www.know_the_risk_of_5fu_chemotherapy.com

colorectal cancer and preparing for chemotherapy? ask about your risk of serious side effects


Resources

American Cancer Society

 

Find Support and Treatment:  http://www.cancer.org/treatment/index

 

Guide to Cancer Drugs, specifically 5-FU: http://www.cancer.org/treatment/treatmentsandsideeffects/guidetocancerdrugs/fluorouracil

 

This page encourages you to discuss conditions with your doctor before starting treatment and here is what is said about DPD deficiency:

 

"If you have ever been told you have a dihydropyrimidine dehydrogenase (DPD) deficiency. DPD is an enzyme the body uses to process this drug. This inborn genetic abnormality can cause extreme side effects if you use 5-FU (even on your skin) or capecitabine. DPD deficiency can be present without symptoms, so you may not know you have it until you get one of these drugs or are tested for it."

 

Pasted from <http://www.cancer.org/treatment/treatmentsandsideeffects/guidetocancerdrugs/fluorouracil>

 

This page also lists possible side effects for which you should be alert and not bashful about discussing with your doctor at the first sign of trouble.  If you think your reaction is not normal, do not ignore the problem.

 

Colon Cancer Alliance  www.ccalliance.org

Enter 5-FU into the website's global search tool to find info on topics Chemotherapy and Biologics (here it identifies the drugs and the side effects but it does not discuss the probability of severe toxic reactions), Treatment Side Effects (no grading of the toxic effects), and Personal Stories among other related topics.

 

Live Strong   www.livestrong.org

 

Good support organization to help prepare for treatment but lacks specifics for dealing with individual treatment regimens such as 5-FU.

 

StrongMom  https://www.strongmom.org/

 

"Our mission is to provide financial support for the Prettitore Family and to raise awareness of DPD deficiency while striving to make patient testing for DPD Deficiency a requirement prior to 5-FU based chemotherapy treatments."

 

US Food and Drug Administration (FDA)

 

The FDA publishes label warnings for drugs used in chemotherapy treatments.  

 

The package insert the FDA requires for Fluorouracil Intravenous use contains the following information:

 

Warning (Box Warning)

"It is recommended that fluorouracil be given only by or under the supervision

of a qualified physician who is experienced in cancer chemotherapy and who

is well versed in the use of potent antimetabolites. Because of the possibility

of severe toxic reactions, it is recommended that patients be hospitalized at

least during the initial course of therapy.

 

CONTRAINDICATIONS

"Fluorouracil therapy is contraindicated for patients in a poor nutritional state, those

with depressed bone marrow function, those with potentially serious infections or

those with a known hypersensitivity to fluorouracil.

 

WARNINGS (see boxed WARNING)

THE DAILY DOSE OF FLUOROURACIL IS NOT TO EXCEED 800 MG. IT IS

RECOMMENDED THAT PATIENTS BE HOSPITALIZED DURING THEIR FIRST

COURSE OF TREATMENT.

"Fluorouracil should be used with extreme caution in poor risk patients with a history

of high-dose pelvic irradiation or previous use of alkylating agents, those who have

a widespread involvement of bone marrow by metastatic tumors or those with

impaired hepatic or renal function.

 

"Rarely, unexpected, severe toxicity (e.g., stomatitis, diarrhea, neutropenia and

neurotoxicity) associated with 5-fluorouracil has been attributed to deficiency of

dihydropyrimidine dehydrogenase activity (emphasis added here).  A few patients have been rechallenged with 5-fluorouracil and despite 5-fluorouracil dose lowering, toxicity recurred and

progressed with worse morbidity.  Absence of this catabolic enzyme appears to

result in prolonged clearance of 5-fluorouracil.

 

"Pregnancy: Teratogenic Effects – Pregnancy Category D. Fluorouracil may cause

fetal harm when administered to a pregnant woman. Fluorouracil has been shown

to be teratogenic in laboratory animals. Fluorouracil exhibited maximum

teratogenicity when given to mice as single intraperitoneal injections of 10 to 40

mg/kg on day 10 or 12 of gestation. Similarly, intraperitoneal doses of 12 to 37

mg/kg given to rats between days 9 and 12 of gestation and intramuscular doses of

3 to 9 mg given to hamsters between days 8 and 11 of gestation were teratogenic.

Malformations included cleft palates, skeletal defects and deformed appendages,

paws and tails. The dosages which were teratogenic in animals are 1 to 3 times the

maximum recommended human therapeutic dose. In monkeys, divided doses of 40

mg/kg given between days 20 and 24 of gestation were not teratogenic.

 

"There are no adequate and well-controlled studies with fluorouracil in pregnant

women. While there is no evidence of teratogenicity in humans due to fluorouracil,

it should be kept in mind that other drugs which inhibit DNA synthesis (e.g.,

methotrexate and aminopterin) have been reported to be teratogenic in humans.

Women of childbearing potential should be advised to avoid becoming pregnant. If

the drug is used during pregnancy, or if the patient becomes pregnant while taking

the drug, the patient should be told of the potential hazard to the fetus. Fluorouracil

should be used during pregnancy only if the potential benefit justifies the potential

risk to the fetus.

 

"Combination Therapy: Any form of therapy which adds to the stress of the patient,

interferes with nutrition or depresses bone marrow function will increase the

toxicity of fluorouracil.

 

PRECAUTIONS

"General: Fluorouracil is a highly toxic drug with a narrow margin of safety.

Therefore, patients should be carefully supervised, since therapeutic response is

unlikely to occur without some evidence of toxicity. Severe hematological toxicity,

gastrointestinal hemorrhage and even death may result from the use of fluorouracil

despite meticulous selection of patients and careful adjustment of dosage. Although

severe toxicity is more likely in poor risk patients, fatalities may be encountered

occasionally even in patients in relatively good condition.

Therapy is to be discontinued promptly whenever one of the following signs of

toxicity appears:

Stomatitis or esophagopharyngitis, at the first visible sign.

Leukopenia (WBC under 3500) or a rapidly falling white blood count.

Vomiting, intractable.

Diarrhea, frequent bowel movements or watery stools.

Gastrointestinal ulceration and bleeding.

Thrombocytopenia (platelets under 100,000).

Hemorrhage from any site.

 

"The administration of 5-fluorouracil has been associated with the occurrence of

palmar-plantar erythrodysesthesia syndrome, also known as hand-foot syndrome.

This syndrome has been characterized as a tingling sensation of hands and feet

which progress over the next few days to pain when holding objects or walking. The

palms and soles became symmetrically swollen and erythematous with tenderness

of the distal phalanges, possibly accompanied by desquamation. Interruption of

therapy is followed by gradual resolution over 5 to 7 days. Although pyridoxine has

been reported to ameliorate the palmar-plantar erythrodysesthesia syndrome, its

safety and effectiveness has not been established."

 

The package insert the FDA requires for Xeloda use contains the following information:

 

Contraindications (in other words, not to be used when the following conditions are known)

• "Dihydropyrimidine dehydrogenase (DPD) deficiency

• Severe Renal Impairment

• Hypersensitivity

 

Warnings and Precautions

• "Diarrhea: May be severe. Interrupt XELODA treatment immediately until diarrhea resolves or decreases to grade 1. Recommend standard antidiarrheal treatments.

• Coagulopathy: May result in bleeding, death. Monitor anticoagulant response (e.g., INR) and adjust anticoagulant dose accordingly.

• Cardiotoxicity: Common in patients with a prior history of coronary artery disease.

• Pregnancy: Can cause fetal harm. Advise women of the potential risk to the fetus.

• Hand-and-Foot Syndrome (Grade 2 or 3): Interrupt XELODA treatment until the event resolves or decreases in intensity.

• Hyperbilirubinemia (Grade 2 to 4): Interrupt XELODA treatment immediately until the hyperbilirubinemia resolves or decreases in intensity.

• Hematologic: Do not treat patients with neutrophil counts <1.5 x 109/L or thrombocyte counts <100 x 109/L. If grade 3-4 neutropenia or thrombocytopenia occurs, stop therapy until condition resolves.

 

Adverse Reactions

"Most common adverse reactions (≥30%) were diarrhea, hand-and-foot syndrome, nausea, vomiting, abdominal pain, fatigue/weakness, and hyperbilirubinemia. Other adverse reactions, including serious adverse reactions, have been reported."

 

 National Comprehensive Cancer Network (NCCN)  http://www.nccn.org/professionals/physician_gls/f_guidelines.asp

 

This site contains guidelines oncologists rely upon to detect and treat all forms of cancer.  The guidelines for treating colon, rectal, anal, breast, head/neck cancers do not contain warnings concerning the risk of treating DPD deficient patients with 5-FU -- see also Petitions.