dose related, development of cardiomyopathy. This is usually an irreversible event although it can be managed with standard medical therapy. Risk factors for the development of this toxicity include cumulative total doses greater than 550 mg/m2, age greater than 70 years, previous radiation to the heart and preexisting heart disease such as previous heart attack or long standing high blood pressure.

Etoposide (VP-16, VePesid): administration is via intravenous infusion over at least 30 minutes. Severe hypotension (low blood pressure) may occur if the drug is given too rapidly. The drug may also be given via pill form. Although this drug is not considered a vesicant (as Daunorubicin and Doxorubicin are), extravasation should be avoided.

The principal toxic effects of this drug are bone marrow suppression. However, nausea and vomiting, and anorexia (loss of appetite) can occur although associated more with the oral administration of the drug. Other adverse effects include hair loss (alopecia), headache, fever and low blood pressure. There have been some reported cases of cardiotoxicity including heart attack and congestive heart failure. Rarely (3%), neurotoxicity has been reported. This has consisted of fatigue and sleepiness and more rarely the development of peripheral neuropathy (tingling and numbness of the hands and/or feet). Lastly, there are some indications that this drug may increase the risk of developing leukemia (leukomogenic), which varies between 2-12%.

5-Flourouracil (5-FU): administered as an intravenous push or as a continuous infusion; may also be used intraperitoneal (inside the abdominal cavity) as a short infusion. Side effects include nausea and vomiting, mouth sores (mucositis and stomatitis), diarrhea, inflammation of the esophagus and gastric ulcerations (seen with continuous infusion therapy). Decreased white count may occasionally occur as well as hair loss and discoloration of the nail beds. The skin may become more sensitive to the sun and sun avoidance is recommended. Neurotoxicity may also be seen and is manifested by headache, minor visual disturbances and inability to walk without losing balance (cerebellar ataxia). Additionally, there have been reported cases of cardiotoxicity including heart attacks, chest pain (angina), sudden death and irregular heart beats. The mechanism of the heart toxicity is no known.

Lastly, a syndrome called the hand-foot syndrome may occur and consists of severe skin rash with skin peeling and the development of erythema (inflammation) and hypersensitivity (dysethesias) of the skin. The syndrome usually responds to temporary discontinuation of the 5-FU and administration of pyridoxine.

Fludarabine (Fludara): administered as a short intravenous infusion over 30 minutes. There have been no episodes of extravasation injuries noted. Side effects include bone marrow suppression (with decreased white count and platelets predominating). However, there is significant depression of the lymphocytic series with decreased helper and suppressor cell types. This leads to a functional immunosuppression with increased risk of developing opportunistic infections. Other effects include nausea and vomiting, diarrhea (30% of patients) and mild, transient liver and kidney dysfunction. Rare side effects include sleepiness and skin rash. Inflammation of the lung (interstitial pneumonitis) may rarely occur and spontaneously resolves over the course of several weeks with or without steroids.

Gemcitabine (Gemzar): administered as an intravenous infusion over 30 minutes. Side effects include bone marrow suppression with decreased platelets predominating (leading to increased risk of bleeding). Other effects include a reversible skin rash, fever, nausea and vomiting and the development of a flu-like syndrome.

Herceptin (Trastuzumab; anti-HER 2 monoclonal antibody): administered intravenously. When given alone, side effects include diarrhea, chills, fevers, headache, dizziness, lowered blood pressure, and rash. Rare effects include lowered blood counts, pain and generalized feeling of unease.

When given in combination with chemotherapy cardiotoxicity was significantly increased. Symptoms included the development of shortness of breath, edema, cough and decreased heart muscle function as measured by evaluation of ventricular function. It has been noted that the development of cardiotoxicity is highest in those individuals receiving Herceptin and chemotherapy- particularly cytoxan and adriamycin. Other effects seen in combination therapy include an increased risk of developing mild to moderate upper respiratory infections.

Hydroxyurea (Hydrea): usually administered orally as a single daily dose. The major adverse effect is bone marrow suppression (leading to increased risk of infection), which is dose related in severity and onset. Other symptoms include nausea and vomiting, diarrhea, constipation and rarely stomatitis. Skin reactions including rash, facial redness and recall of erythema (redness) and hyperpigmentation of previously radiated tissues can be seen. Neurologic toxicity including headache, dizziness, confusion, hallucinations and convulsions have been reported. Hair loss is rare.

Ifosfamide (Ifex): usually administered intravenously as a short infusion; however, doses may also be infused over 30 minutes or by continuous infusion over 120 hours. The use of Mesna concurrently is required to prevent severe hematuria (bloody urine) from high-dose Ifosfamide therapy. Regardless of dose adequate hydration is required to decrease the incidence of drug induced hemorrhagic cystitis.

Extravasation should not cause severe tissue necrosis (death), as the agent is inactive prior to metabolism in the liver.

Urinary tract toxicity is the dose limiting side-effect of Ifex. The incidence of this complication is higher than with Cyclophosphamide. Hair loss is commonly seen; additionally, nausea and vomiting and bone marrow suppression have been seen. With high doses of Ifex one can see neurological toxicity. Seizures, problems walking and weakness have all been reported.

Irinotecan (CPT-11): administered intravenously. Dose limiting side effects include diarrhea and decreased white counts (leading to increased risk of infection). Other effects include nausea and vomiting and hair loss. Rarely, pulmonary infiltrates with associated fever and shortness of breath may occur. Treatment with steroids is usually beneficial.

Melphelan (Alkeran): administered as a pill. Absorption is improved if taken on an empty stomach. Bone marrow suppression is the major side effect of this drug. Evidence suggests that long term oral dosing can increase the chance of developing myelodysplasia or acute leukemia. Other infrequent effects include hair loss, stomatitis, dermatitis and pulmonary fibrosis. Severe hypersensitivity reactions with low blood pressure, sweating, and heart problems have been reported.

Methotrexate (MTX): administration may be either by mouth, intramuscular, intravenous (either as a infusion or as a push), intra-arterial and intrathecal (into the area surrounding the brain). Bone marrow suppression (with increased risk of bleeding, infection and shortness of breath) may occur. Nausea, vomiting and loss of appetite may occur. Other symptoms such as gingivitis (inflammation of the gums of the mouth), pharyngitis and mucosal ulceration have also been seen. Liver dysfunction may also occur; as well as, skin rashes, itchiness, depigmentation, hyperpigmentation, hair loss and increased sensitivity to light. Renal failure is also a possibility with high dose MTX therapy. Lastly, dizziness, blurred vision and confusion may occur, as well as chills, fever and the potential development of pulmonary scarring (fibrosis) or inflammation (pneumonitis).

Publication Review By: Stanley J. Swierzewski, III, M.D.

Published: 15 Aug 1999

Last Modified: 13 Oct 2011