Revisiting intrathecal thiotepa: Efficacy and safety in secondary CNS malignancies

Treating metastatic malignancies to the central nervous system (CNS) is challenging because many drugs cannot cross the blood-brain-barrier (BBB). Direct intrathecal (IT) drug administration into the cerebrospinal fluid (CSF) is a strategy to overcome this problem. Thiotepa has effective CNS penetra...

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Published in:Medical oncology (Northwood, London, England) London, England), 2024-06, Vol.41 (7), p.177, Article 177
Main Authors: Jamison, Trevor, Haque, Emaan, Muhsen, Ibrahim N., Samarkandi, Hadeel, Fakih, Riad El, Aljurf, Mahmoud
Format: Article
Language:English
Subjects:
Antineoplastic Agents, Alkylating - administration & dosage
Antineoplastic Agents, Alkylating - adverse effects
Brain research
Case reports
Cellular biology
Central Nervous System Neoplasms - drug therapy
Central Nervous System Neoplasms - secondary
Cerebrospinal fluid
Chemotherapy
Disease prevention
Drug dosages
Hematologic Neoplasms - drug therapy
Hematology
Humans
Injections, Spinal
Internal Medicine
Leukemia
Lymphoma
Medicine
Medicine & Public Health
Meningeal Neoplasms - drug therapy
Meningeal Neoplasms - secondary
Metastasis
Multiple myeloma
Nervous system
Oncology
Pathology
Patients
Pediatrics
Remission (Medicine)
Review Article
Thiotepa - administration & dosage
Thiotepa - adverse effects
Toxicity
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Summary:Treating metastatic malignancies to the central nervous system (CNS) is challenging because many drugs cannot cross the blood-brain-barrier (BBB). Direct intrathecal (IT) drug administration into the cerebrospinal fluid (CSF) is a strategy to overcome this problem. Thiotepa has effective CNS penetration but its popularity has waned over the last two decades due to concerns about its efficacy and potential systemic toxicity. This review evaluates the available evidence for the use of IT thiotepa in hematologic malignancies and non-CNS solid tumors with leptomeningeal disease metastases (LMD). Our search shows that IT thiotepa is a reasonable alternative in hematologic malignancies and LMD due to solid organ malignancies. This suggests a potential role of IT thiotepa in second-or third-line treatment or a substitute role in cases of drug-shortages and adverse effects with other agents. Future research should focus on rigorous comparative trials to establish its definitive role in the evolving landscape of CNS-directed chemotherapy.
ISSN:1559-131X
1357-0560
1559-131X
DOI:10.1007/s12032-024-02401-w