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Thiotepa is an old chemotherapy with a modern job: at high doses it prepares patients for stem cell transplants, and it is still instilled into the bladder or body cavities for superficial bladder cancer and malignant effusions.
Thiotepa was first approved in 1959 for adenocarcinoma of the breast or ovary, superficial papillary carcinoma of the urinary bladder and control of malignant intracavitary effusions. Tepadina (approved 2017 in the US, 2010 in the EU) added conditioning before allogeneic haematopoietic stem cell transplantation, initially for children with class 3 beta-thalassaemia in the US and, in the EU, for haematological and solid tumours in adults and children. In practice thiotepa-based regimens (TBC, thiotepa-busulfan-fludarabine) are standard before autologous transplant in primary CNS lymphoma and in cord blood and haploidentical transplantation. Profound myelosuppression, mucositis and skin toxicity from sweat excretion (patients bathe frequently) are the main issues.
Polyfunctional alkylating agent related to nitrogen mustard; releases ethyleneimine radicals that cross-link DNA. Crosses the blood-brain barrier, which underlies its use in CNS lymphoma conditioning.
1.Thiotepa slips into a pocket on its target.
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| Region | Year | Indication |
|---|---|---|
| US | 1959 | Breast and ovarian adenocarcinoma; superficial papillary bladder carcinoma (intravesical); malignant effusions |
| US | 2017 | Conditioning before allogeneic HSCT for class 3 beta-thalassaemia in children (Tepadina) |
| EU | 2010 | Conditioning before haematopoietic progenitor cell transplantation for haematological diseases and solid tumours (Tepadina) |
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High-dose chemotherapy with autologous transplant is the preferred consolidation for fit patients with primary CNS lymphoma who complete MATRix induction.
Autologous transplant is an effective consolidation that avoids the neurotoxicity of whole-brain radiotherapy, and IELSG43 later showed it beats non-myeloablative consolidation.
MATRix became the reference induction for fit patients with primary CNS lymphoma and the control arm of later randomised trials.
Query for this drug: (TITLE:"Thiotepa" OR ABSTRACT:"Thiotepa" OR TITLE:"Tepadina" OR ABSTRACT:"Tepadina" OR TITLE:"Thioplex historic" OR ABSTRACT:"Thioplex historic" OR TITLE:"Triethylenethiophosphoramide" OR ABSTRACT:"Triethylenethiophosphoramide") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Thiotepa, not a curated reading list.
Shares IELSG32 second randomisation: whole-brain radiotherapy or autologous stem cell transplant as consolidation in primary CNS lymphoma, MATRix/IELSG43: high-dose chemotherapy and autologous stem cell transplant versus non-myeloablative consolidation in primary CNS lymphoma, IELSG32, MATRix/IELSG43.
Shares IELSG32, MATRix/IELSG43, Stem cell transplant in lymphoma: what it is still for, Primary CNS lymphoma.
Shares High-Risk Neuroblastoma Study 2 of SIOP-Europa-Neuroblastoma (SIOPEN), Stem cell transplant in lymphoma: what it is still for, High-risk neuroblastoma, Primary CNS lymphoma.
Shares ALL-SCT BFM International- HSCT in Children and Adolescents With ALL, Allogeneic stem cell transplantation, Cytotoxic chemotherapy.
Shares High-Risk Neuroblastoma Study 2 of SIOP-Europa-Neuroblastoma (SIOPEN), Stem cell transplant in lymphoma: what it is still for, High-risk neuroblastoma, Autologous stem cell transplant (high-dose therapy).
Shares Central nervous system germ cell tumours (germinoma and non-germinomatous), Group 3 and group 4 medulloblastoma (non-WNT/non-SHH), SHH-activated medulloblastoma.
Shares IELSG32 first randomisation: the MATRix regimen (methotrexate, cytarabine, thiotepa, rituximab) in primary CNS lymphoma, IELSG32, MATRix/IELSG43, Stem cell transplant in lymphoma: what it is still for.
Shares ACNS0122, Central nervous system germ cell tumours (germinoma and non-germinomatous).