ThioTEPA
Encyclopedia
N,N'N'-triethylenethiophosphoramide (ThioTEPA or thiotepa) is an alkylating agent
used to treat cancer
.
ThioTEPA is an organophosphorus compound with the formula SP(NC2H4)3. It is an analogue of N,N',N
). This molecule features tetrahedral phosphorus and is structurally akin to phosphate
. It is derived from aziridine
and thiophosphoryl chloride
.
company in the early 1950's and was reported in 1953. ThioTEPA has been in use since the 1960s.
ThioTEPA has been designated as orphan drug
by the European Medicines Agency
on January 29, 2007, and by the United States
Food and Drug Administration
(FDA) on April 2, 2007, as a conditioning treatment prior to haematopoietic stem cell transplantation. The applicant for these orphan drug designations was the italian
company ADIENNE Pharma & Biotech, owner of the drug TEPADINA (INN
: thiotepa).
Thiotepa is indicated, in combination with other chemotherapy medicinal products:
Thiotepa has been previously used in the palliation of a wide variety of neoplastic diseases. The more consistent results have been seen in: adenocarcinoma
of the breast
, adenocarcinoma of the ovary
, superficial papillary carcinoma of the urinary bladder
and for controlling intracavitary effusions secondary to diffuse or localized neoplastic diseases of various serosal cavities.
Thiotepa main toxicity is myelosuppression. The most serious complication of excessive therapy is bone marrow depression, causing leukopenia
, thrombocytopenia
, and anemia
. Serious toxicity involving the hematologic, hepatic and respiratory system were considered as expected consequences of the conditioning regimen and transplant process.
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 to treat 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...
.
ThioTEPA is an organophosphorus compound with the formula SP(NC2H4)3. It is an analogue of N,N',N
Tepa
-External links:*...
). This molecule features tetrahedral phosphorus and is structurally akin to phosphate
Phosphate
A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...
. It is derived from aziridine
Aziridine
Aziridines are organic compounds containing the aziridine functional group, a three-membered heterocycle with one amine group and two methylene groups...
and thiophosphoryl chloride
Thiophosphoryl chloride
Thiophosphoryl chloride is an inorganic compound with the formula PSCl3. Thiophosphoryl chloride, PSCl3, is a fuming, colorless liquid with a pungent odor...
.
History and use
ThioTEPA was first developed by American CyanamidAmerican Cyanamid
American Cyanamid was a large, diversified, American chemical manufacturer, founded by Frank Washburn in 1907. It was the only United States firm manufacturing the polio vaccine of the Sabin type....
company in the early 1950's and was reported in 1953. ThioTEPA has been in use since the 1960s.
ThioTEPA has been designated as orphan drug
Orphan drug
An orphan drug is a pharmaceutical agent that has been developed specifically to treat a rare medical condition, the condition itself being referred to as an orphan disease...
by the European Medicines Agency
European Medicines Agency
The European Medicines Agency is a European agency for the evaluation of medicinal products. From 1995 to 2004, the European Medicines Agency was known as European Agency for the Evaluation of Medicinal Products.Roughly parallel to the U.S...
on January 29, 2007, and by the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
Food and Drug Administration
Food 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) on April 2, 2007, as a conditioning treatment prior to haematopoietic stem cell transplantation. The applicant for these orphan drug designations was the italian
Italy
Italy , officially the Italian Republic languages]] under the European Charter for Regional or Minority Languages. In each of these, Italy's official name is as follows:;;;;;;;;), is a unitary parliamentary republic in South-Central Europe. To the north it borders France, Switzerland, Austria and...
company ADIENNE Pharma & Biotech, owner of the drug TEPADINA (INN
International Nonproprietary Name
An International Nonproprietary Name is the official nonproprietary or generic name given to a pharmaceutical substance, as designated by the World Health Organization...
: thiotepa).
Thiotepa is indicated, in combination with other chemotherapy medicinal products:
- with or without total body irradiationTotal body irradiationTotal body irradiation is a form of radiotherapy used primarily as part of the preparative regimen for haematopoietic stem cell transplantation. As the name implies, TBI involves irradiation of the entire body, though in modern practice the lungs are often partially shielded to lower the risk of...
(TBI), as conditioning treatment prior to allogeneic or autologous haematopoietic progenitor cell transplantation (HPCT) in haematological diseases in adult and paediatric patients; - when high dose chemotherapy with HPCT support is appropriate for the treatment of solid tumours in adult and paediatric patients.
Thiotepa has been previously used in the palliation of a wide variety of neoplastic diseases. The more consistent results have been seen in: adenocarcinoma
Adenocarcinoma
Adenocarcinoma is a cancer of an epithelium that originates in glandular tissue. Epithelial tissue includes, but is not limited to, the surface layer of skin, glands and a variety of other tissue that lines the cavities and organs of the body. Epithelium can be derived embryologically from...
of the breast
Breast
The breast is the upper ventral region of the torso of a primate, in left and right sides, which in a female contains the mammary gland that secretes milk used to feed infants.Both men and women develop breasts from the same embryological tissues...
, adenocarcinoma of the ovary
Ovary
The ovary is an ovum-producing reproductive organ, often found in pairs as part of the vertebrate female reproductive system. Ovaries in anatomically female individuals are analogous to testes in anatomically male individuals, in that they are both gonads and endocrine glands.-Human anatomy:Ovaries...
, superficial papillary carcinoma of the urinary bladder
Urinary bladder
The urinary bladder is the organ that collects urine excreted by the kidneys before disposal by urination. A hollow muscular, and distensible organ, the bladder sits on the pelvic floor...
and for controlling intracavitary effusions secondary to diffuse or localized neoplastic diseases of various serosal cavities.
Thiotepa main toxicity is myelosuppression. The most serious complication of excessive therapy is bone marrow depression, causing leukopenia
Leukopenia
Leukopenia is a decrease in the number of white blood cells found in the blood, which places individuals at increased risk of infection....
, thrombocytopenia
Thrombocytopenia
Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
, and 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...
. Serious toxicity involving the hematologic, hepatic and respiratory system were considered as expected consequences of the conditioning regimen and transplant process.
External links
- Thiotepa Official FDA information, side effects and uses on Drugs.comDrugs.comDrugs.com is an online pharmaceutical encyclopedia which provides drug information for consumers and healthcare professionals primarily in the USA.-History:...
- Thiotepa on cancer.org