Thiotepa

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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Synonym(s)

CAS number: 52-24-4; N,N',N" -triethylene ethophosphoramide; ThioTEPA

Definition
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Thiotepa, an ethyleneimine compound (molecular formula: C6H12N3PS), acts as an alkylating (see below alkylans), non-selective cytotoxic cytostatic agent. Since Thiotepa, in contrast to the nitrogen-lost DErivates , is already present in an effective form (no prodrug), the drug is suitable for local instillation (and application) in addition to its parenteral application.

Half-life
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2,5 h

Indication
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Systemic applications:

  • Breast and ovarian cancer, chronic leukemia, Hodgkin's disease, as high-dose therapy also for brain tumours.
  • Thiotepa is used in combination with other chemotherapeutic agents with or without whole body irradiation (TBI) for conditioning prior to allogeneic or autologous hematopoietic stem cell transplantation (HSCT) for the treatment of hematological diseases in adults and children

Local applications:

  • Topical application for condylomata acuminata.
  • Also topical: bladder carcinoma, malignant pleural effusions

Pregnancy/nursing period
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Women of childbearing age must use a reliable method of contraception during treatment, and a pregnancy test should be carried out before starting treatment.

Pregnancy: Pre-clinical studies have shown that Thiotepa, like most alkylants, causes embryofetal lethality and teratogenicity. Thiotepa is therefore contraindicated during pregnancy.

Lactation: It is unknown whether Thiotepa passes into breast milk. Due to its pharmacological properties and potential toxicity to breastfed newborns/infants, breastfeeding during treatment with Thiotepa is contraindicated.

Fertility: Like most alkylancias, Thiotepa may affect fertility in both women and men. Male patients should consider cryopreservation of sperm before starting treatment and should not conceive a child during treatment or for a year afterwards.

Dosage and method of use
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Systemic:

  • Haematological diseases: The recommended dose for haematological diseases is 125 mg/m2/day (3.38 mg/kg/day) to 300 mg/m2/day (8.10 mg/kg/day) as a once-daily infusion for 2 to 4 consecutive days prior to autologous HSCT, depending on the combination with other chemotherapeutic agents, without exceeding the maximum cumulative dose of 900 mg/m2 (24.32 mg/kg) throughout the duration of conditioning.
  • Lymphoma: The recommended dose is 125 mg/m2/day (3.38 mg/kg/day) to 300 mg/m2/day (8.10 mg/kg/day) as a once-daily infusion on 2 to 4 consecutive days prior to autologous HSCT, depending on the combination with other chemotherapeutic agents, without exceeding the maximum cumulative dose of 900 mg/m2 (24.32 mg/kg) throughout the duration of conditioning.
  • Multiple Myeloma: The recommended dose is 150 mg/m2/day (4.05 mg/kg/day) to 250 mg/m2/day (6.76 mg/kg/day) as a once-daily infusion for 3 consecutive days prior to autologous HSCT, depending on the combination with other chemotherapeutic agents, without exceeding the maximum cumulative dose of 750 mg/m2 (20.27 mg/kg) throughout the duration of conditioning.
  • Solid tumors: The recommended dose for solid tumors is 120 mg/m2/day (3.24 mg/kg/day) to 250 mg/m2/day (6.76 mg/kg/day), divided into one or two daily infusions on 2 to 5 consecutive days prior to autologous HSCT, depending on the combination with other chemotherapeutic agents, without exceeding the maximum cumulative dose of 800 mg/m2 (21.62 mg/kg) throughout the duration of conditioning.
  • For further doses see Technical Information

Local for Condylomata acuminata

  • Brush on undiluted solution thinly once a week.

Undesirable effects
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Fever, local irritation, pruritus, urticaria. Systemic NW not known.

Contraindication
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Hypersensitivity to the active substance.

Pregnancy and lactation

Simultaneous use with yellow fever vaccine and with live viral and bacterial vaccines

In general, live viral and bacterial vaccines must not be administered to patients treated with immunosuppressive chemotherapeutic agents. There must be at least three months between the end of therapy and vaccination.

Phenytoin: risk of aggravation of convulsions due to reduced absorption of phenytoin in the digestive tract by cytostatic drugs or risk of increased toxicity and loss of efficacy of the cytostatic drug due to increased metabolism in the liver by phenytoin.

Preparations
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Thiotepa Lederle®

Note(s)
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Thiotepa was originally developed as an auxiliary substance in cotton production

The result of treatment with Thiotepa at the recommended dose and with the recommended treatment regimen is marked myelosuppression in all patients. Severe granulocytopenia, thrombocytopenia and anaemia may occur alone or in combination.

Thiotepa may cause pulmonary toxicity, which may increase the pulmonary toxicity of other cytostatic drugs (busulfan, fludarabine and cyclophosphamide).

Previous brain irradiation or craniospinal irradiation may promote severe toxic reactions (such as encephalopathy).

Simultaneous use with attenuated live vaccines (except yellow fever vaccines), phenytoin and fosphenytoin is not recommended.

Like most alkylants, Thiotepa can affect fertility in both men and women. Male patients should consider cryopreservation of sperm before starting therapy and should not conceive a child during treatment or for a year afterwards.

Literature
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  1. Technical Information Thiotepa® Lederle
  2. Maanen MJ et al (2000) Chemistry, pharmacology and pharmacokinetics of N,N',N" -triethylene ethophosphoramide (ThioTEPA). Cancer Treat Rev 26:257-268.
  3. Van Schandevyl G et al (2019) Thiotepa-induced cutaneous toxicity in pediatric patients: Case report and implementation of preventive care guidelines. J Oncol Pharm Pract 25:689-693.

Authors

Last updated on: 29.10.2020