Carmustine
Encyclopedia
Carmustine or BCNU is a mustard gas
-related β-chloro-nitrosourea compound
used as an alkylating agent
in chemotherapy
. As a dialkylating agent, BCNU is able to form interstrand crosslinks in DNA which prevents DNA replication and DNA transcription.
It has the appearance of a orange-yellow solid.
Carmustine for injection is marketed under the name BiCNU by Bristol-Myers Squibb.
, glioblastoma multiforme
, medulloblastoma
and astrocytoma
), multiple myeloma
and lymphoma
(Hodgkin's
and non-Hodgkin
). BCNU is sometimes used in conjunction with alkyl guanine transferase (AGT) inhibitors, such as O6-benzylguanine. The AGT-inhibitors increase the efficacy of BCNU by inhibiting the Direct Reversal pathway of DNA repair, which will prevent formation of the interstrand crosslink
between the N1 of guanine
and the N3 of cytosine
.
Cases of fatal pulmonary toxicity have been reported.
Delayed onset pulmonary fibrosis
Cumulative myelosuppression, manifested by more depressed indices.
Anemia
also occurs, but is less frequent and less severe than thrombocytopenia or leukopenia.
The occurrence of acute leukemia and bone marrow dysplasias have been reported in patients following long-term nitrosourea therapy.
and vomiting after IV administration are noted frequently. This usually occurs within 2 hours of administration. This is usually dose related. Prior administration of antiemetics is effective in diminishing and sometimes preventing side effects.
(FDA) approved biodegradable discs, Gliadel, infused with carmustine can be used. They are implanted under the skull during a surgery called a craniotomy
.
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...
-related β-chloro-nitrosourea compound
Nitrosourea compounds
Nitrosourea is both the name of a molecule, and a class of compounds that include a nitroso group and a urea.-Examples:Examples include:* Carmustine* Lomustine* Semustine* Ethylnitrosourea * Streptozotocin...
used as an 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....
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....
. As a dialkylating agent, BCNU is able to form interstrand crosslinks in DNA which prevents DNA replication and DNA transcription.
It has the appearance of a orange-yellow solid.
Carmustine for injection is marketed under the name BiCNU by Bristol-Myers Squibb.
Uses
It is used in the treatment of several types of brain cancer (including gliomaGlioma
A glioma is a type of tumor that starts in the brain or spine. It is called a glioma because it arises from glial cells. The most common site of gliomas is the brain.-By type of cell:...
, glioblastoma multiforme
Glioblastoma multiforme
Glioblastoma multiforme is the most common and most aggressive malignant primary brain tumor in humans, involving glial cells and accounting for 52% of all functional tissue brain tumor cases and 20% of all intracranial tumors. Despite being the most prevalent form of primary brain tumor, GBMs...
, medulloblastoma
Medulloblastoma
Medulloblastoma is a highly malignant primary brain tumor that originates in the cerebellum or posterior fossa.Previously, medulloblastomas were thought to represent a subset of primitive neuroectodermal tumor of the posterior fossa...
and astrocytoma
Astrocytoma
Astrocytomas are a type of neoplasm of the brain. They originate in a particular kind of glial-cells, star-shaped brain cells in the cerebrum called astrocytes. This type of tumor does not usually spread outside the brain and spinal cord and it does not usually affect other organs...
), multiple myeloma
Multiple myeloma
Multiple myeloma , also known as plasma cell myeloma or Kahler's disease , is a cancer of plasma cells, a type of white blood cell normally responsible for the production of antibodies...
and lymphoma
Lymphoma
Lymphoma 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
Hodgkin's lymphoma
Hodgkin's lymphoma, previously known as Hodgkin's disease, is a type of lymphoma, which is a cancer originating from white blood cells called lymphocytes...
and non-Hodgkin
Non-Hodgkin lymphoma
The non-Hodgkin lymphomas are a diverse group of blood cancers that include any kind of lymphoma except Hodgkin's lymphomas. Types of NHL vary significantly in their severity, from indolent to very aggressive....
). BCNU is sometimes used in conjunction with alkyl guanine transferase (AGT) inhibitors, such as O6-benzylguanine. The AGT-inhibitors increase the efficacy of BCNU by inhibiting the Direct Reversal pathway of DNA repair, which will prevent formation of the interstrand crosslink
Crosslinking of DNA
Crosslinks in DNA occur when various exogenous or endogenous agents react with two different positions in the DNA. This can either occur in the same strand or in the opposite strands of the DNA . Crosslinks also occur between DNA and protein...
between the N1 of guanine
Guanine
Guanine is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine . In DNA, guanine is paired with cytosine. With the formula C5H5N5O, guanine is a derivative of purine, consisting of a fused pyrimidine-imidazole ring system with...
and the N3 of cytosine
Cytosine
Cytosine is one of the four main bases found in DNA and RNA, along with adenine, guanine, and thymine . It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached . The nucleoside of cytosine is cytidine...
.
Side effects
Bone marrow may take 6 weeks to recover function following treatment with carmustine. Weekly monitoring of platelet and white blood cell counts are recommended as a basis for patient-specific adjustments to dosage regimens. Bone marrow and pulmonary toxicities are a function of lifetime cumulative dose.Pulmonary toxicity
Pulmonary toxicity characterised by pulmonary infiltrates and/or fibrosis (scarring of the lungs).Cases of fatal pulmonary toxicity have been reported.
Delayed onset pulmonary fibrosis
Hematologic toxicity
Delayed myelosuppression. Thrombocytopenia usually occurs about 4 weeks post administration. Leukopenia occurs approximately 5–6 weeks after administration.Cumulative myelosuppression, manifested by more depressed indices.
Anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
also occurs, but is less frequent and less severe than thrombocytopenia or leukopenia.
The occurrence of acute leukemia and bone marrow dysplasias have been reported in patients following long-term nitrosourea therapy.
Gastrointestinal toxicity
NauseaNausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
and vomiting after IV administration are noted frequently. This usually occurs within 2 hours of administration. This is usually dose related. Prior administration of antiemetics is effective in diminishing and sometimes preventing side effects.
Hepatotoxicity
A reversible type of hepatic toxicity, manifested by increased transaminase, alkaline phosphatase and bilirubin levels, has been reported in a small percentage of patients.Nephrotoxicity
Renal abnormalities consisting of progressive azotemia, decrease in kidney size and renal failure have been reported in patients who received large cumulative doses after prolonged therapy. Kidney damage has also been reported occasionally in patients receiving lower total doses.Implants
In the treatment of brain tumours, the U.S. Food and Drug AdministrationFood and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) approved biodegradable discs, Gliadel, infused with carmustine can be used. They are implanted under the skull during a surgery called a craniotomy
Craniotomy
A craniotomy is a surgical operation in which a bone flap is temporarily removed from the skull to access the brain. Craniotomies are often a critical operation performed on patients recording, brain imaging, and for neurological manipulations such as electrical stimulation and chemical...
.
External links
- BiCNU (package insert; U.S.)