The purpose of this study was to determine the influence of folie acid or vitamin B-12 on the course of the IRC 741 rat leukemia treated with thioTEPA. On the first day im mediately following tumor implantation into Fischer rats individual series of these ani mals were given 6 mg/kg thioTEPA, in a single injection, or 1 mg/kg, every other day for six doses without and with simultaneous injectio...

PURPOSE Relationships between toxicity and pharmacokinetics have been shown for cyclophosphamide, thiotepa, and carboplatin (CTC) in high-dose chemotherapy. We prospectively evaluated whether variability in exposure to CTC and their activated metabolites can be decreased with pharmacokinetically guided dose administration and evaluated its clinical effect. EXPERIMENTAL DESIGN Patients receive...

Some inhibitory agents against CYP2B6 have been reported, but none of these has been extensively characterized or compared with others, as to the potency and selectivity of inhibition toward CYP2B6. The goal of this work was to find a selective and potent chemical in vitro inhibitor toward CYP2B6 using bupropion hydroxylation as a model reaction. At the initial screening of more than 30 substan...

Pentoxifylline potentiates the cytotoxicity of alkylating agents in preclinical models. In this study we sought to define the maximum tolerated dose (MTD) of N,N’,N”triethylenethiophosphoramide (thioTEPA) with pentoxifylline, and to estimate the antitumor response to this combination in previously treated breast cancer patients. Thirtyfive previously treated advanced breast cancer patients rece...

The biological properties of l,4-dimethyl-l,4-diphenyl-2-tetrazene (centrazene), a new anti-neoplastic compound which is not an alkylating agent, were described and compared with those of thioTEPA. Short-term studies demonstrated that both centrazene and thioTEPA inhibited the growth of 72j mammary adenocarcinoma growing in C3H mice. ThioTEPA produced concurrent bone marrow damage, and its effe...

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. Adriamycin and epirubicin were most cytotoxic against monolayer cultures, whereas mitomycin C killed more cells in spheroids. Epo...

A 19-year-old man with systemic sclerosis (SSc) was hospitalized for autologous peripheral blood stem cell transplantation (auto-PBSCT) due to progressive scleroderma and cardiac involvement despite conventional treatment. During the administration of cyclophosphamide (60 mg/kg/day for 2 days) for mobilization and collection of CD34+ selected peripheral blood stem cells, he developed congestive...

Modulation of DNA damage repair activity could lead to new approaches to reduce cytotoxic side effects of chemotherapy. N,N',N"-Triethylenethiophosphoramide (thioTEPA) induces the formation of amino-ethyl adducts of guanine, resulting in imidazole ring opening [formamidopyrimidine (Fapy)] and is associated with significant myelosuppression in dose-intensive therapies. In Escherichia coli, Fapy ...

Background: Infertility problem affect more than 15% of young couples in different societies. One of the known causes of ovulation disorder is chemotherapy in patients with cancer. This side effect may last from ten years up to the end of the life. Since anticancer drugs are mainly insert their effect through decreasing of cell proliferation, the aim of the present study is to investigate, anti...

Alkylating agents can be administered in high dosage to patients with ovarian cancer using autologous bone marrow support, but drug-resistant tumor cells can still persist. Immunotoxins provide reagents that might eliminate drug resistant cells. In the present study, concurrent treatment with alkylators and immunotoxins proved superior to treatment with each agent alone. Toxin immunoconjugates ...