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IARC Monographs on the Evaluation of... 1990
Review
Topics: Animals; Carcinogens; Female; Humans; Male; Molecular Structure; Pregnancy; Reproduction; Thiotepa
PubMed: 2127291
DOI: No ID Found -
Report on Carcinogens : Carcinogen... 2011
Topics: Animals; Antineoplastic Agents, Alkylating; Carcinogens; Chemosterilants; Female; Neoplasms; Thiotepa
PubMed: 21863106
DOI: No ID Found -
Journal of Pediatric Oncology Nursing :... Apr 1991
Topics: Humans; Neoplasms; Thiotepa
PubMed: 1904247
DOI: 10.1177/104345429100800242 -
Report on Carcinogens : Carcinogen... 2004
Topics: Animals; Antineoplastic Agents, Alkylating; Carcinogenicity Tests; Carcinogens; Cells, Cultured; Female; Government Regulation; Guidelines as Topic; Humans; Male; Mice; Models, Biological; Occupational Exposure; Primates; Rabbits; Rats; Thiotepa; United States
PubMed: 21089968
DOI: No ID Found -
Cancer Treatment Reviews Aug 2000N,N',N" -triethylenethiophosphoramide (thioTEPA) is a trifunctional alkylating agent with a broad spectrum of antitumour activity developed in the 1950s. The drug is now... (Review)
Review
N,N',N" -triethylenethiophosphoramide (thioTEPA) is a trifunctional alkylating agent with a broad spectrum of antitumour activity developed in the 1950s. The drug is now experiencing renewed interest as it appears to be one of the most effective anticancer drugs in high dose regimens. Despite many years of experience with thioTEPA, pharmacologic data are incomplete and controversy remains with respect to the dose-dependent pharmacokinetics of thioTEPA. In recent years greater insight has been obtained into the metabolism of thioTEPA, but there is still a gap between the total urinary excretion of thioTEPA and metabolites and the alkylating activity. In vivo and in vitro studies show that alkylation of DNA by thioTEPA can follow two pathways, but it remains unclear which pathway represents the precise mechanism of action. The currently available sensitive analytical methods for thioTEPA and its metabolites can be used to elucidate the many questions that still exist even so many years after its introduction. An overview is given of the chemistry, pharmacology, clinical use and toxicity of thioTEPA as well as its pharmacokinetics and analytical methods for thioTEPA and its metabolites.
Topics: Animals; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Biotransformation; Carboplatin; Chromatography, Gas; Chromatography, High Pressure Liquid; Cyclophosphamide; Humans; Magnetic Resonance Spectroscopy; Molecular Structure; Thiotepa
PubMed: 10913381
DOI: 10.1053/ctrv.2000.0170 -
Leukemia & Lymphoma Dec 2014Thiothepa is a cytostatic agent used in managing solid malignancies, and also as conditioning treatment before hematopoietic stem cell transplantation [HSCT]. This... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Thiothepa is a cytostatic agent used in managing solid malignancies, and also as conditioning treatment before hematopoietic stem cell transplantation [HSCT]. This systematic review summarizes evidence on its effectiveness and safety, in patients with central nervous system [CNS] lymphoma.
METHODS
We searched 3 databases for clinical studies. When feasible, we performed meta-analyses.
RESULTS
We identified 13 eligible studies, none of which with a priori controls. So data synthesis focused on the 226 patients who received thiotepa. Based on pooled estimates, 75.9% of thiotepa-treated patients achieved a complete remission (95% confidence interval [CI] = 67.5-82.8), and 61.7% had a progression-free survival for up to 125 months post-treatment (95% CI = 49.4-72.7). However, 25.5% relapsed, 24.6% experienced infection, and 13.2% experienced neurotoxicity.
DISCUSSION
Thiotepa-based conditioning followed by HSCT may be effective in most CNS lymphoma patients, with a manageable toxicity profile. But adequately powered randomized trials are needed to better evaluate and isolate the effects of thiotepa.
Topics: Central Nervous System Neoplasms; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma; Myeloablative Agonists; Neoplasm Recurrence, Local; Publication Bias; Thiotepa; Transplantation Conditioning; Treatment Outcome
PubMed: 24491026
DOI: 10.3109/10428194.2014.889825 -
Synapse (New York, N.Y.) Jun 2019Cancer survivorship has increased greatly as therapies have become more advanced and effective. Thus, we must now focus on improving the quality of life of patients...
Cancer survivorship has increased greatly as therapies have become more advanced and effective. Thus, we must now focus on improving the quality of life of patients after treatment. After chemotherapy, many patients experience chemotherapy-induced cognitive decline, indicating a need to investigate pathologies associated with this condition. In this study, we addressed cognitive impairment after thioTEPA treatment by assessing behavior and assaying cytokine production and the structure of dendrites in the hippocampus. Male mice were given three intraperitoneal injections of thioTEPA. Five weeks later, the mice underwent behavior testing, and brains were collected for Golgi staining and cytokine analysis. Behavior tests included y-maze and Morris water maze and licking behavioral task. Cytokines measured include: IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-10, IL-12p70, MCP-1, TNF-α, GMCSF, and RANTES. We observed decreased memory retention in behavioral tasks. Also, dendritic arborization and length were decreased after chemotherapy treatment. Finally, thioTEPA decreased cytokine production in animals treated with chemotherapy, compared to saline-treated controls. Here, we used a mouse model to correlate the decreases in dendritic complexity and inflammatory cytokine production with cognitive impairment after chemotherapy.
Topics: Animals; Antineoplastic Agents, Alkylating; Brain; Cognition; Cognitive Dysfunction; Cytokines; Injections, Intraperitoneal; Male; Maze Learning; Mice; Mice, Inbred C57BL; Movement; Thiotepa
PubMed: 30586195
DOI: 10.1002/syn.22085 -
Seminars in Oncology Feb 1990N,N',N''-triethylenethiophosphoramide (thiotepa) is a polyfunctional alkylating agent similar in structure to nitrogen mustard. Thiotepa (synthesized by American... (Review)
Review
N,N',N''-triethylenethiophosphoramide (thiotepa) is a polyfunctional alkylating agent similar in structure to nitrogen mustard. Thiotepa (synthesized by American Cyanamid Company, Wayne, NJ) underwent clinical trials in the 1960s that showed that it was active against a wide variety of tumors. At a standard dose level (10 to 30 mg/m2), the dose-limiting toxicity is myelosuppression; other toxicities are infrequent. Therefore, high-dose phase I evaluation was encouraged by these observations. Approximately 217 patients have been treated with single-agent high-dose thiotepa administered intravenously daily over 2 hours for 3 days followed by hematopoietic stem cell rescue to prevent prolonged myelotoxicity. The total doses administered ranged from 135 to 1,575 mg/m2. As anticipated, myelotoxicity was substantial, with 180 mg/m2 being the highest dose not requiring stem cell rescue to ensure hematopoietic recovery. Extramedullary toxicities consisted of stomatitis, dermatitis, hepatoxicity, and central nervous system (CNS) toxicity. CNS toxicity was dose-limiting; other toxicities were problematic, ie, dose-dependent but not truly dose-limiting. The maximal tolerated dose of thiotepa is 900 to 1,125 mg/m2, with the lower dose being the maximal dose for evaluation in combination chemotherapy. In high-dose phase I evaluation, the overall response rate was approximately 50% with responses seen in a wide variety of solid tumors, lymphomas, and pediatric tumors. High-dose thiotepa appears to be an alkylating agent with broad-spectrum antitumor efficacy, which should add to the cytoreductive regimens for both solid and hematopoietic tumors.
Topics: Bone Marrow Transplantation; Combined Modality Therapy; Drug Evaluation; Humans; Neoplasms; Thiotepa
PubMed: 2106165
DOI: No ID Found -
Journal of Neuro-oncology Sep 2015
Topics: Antineoplastic Agents, Alkylating; Female; Humans; Neoplasm Recurrence, Local; Ovarian Neoplasms; Thiotepa; United States; Urinary Bladder Neoplasms
PubMed: 26209975
DOI: 10.1007/s11060-015-1856-4 -
Clinical Obstetrics and Gynecology Jun 1968
Review
Topics: Bone Marrow Diseases; Female; Humans; Infections; Injections, Intravenous; Ovarian Neoplasms; Palliative Care; Thiotepa
PubMed: 4176467
DOI: No ID Found