Ifosfamide, sold under the brand name Ifex among others, is a chemotherapy medication used to treat a number of types of cancer. This includes

testicular cancer Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system. Symptoms may include a lump in the testicle or swelling or pain in the scrotum. Treatment may result in infertility. Risk factors include an c ...

, soft tissue sarcoma,

osteosarcoma An osteosarcoma (OS) or osteogenic sarcoma (OGS) is a cancerous tumor in a bone. Specifically, it is an aggressive malignant neoplasm that arises from primitive transformed cells of mesenchyme, mesenchymal origin (and thus a sarcoma) and that exhi ...

, bladder cancer, small cell lung cancer, cervical cancer, and ovarian cancer. It is administered by injection into a vein. Common side effects include hair loss, vomiting, blood in the urine, infections, and kidney problems. Other severe side effects include bone marrow suppression and decreased level of consciousness. Use during

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

will likely result in harm to the baby. Ifosfamide is in the alkylating agent and

nitrogen mustard Nitrogen mustards (NMs) are cytotoxic organic compounds with the bis(2-chloroethyl)amino ((ClC2H4)2NR) functional group. Although originally produced as chemical warfare agents, they were the first chemotherapeutic agents for treatment of canc ...

family of medications. It works by disrupting the duplication of

DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

and the creation of

RNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...

. Ifosfamide was approved for medical use in the United States in 1987. It is on the World Health Organization's List of Essential Medicines.

Medical uses

It is given as a treatment for a variety of

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

s, including: *

Testicular cancer Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system. Symptoms may include a lump in the testicle or swelling or pain in the scrotum. Treatment may result in infertility. Risk factors include an c ...

Breast cancer Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...

* Lymphoma (Hodgkin and non-Hodgkin) * Soft tissue sarcoma *

Osteosarcoma An osteosarcoma (OS) or osteogenic sarcoma (OGS) is a cancerous tumor in a bone. Specifically, it is an aggressive malignant neoplasm that arises from primitive transformed cells of mesenchyme, mesenchymal origin (and thus a sarcoma) and that exhi ...

or bone tumor * Lung cancer * Cervical cancer * Ovarian cancer

Administration

It is a white powder which, when prepared for use in

chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

, becomes a clear, colorless fluid. The delivery is

intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...

. Ifosfamide is often used in conjunction with mesna to avoid internal bleeding in the patient, in particular hemorrhagic cystitis. Ifosfamide is given quickly, and in some cases can be given as quickly as an hour.

Mechanism of action

Ifosfamide is a DNA-damaging alkylating agent, belonging to the same class of chemotherapy drugs as cyclophosphamide. It is a prodrug, meaning that It has to be converted by CYP450 into its main active metabolites-(Iso)phosphoramide mustards. These metabolites form DNA cross links mainly at Guanine N-7 positions.

Side effects

Hemorrhagic cystitis is rare when ifosfamide is given with mesna. A common and dose-limiting side effect is encephalopathy (brain dysfunction). It occurs in some form in up to 50% of people receiving the agent. The reaction is probably mediated by chloroacetaldehyde, one of the breakdown products of the ifosfamide molecule, which has chemical properties similar to

acetaldehyde Acetaldehyde (IUPAC systematic name ethanal) is an organic compound, organic chemical compound with the chemical formula, formula , sometimes abbreviated as . It is a colorless liquid or gas, boiling near room temperature. It is one of the most ...

and

chloral hydrate Chloral hydrate is a geminal diol with the formula . It was first used as a sedative and hypnotic in Germany in the 1870s. Over time it was replaced by safer and more effective alternatives but it remained in use in the United States until at ...

. The symptoms of ifosfamide encephalopathy can range from mild (difficulty concentrating, fatigue), to moderate ( delirium,

psychosis In psychopathology, psychosis is a condition in which a person is unable to distinguish, in their experience of life, between what is and is not real. Examples of psychotic symptoms are delusions, hallucinations, and disorganized or inco ...

), to severe ( nonconvulsive status epilepticus or

coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to Nociception, respond normally to Pain, painful stimuli, light, or sound, lacks a normal Circadian rhythm, sleep-wake cycle and does not initiate ...

). In children, this can interfere with neurological development. Apart from the brain, ifosfamide can also affect peripheral nerves. The severity of the reaction can be classified according to either the

National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...

or the Meanwell criteria (grade I–IV). Previous brain problems and low levels of albumin in the blood increase the likelihood of ifosfamide encephalopathy. In most cases, the reaction resolves spontaneously within 72 hours. If it develops during an infusion of the drug, discontinuing the infusion is advised. The most effective treatment for severe (grade III–IV) encephalopathy is an intravenous solution of methylene blue, which appears to shorten the duration of encephalopathy; the exact mechanism of action of methylene blue is unclear. In some cases, methylene blue may be used as a prophylaxis before further doses of ifosfamide are administered. Other treatments include albumin and

thiamine Thiamine, also known as thiamin and vitamin B1, is a vitamin – an Nutrient#Micronutrients, essential micronutrient for humans and animals. It is found in food and commercially synthesized to be a dietary supplement or medication. Phosp ...

, and dialysis as a rescue modality. Ifosfamide may also cause a normal anion gap acidosis, specifically renal tubular acidosis type 2.

References

{{Authority control Oxazaphosphinans Nitrogen mustards Phosphorodiamidates Chloroethyl compounds World Health Organization essential medicines Wikipedia medicine articles ready to translate