Thiotepa
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
Thiotepa: From Lymphoma and Breast/Ovarian Cancer to Adult Germ Cell Tumor
One-Sentence Summary
Thiotepa is an alkylating chemotherapy drug, originally used for lymphomas (including Hodgkin and non-Hodgkin lymphoma), breast cancer and ovarian cancer. The TxGNN model predicts it may be effective for adult germ cell tumor, with 14 clinical trials and 20 publications compiled for this direction. Most of this evidence comes from single-arm Phase 2 studies of high-dose regimens with stem cell rescue.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Lymphomas (Hodgkin and non-Hodgkin, mantle cell), B-cell neoplasm, breast cancer, ovarian cancer (the Singapore licence records contain no approved-indication text) |
| Predicted New Indication | Adult germ cell tumor |
| TxGNN Prediction Score | 98.51% |
| Evidence Level | L2 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 5 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Thiotepa is known to be a polyfunctional alkylating agent that cross-links DNA. At high doses it is myeloablative, which is why it is used in conditioning regimens before autologous stem cell transplant.
Germ cell tumors are highly chemosensitive, and even relapsed or poor-risk patients can sometimes be salvaged with high-dose chemotherapy and stem cell rescue. High-dose regimens containing thiotepa (often with carboplatin and etoposide) take advantage of the dose-response relationship of alkylator/platinum cytotoxicity. This is consistent with thiotepa's established use in other blood and solid cancers.
The evidence is mainly from single-arm Phase 2 studies and cohort reports. No Phase 3 RCT directly supporting thiotepa in this indication was found in the data compiled for this report.
Clinical Trial Evidence
Fourteen trials were identified. The ten most relevant are listed below.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00432094 | Phase 2 | Completed | 23 | Autologous peripheral blood stem cell transplant specifically for germ cell tumors; small single-arm study supporting feasibility |
| NCT00003173 | Phase 2 | Completed | 36 | High-dose thiotepa with autologous stem cell rescue in malignancies refractory to conventional chemotherapy; germ cell results cannot be separated out |
| NCT00007982 | Phase 2 | Completed | 30 | Intensive chemotherapy (BET) with stem cell transplant for selected malignant CNS tumors |
| NCT00025558 | Phase 1 | Completed | N/A | Temozolomide dose escalation with thiotepa and carboplatin plus autologous stem cell rescue in malignant brain tumors; combination safety data |
| NCT00002619 | Phase 2 | Completed | 60 | Intensive chemotherapy with autologous stem cell reconstitution in glioblastoma or brainstem tumors |
| NCT00003101 | Phase 2 | Completed | 60 | Intensive chemotherapy and autotransplantation in newly diagnosed anaplastic oligodendroglioma |
| NCT04684368 | Phase 2 | Recruiting | 160 | Chemotherapy followed by response-based irradiation in localized non-germinomatous CNS germ cell tumor; thiotepa's role unconfirmed |
| NCT00060255 | Phase 2 | Completed | 451 | Autologous transplant with eight high-dose regimens for blood cancers and selected solid tumors; indirect |
| NCT00536601 | N/A | Completed | 174 | Autologous transplant for blood cancers and selected solid tumors; heterogeneous and indirect |
| NCT04530487 | Phase 2 | Terminated | 1 | Allogeneic stem cell transplant in pediatric and young adult high-risk solid tumors; terminated early, not informative |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 15143087 | 2004 | Clinical study | J Clin Oncol | Thiotepa-based high-dose chemotherapy with autologous stem cell rescue in recurrent or progressive CNS germ cell tumors |
| 15803005 | 2005 | Cohort (Phase I/II) | Am J Clin Oncol | High-dose etoposide, thiotepa and carboplatin with stem cell rescue in relapsed or refractory germ cell cancer |
| 8622061 | 1996 | Cohort | J Clin Oncol | Feasibility of multiple courses of high-dose cyclophosphamide, thiotepa and carboplatin for breast or germ cell cancer |
| 28463397 | 2017 | Retrospective cohort | Int J Cancer | Outcomes in relapsed intracranial germ cell tumors, including the value of high-dose chemotherapy with stem cell rescue |
| 11583199 | 2001 | Cohort | Ann Oncol | Amifostine protection against toxicity from high-dose carboplatin, etoposide and thiotepa in germ cell tumor |
| 12483368 | 2002 | Clinical study | Ann Hematol | Amifostine and immune reconstitution after high-dose carboplatin, etoposide and thiotepa in 40 germ cell tumor patients |
| 31454045 | 2019 | RCT | JAMA | Tandem vs single autologous transplant in high-risk neuroblastoma; indirect (different disease) |
| 11996467 | 2002 | Pharmacokinetic study | Ann Oncol | Exposure-toxicity relationship of high-dose cyclophosphamide, thiotepa and carboplatin |
| 11157041 | 2001 | Review | J Clin Oncol | Dose-intensive/myeloablative therapy in metastatic Ewing sarcoma/PNET; indirect |
| 15701281 | 2005 | Cohort | Neuro-oncology | Sequential chemotherapy and high-dose thiotepa for childhood high-grade glioma; indirect |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN16553P | TEPADINA 15 mg/vial | Lyophilised powder for injection | Not recorded |
| SIN16552P | TEPADINA 100 mg/vial | Lyophilised powder for injection | Not recorded |
| SIN17095P | TEPADINA 400 mg | Powder for solution for infusion | Not recorded |
| SIN17028P | THIOTEPA RIEMSER 100 mg/vial | Lyophilised powder for injection | Not recorded |
| SIN17027P | THIOTEPA RIEMSER 15 mg/vial | Lyophilised powder for injection | Not recorded |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (alkylating agent) |
| Myelosuppression Risk | High (myeloablative at high doses; stem cell rescue is required) |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | CBC with differential, platelets, liver and renal function |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Safety Considerations
- Disease-level cautions (from the knowledge graph, not label text): kidney disease, liver disease, gallbladder disease, thrombocytopenia, blood coagulation disease, anemia, macrocytic anemia, leukopenia, pyoureter.
- Drug Interactions: 100 interactions were found in total. The main ones rated Major are deferiprone and samarium (153Sm) lexidronam. Moderate ones include bupropion, palifermin, strontium chloride Sr-89 and fostamatinib. Most others (such as morphine, omeprazole, prednisone, dexamethasone, heparin and warfarin) have no severity rating.
Package insert warnings and contraindications were not available in the data compiled for this report. Please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Thiotepa is already marketed in Singapore as an injectable. Several Phase 2 studies and cohort reports support high-dose thiotepa-containing regimens with stem cell rescue in germ cell tumors, including relapsed disease. However, the studies are small and single-arm, and no Phase 3 RCT is available. The other predicted subtypes (testicular yolk sac tumor histologic patterns) have no clinical evidence and should stay on Hold. Childhood ovarian yolk sac tumor is a research question only, supported by one small non-specific Phase 2 study.
To proceed, the following is needed:
- Package insert warnings and contraindications (a blocking gap for safety screening)
- Mechanism of action data
- Approved-indication text for the Singapore licences, to confirm the original indications
- Germ cell tumor-specific results from the multi-disease trials
- A safety and monitoring plan for high-dose use (myelosuppression, organ function, interaction screening)
- Confirmation of the thiotepa regimen and dose in the ongoing CNS germ cell tumor trial (NCT04684368)
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.