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 Thiotepa

DRUG DESCRIPTION

Thiotepa for Injection USP is an ethylenimine-type compound. It is supplied as a non-pyrogenic, sterile Iyophilized powder for intravenous, intracavitary or intravesical administration, containing 15 mg of thiotepa. Thiotepa is a synthetic product with antitumor activity. The chemical name for thiotepa is Tris (1-aziridinyl) phosphine sulfide.   Thiotepa has the molecular formula C6H12N3PS, and a molecular weight of 189.22. When reconstituted with Sterile Water for Injection, the resulting solution has a pH of approximately 5.5 to 7.5. Thiotepa is stable in alkaline medium and unstable in acid medium.

CLINICAL PHARMACOLOGY

Thiotepa is a cytotoxic agent of the polyfunctional type, related chemically and pharmacologically to nitrogen mustard. The radiomimetic action of thiotepa is believed to occur through the release of ethylenimine radicals which, like irradiation, disrupt the bonds of DNA. One of the principal bond disruptions is initiated by alkylation of guanine at the N-7 position, which severs the linkage between the purine base and the sugar and liberates alkylated guanines.

History and use

ThioTEPA was first developed by American Cyanamid company in the early 1950's and was reported in 1953[2]. 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:

(a) with or without total body irradiation (TBI), as conditioning treatment prior to allogeneic or autologous haematopoietic progenitor cell transplantation (HPCT) in haematological diseases in adult and paediatric patients;
 (b) 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 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. From http://en.wikipedia.org/wiki/Thiotepa.

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