Disease relevance of thiotepa

• Twenty-nine patients with bladder carcinoma treated with intravesical thiotepa administration were reviewed to assess hematologic toxicity [1].
• Forty patients with refractory solid tumors or non-Hodgkin's lymphoma were treated with high-dose cyclophosphamide, thiotepa, and carmustine (BCNU), followed by autologous stem cell rescue, in a phase I dose escalation study [2].
• Twenty-seven patients with essential thrombocythemia were treated with combination chemotherapy consisting of weekly intravenous thiotepa (until the platelet count fell below 1,000 X 10(3)/cu mm) and daily chlorambucil (until a sustained remission, platelet count less than 400 X 10(3)/cu mm) [3].
• Glutathione-dependent biotransformation of the alkylating drug thiotepa and transport of its metabolite monoglutathionylthiotepa in human MCF-7 breast cancer cells [4].
• CONCLUSION: The combination of high-dose thiotepa and etoposide has activity against a variety of recurrent childhood brain tumors [5].

Psychiatry related information on thiotepa

• Twenty-four patients with transitional cell carcinoma of the bladder, who had failed thiotepa therapy, were subjected to immunotherapy with intravesical bacillus Calmette-Guérin (BCG) by a modification of the Morales protocol [6].
• Veno-occlusive disease of the liver after busulfan, melphalan, and thiotepa conditioning therapy: incidence, risk factors, and outcome [7].

High impact information on thiotepa

• METHODS: Forty-three patients with high-risk acute leukemia who were scheduled for transplantation received total-body irradiation, thiotepa, fludarabine, and antithymocyte globulin [8].
• When alkylating agents and toxin conjugates were used in combination, the addition of the immunotoxins to cisplatin, or to cisplatin and thiotepa, produced synergistic cytotoxic activity against the OVCA 432 and OVCAR III cell lines [9].
• Continuous infusion cyclophosphamide and thiotepa is an active core regimen for the further design of high-dose combination chemotherapy regimens [10].
• Cyclophosphamide and thiotepa with autologous bone marrow transplantation in patients with solid tumors [10].
• RIC regimens included fludarabine/total body irradiation 200 cGy (n = 5) or 450 cGy (n = 1), fludarabine/melphalan (n = 7), thiotepa/cyclophosphamide (n = 7), and thiotepa/fludarabine (n = 1) [11].

Chemical compound and disease context of thiotepa

• Although there are substantial toxicities associated with this regimen, high-dose thiotepa and cyclophosphamide produce high response rates in patients with disseminated cancer [12].
• High-dose carboplatin, thiotepa, and etoposide with autologous stem-cell rescue for patients with recurrent medulloblastoma. Children's Cancer Group [13].
• In terms of survival or toxicity, an advantage for melphalan or thiotepa was not evident [14].
• PATIENTS AND METHODS: In a 54-month period, 373 patients with hematologic malignancies underwent allogeneic or autologous bone marrow transplantation (BMT) or blood stem-cell transplantation using high-dose thiotepa, busulfan, and cyclophosphamide (TBC) as the preparative regimen [15].
• Randomized prospective comparison of intraventricular methotrexate and thiotepa in patients with previously untreated neoplastic meningitis. Eastern Cooperative Oncology Group [16].

Biological context of thiotepa

• Pharmacokinetics of intraventricular and intravenous N,N',N''-triethylenethiophosphoramide (thiotepa) in rhesus monkeys and humans [17].
• The maximum tolerated dose (MTD) of thiotepa was 700 mg/m2 or 6 mg/kg for three doses [12].
• The AUC of thiotepa was approximately twice, and the clearance about one-half, of the values obtained in a previous study of single agent thiotepa [18].
• Tumor cell lethality was increased up to 10-fold by either caffeine or pentoxifylline (1 mM) present during the first cell cycle (16-24 h) after exposure to nitrogen mustard (HN2) or thiotepa [19].
• Tumor cell survival experiments with the EMT6 mouse mammary carcinoma system revealed that a 3.6-fold increase in thiotepa cytotoxicity was obtained by prior administration of the liver inducer Aroclor 1254 to the tumor-bearing animals, 5 days before drug treatment [20].

Anatomical context of thiotepa

• The day +28 T cells were exclusively of donor origin in 14 of 17 patients who received TBI plus thiotepa plus Cy, but were mixed chimeric in 10 of 12 patients who received other conditioning regimens (P < .001) [21].
• Pharmacokinetic studies performed in nine patients revealed that thiotepa was rapidly lost from the peritoneal cavity in a biexponential fashion with a mean t1/2 alpha of 0.26 +/- 0.08 hour and a mean t1/2 beta of 2.13 +/- 0.52 hour [22].
• Phase I and pharmacokinetic evaluation of thiotepa in the cerebrospinal fluid and plasma of pediatric patients: evidence for dose-dependent plasma clearance of thiotepa [23].
• Thiotepa-based high-dose chemotherapy with autologous stem-cell rescue in patients with recurrent or progressive CNS germ cell tumors [24].
• METHODS: Women with newly diagnosed disease received four 2-week cycles of doxorubicin 90 mg/m2 with granulocyte colony-stimulating factor (G-CSF), followed by cyclophosphamide 6,000 mg/m2, thiotepa 500 mg/m2, and carboplatin 800 mg/m2 (CTCb) with marrow and peripheral-blood progenitor cell (PBPC) support [25].

Associations of thiotepa with other chemical compounds

• These PBPCs were reinfused as the sole source of hematopoietic support after high doses of cyclophosphamide, thiotepa, and carboplatin [26].
• Other univariable risk factors included older age (P <.01), busulfan/melphalan/thiotepa conditioning (P <.01), interleukin-2 (P =.02), HLA-A26 (P =.03), and more recent transplantation year (P <.01) [27].
• The in vitro cytotoxicities of the four drugs most frequently used for intravesical chemotherapy (Adriamycin, epodyl, mitomycin C, Thiotepa) and epirubicin were compared using monolayers and multicellular tumor spheroids of the human bladder cancer cell line, MGH-U1 [28].
• Median survival for patients receiving methotrexate was 15.9 weeks and 14.1 weeks for patients treated with thiotepa [16].
• We tested the effect of LSF (100 mg/kg i.p., b.i.d.) on multilineage regeneration after high-dose 5-FU or thiotepa treatment in BALB/c mice [29].

Gene context of thiotepa

• Experiments with thiotepa and ketoconazole suggested inhibition of microsomal CYP2B6 and CYP3A4 activity, whereas studies with fluvoxamine (a substrate of CYP2C19) were inconclusive due to lack of specificity [30].
• In this study, we used XL1-Blue MRF strain, transformed with phagemid expression vectors carrying cDNAs of three GSTP1 alleles, to investigate the cytoprotective abilities of the different GSTP1 alleles against four clinically active anticancer agents, namely, carboplatin, cisplatin, thiotepa, and 4-hydroperoxyifosfamide [31].
• PATIENTS AND METHODS: We performed a trial of stem-cell mobilization with IL-2 and G-CSF in advanced breast cancer patients receiving high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin and stem cells followed by IL-2 [32].
• Hprt mutant frequency and molecular analysis of Hprt mutations in Fischer 344 rats treated with thiotepa [33].
• There is a potential for CYP-mediated drug interactions with thiotepa [34].

Analytical, diagnostic and therapeutic context of thiotepa

• These children received transplants as part of a prospective phase I/II study of thioTEPA (TT) and total body irradiation (TBI) with escalating doses of VP-16 [35].
• After treatment of the patient with total body irradiation and cyclophosphamide (n = 7) or etoposide, thiotepa, and cyclophosphamide (n = 1), PBSCs were infused immediately after collection and without modification [36].
• Intracavitary chemotherapy with thiotepa in malignant pericardial effusions: an active and well-tolerated regimen [37].
• We also showed that established tumor cell masses regressed following intravesical administration of the chemotherapeutic drug thiotepa [38].
• PATIENTS AND METHODS: Twenty-one patients with CNS GCTs who experienced relapse or progression despite having received initial chemotherapy and/or radiotherapy were treated with thiotepa-based HDC regimens followed by ASCR [24].

References