Ifosfamide
Encyclopedia
Ifosfamide (also marketed as Mitoxana and Ifex) is a nitrogen mustard
alkylating agent
used in the treatment of cancer
.
It is sometimes abbreviated "IFO".
s, including:
which, when prepared for use in chemotherapy
becomes a clear, colorless fluid
. The delivery is intravenous.
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 in as little as an hour.
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
and chloral hydrate
. The symptoms of ifosfamide encephalopathy can range from mild (difficulty concentrating, fatigue), to moderate (delirium
, psychosis
), to severe (nonconvulsive status epilepticus, coma
). 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
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
, and dialysis
as a rescue modality.
Nitrogen mustard
The nitrogen mustards are cytotoxic chemotherapy agents similar to mustard gas. Although their common use is medicinal, in principle these compounds can also be deployed as chemical warfare agents. Nitrogen mustards are nonspecific DNA alkylating agents. Nitrogen mustard gas was stockpiled by...
alkylating agent
Alkylating antineoplastic agent
An alkylating antineoplastic agent is an alkylating agent used in cancer treatment that attaches an alkyl group to DNA.The alkyl group is attached to the guanine base of DNA, at the number 7 nitrogen atom of the purine ring....
used in the treatment of cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
.
It is sometimes abbreviated "IFO".
Uses
It is given as a treatment for a variety of cancerCancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
s, including:
- Testicular cancerTesticular cancerTesticular cancer is cancer that develops in the testicles, a part of the male reproductive system.In the United States, between 7,500 and 8,000 diagnoses of testicular cancer are made each year. In the UK, approximately 2,000 men are diagnosed each year. Over his lifetime, a man's risk of...
- Breast cancerBreast cancerBreast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
- LymphomaLymphomaLymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
(Hodgkin's and Non-Hodgkin's) - Soft tissue sarcomaSoft tissue sarcomaA soft-tissue sarcoma is a form of sarcoma that develops in connective tissue, though the term is sometimes applied to elements of the soft tissue that are not currently considered connective tissue.-Risk factors:...
- Osteogenic sarcoma (Bone cancer)
- Lung cancerLung cancerLung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...
- Cervical cancerCervical cancerCervical cancer is malignant neoplasm of the cervix uteri or cervical area. One of the most common symptoms is abnormal vaginal bleeding, but in some cases there may be no obvious symptoms until the cancer is in its advanced stages...
- Ovarian cancerOvarian cancerOvarian cancer is a cancerous growth arising from the ovary. Symptoms are frequently very subtle early on and may include: bloating, pelvic pain, difficulty eating and frequent urination, and are easily confused with other illnesses....
Administration
It is a white powderPowder (substance)
A powder is a dry,thick bulk solid composed of a large number of very fine particles that may flow freely when shaken or tilted. Powders are a special sub-class of granular materials, although the terms powder and granular are sometimes used to distinguish separate classes of material...
which, when prepared for use in chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
becomes a clear, colorless fluid
Fluid
In physics, a fluid is a substance that continually deforms under an applied shear stress. Fluids are a subset of the phases of matter and include liquids, gases, plasmas and, to some extent, plastic solids....
. The delivery is intravenous.
Ifosfamide is often used in conjunction with Mesna
Mesna
Mesna is an organosulfur compound. It is used in cancer chemotherapy involving cyclophosphamide and ifosfamide as an adjuvant. It is marketed by Baxter as Uromitexan and Mesnex...
to avoid internal bleeding
Internal bleeding
Internal bleeding is bleeding occurring inside the body. It can be a serious medical emergency depending on where it occurs , and can potentially cause death and cardiac arrest if proper medical treatment is not received quickly....
in the patient, in particular hemorrhagic cystitis
Hemorrhagic cystitis
Hemorrhagic cystitis or Haemorrhagic cystitis is diffuse inflammation of the bladder leading to dysuria, hematuria, and hemorrhage. The disease can occur as a complication of cyclophosphamide, ifosfamide and radiation therapy...
.
Ifosfamide is given quickly, and in some cases can be given in as little as an hour.
Toxicity
Hemorrhagic cystitis is rare when ifosfamide is given together with mesna.A common and dose-limiting side-effect is encephalopathy
Encephalopathy
Encephalopathy means disorder or disease of the brain. In modern usage, encephalopathy does not refer to a single disease, but rather to a syndrome of global brain dysfunction; this syndrome can be caused by many different illnesses.-Terminology:...
(brain dysfunction). It occurs in some form in up to 50% of people receiving the agent. The reaction is probably mediated by chloroacetaldehyde
Chloroacetaldehyde
Chloroacetaldehyde is the organic compound with the formula ClCH2CHO. Like some related compounds, it is highly electrophilic reagent and a potentially dangerous alkylating agent. The compound is not normally encountered in the anhydrous form, but rather as the hydrate , ClCH2CH2. ...
, one of the breakdown products of the ifosfamide molecule, which has chemical properties similar to acetaldehyde
Acetaldehyde
Acetaldehyde is an organic chemical compound with the formula CH3CHO or MeCHO. It is one of the most important aldehydes, occurring widely in nature and being produced on a large scale industrially. Acetaldehyde occurs naturally in coffee, bread, and ripe fruit, and is produced by plants as part...
and chloral hydrate
Chloral hydrate
Chloral hydrate is a sedative and hypnotic drug as well as a chemical reagent and precursor. The name chloral hydrate indicates that it is formed from chloral by the addition of one molecule of water. Its chemical formula is C2H3Cl3O2....
. The symptoms of ifosfamide encephalopathy can range from mild (difficulty concentrating, fatigue), to moderate (delirium
Delirium
Delirium or acute confusional state is a common and severe neuropsychiatric syndrome with core features of acute onset and fluctuating course, attentional deficits and generalized severe disorganization of behavior...
, psychosis
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
), to severe (nonconvulsive status epilepticus, coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
). 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
National Cancer Institute
The National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...
or the Meanwell criteria (grade I-IV). Previous brain problems and low levels of albumin
Albumin
Albumin refers generally to any protein that is water soluble, which is moderately soluble in concentrated salt solutions, and experiences heat denaturation. They are commonly found in blood plasma, and are unique to other blood proteins in that they are not glycosylated...
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
Methylene blue
Methylene blue is a heterocyclic aromatic chemical compound with the molecular formula C16H18N3SCl. It has many uses in a range of different fields, such as biology and chemistry. At room temperature it appears as a solid, odorless, dark green powder, that yields a blue solution when dissolved in...
, 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
Albumin
Albumin refers generally to any protein that is water soluble, which is moderately soluble in concentrated salt solutions, and experiences heat denaturation. They are commonly found in blood plasma, and are unique to other blood proteins in that they are not glycosylated...
and thiamine
Thiamine
Thiamine or thiamin or vitamin B1 , named as the "thio-vitamine" is a water-soluble vitamin of the B complex. First named aneurin for the detrimental neurological effects if not present in the diet, it was eventually assigned the generic descriptor name vitamin B1. Its phosphate derivatives are...
, and dialysis
Dialysis
In medicine, dialysis is a process for removing waste and excess water from the blood, and is primarily used to provide an artificial replacement for lost kidney function in people with renal failure...
as a rescue modality.