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At least 19 recordsLinked to original sources
PubMed1979

Acute metabolic effects of nitrogen mustard and thiotepa on rabbit articular cartilage and synovium.

Metabolic alterations in immature rabbit joint tissue were examined following in vitro and in vivo exposure to the alkylating agents Thiotepa and nitrogen mustard. Brief exposure in vitro to either agent resulted in marked suppression of incorporation of radiolabeled precursors of protein, RNA, and glycosaminoglycan synthesis in articular cartilage, which was partially reversible after Thiotepa exposure. In vivo, nitrogen mustard has little effect on synovium and transient inhibitory effects on cartilage vital processes, whereas Thiotepa caused a prolonged inhibition of synovial metabolism with little effect on cartilage. Autoradiographic localization of labeled agents indicated that synovial tissue and cartilage were readily penetrated by nitrogen mustard, but only a few synovial lining cells and superficial chondrocytes were labeled with 35S-Thiotepa. Furthermore, trypsin significantly reduced labeling of cartilage with 14C-nitrogen mustard. These data suggest that alkylating agents differentially affect metabolic processes in joint tissues in vivo and that with Thiotepa, this interference occurs primarily in the synovium. The degree of interference is apparently dependent upon the time of exposure to the agents and the relative DNA-RNA synthetic activity of the joint tissue.

Animals↗
PubMed1978

Management of pterygia: should thiotepa be used?

Pterygium, a common source of morbidity throughout the world, may appear to be an innocuous, easily excised lesion, yet it plagues the ophthalmologist by its high rate of recurrence, ranging from 20% to 30% after simple excision. Beta irradiation has been used by ophthalmic surgeons for many years. Another method of stemming the high percentage of pterygium recurrence is through local application of thiotepa, a radiomimetic drug that inhibits rapidly proliferating cells. The following report is a review of the literature from 1960 to 1977 on the role of thiotepa in treatment of pterygium, with emphasis on the complications of thiotepa administration. The recurrence rate after topical postoperative use of thiotepa ranges from 0 to 8%, with disturbing variance in results, depending on each investigator's definition of "recurrence", the length of follow-up, the type of pterygium, and the number of patients. The main reported complication from thiotepa's use has been depigmentation of skin around several patients' eyes, sometimes precipitated by exposure to the sun's rays.

Animals↗
PubMed1976

Single dose intravesical thiotepa as an adjuvant to cystodiathermy in the treatment of transitional cell bladder carcinoma.

Tumour cell implantation may be a factor in the aetiology of recurrent well-differentiated superficial bladder tumours. A prospective trial is reported in which single dose intravesical thiotepa was administered to a group of randomly selected patients immediately after cystodiathermy. A control group of patients was treated by cystodiathermy alone and tumour recurrence in the 2 groups was compared. Significantly fewer patients in the thiotepa-treated group developed recurrent tumour and there was also a significantly reduced incidence of pure vault recurrence in this group. The beneficial effects of adjuvant thiotepa were apparent after 1 treatment. In this series of patients no benefit resulted from the continued use of adjuvant thiotepa once a patient developed a recurrent tumor.

Carcinoma, Transitional Cell↗
PubMed1977

Comparisons of placebo, pyridoxine, and topical thiotepa in preventing recurrence of stage I bladder cancer.

Animal studies have shown that metabolites of tryptophan can cause bladder cancer, and human observations reveal an appreciable incidence of abnormalities of tryptophan metabolism in patients with bladder cancer. It has been suggested that pyridoxine (vitamin B6) may correct this abnormality and prevent recurrences of superficial bladder cancers. Intravesical instillation of thiotepa has been used for more than fifteen years in the treatment of superficial bladder cancer, but no controlled trials have been done. We report here a prospective clinical trial of 121 patients with Stage I bladder cancer randomized to placebo, pyridoxine, or intravesical thiotepa. The percentages of patients with recurrences over the period of study were 60.4, 46.9, and 47.4 for the three groups, respectively, and did not differ significantly. However, if patients having recurrences during the first ten months or followed up less than ten months were excluded, pyridoxine was significantly better than placebo (P = 0.03). Thiotepa significantly reduced the recurrence rate compared with placebo (P = 0.016) or pyridoxine (P = 0.015). These results suggest that a new trial of pyridoxine should be undertaken in which the tryptophan metabolites are measured and that further study of intravesical instillation of chemotherapeutic agents is warranted.

Administration, Oral↗
PubMedDate not supplied

Effects of thiotepa on the productivity of male Aedes aegypti.

The effects of various concentrations of thiotepa, a chemomutagen, on the genetic fitness of Aedes aegypti males was studied. Oral treatments of 0.025 percent, 0.050 percent and 0.075 percent thiotepa induced sexual sterility in the male mosquitoes. Analyses of total F2 productivity indicate that the mean number of progeny was significantly decreased with exposure to 0.001 percent of the chemomutagen. At 0.001 percent thiotepa only a mean of 198.04 F2 progeny per culture were produced; by comparison the control group gave 315.33.

Aedes↗
PubMed1977

The role of intravesical thiotepa in the management of superficial bladder cancer. National Bladder Cancer Collaborative Group A.

This report describes and presents some preliminary results from a prospective clinical investigation to determine the ablative effect of thiotepa (N,N',N''-triethylene phosphoramide) on superficial low-stage bladder cancer and the effectiveness of this agent in the prevention of recurrent or new tumors. In the small group of cases studied thus far, therapeutic thiotepa has destroyed superficial cancers in 33 to 36% of the cases, about the same results as those reported by others. It is too early in the study to assess the benefit from the prophylactic use of thiotepa.

Clinical Trials as Topic↗
PubMed1976

Permeability of the bladder mucosa to thiotepa, adriamycin, and daunomycin in men and rabbits.

The permeability of the bladder mucosa to thiotepa and to the anthraquinonic antibiotics, adriamycin and daunomycin, was investigated both in humans and in experimental animals. Instillations in rabbits were performed either in intact males or in animals with ligated ureters. Absorption of thiotepa was significantly higher than that of the antibiotics both in men and in rabbits. Furthermore, a qualitative difference was observed in rabbits in relation to time and with regard to fixation to vesical tissues. In man, absorption was highest after transurethral surgery. It was also increased in cases with extensive anaplastic tumours or in the presence of acute inflammatory reactions.

Animals↗
PubMedDate not supplied

[Thiotepa in the treatment of central nervous system leukemia in children].

The authors report beneficial effects of thiotepa on leukaemic involvement of the central nervous system. The drug was given to 4 children with central nervous system leukaemia refractory to methotrexate and cytarabine. Intrathecal thiotepa caused regression of changes in the cerebrospinal fluid and in the neurological status of these children. No side effects were observed during this treatment.

Age Factors↗
PubMedDate not supplied

[WR, a new strain of mice, highly sensitive to the cytogenetic effect of thiotepa].

Mice of the WR strain (genotype -aa, +WY) were selected for the appearance of black spots with normal pigmentation, presumably due to genetic recombination in the W gene region. The frequency of heterozigotes +WY with black spots was 25% in the 11th generation. The cytogenetic effect of thioTEPA (dose 5 mg/kg) was investigated in bone marrow cells of C57BL/10 NZW, 101/H and 129/Re mice. Mice of the WR strain were most sensitive to thioTEPA. It is suggested that the WR mice may be used as a sensitive object for the genetical screening of chemical compounds.

Animals↗
PubMed1976

Toxicity, antitumor activity, and pharmacokinetics of spin-labeled thioTEPA analogs.

Two spin-labeled analogs of thioTEPA, containing an iminoxyl radical, have been shown to have significant antitumor activity in several experimental tumor systems, combined with a marked decrease in toxicity compared with the parent compound, thioTEPA. Walker 256 carcinosarcoma, Guérin carcinoma, and Schweitz erythromyelosis showed complete regression using one of these analogs. Pharmacokinetic studies have shown that these compounds possess particular affinity towards tumor tissue.

Adenocarcinoma↗
PubMed1978

Vinblastine, adriamycin, thiotepa, and halotestin (VATH): therapy for advanced breast cancer refractory to prior chemotherapy.

Nineteen postmenopausal patients with metastatic breast cancer refractory to conventional combination chemotherapy were treated with monthly cycles with the combinations of vinblastine, adriamycin, thiotepa and halotestin. Ten patients (52%) responded with a greater than 50% regression of measurable tumor. The median duration of response was 11.5 months, with 5/10 patients still responding at a mean follow-up of 10 months. Only 2/10 responders have died with a mean follow-up of 13.8 months. In contrast, 8/9 nonresponders have died (median survival 6.0 months). Response to therapy was neither influenced by site of disease, time interval from diagnosis to primary chemotherapy nor duration of response to primary chemotherapy. No patient was hospitalized because of drug induced toxicity. This combination of drugs is a tolerable effective regimen for patients relapsing after adjuvant chemotherapy or after primary combination chemotherapy for grossly metastatic disease.

Adult↗
PubMed1979

Thiotepa-induced leukoderma.

Periorbital depigmentation developed in a black man approximately six months after the application of an ophthalmic solution containing thiotepa. The drug was used postoperatively to prevent revascularization after removal of a pterygium. By light and electron microscopy, melanocytes were apparently absent in the depigmented area. The list of medications and chemicals that can cause cutaneous depigmentation is growing. An appropriate history may be of considerable value in the evaluation of vitiligo-like conditions.

Black People↗
PubMed1979

The apparent decrease in thiotepa-induced chromosome aberrations in human lymphocytes caused by an effect of WR2721 on the cell cycle as found by the definitively determined division method.

Antimutagenic radioprotective compounds have been reported to decrease the yield of chemically induced chromosome aberrations even when administered long before the chemical mutagen thio-TEPA. Because thio-TEPA can induce aberrations in all parts of the cell cycle, it seemed likely that the apparent decrease in aberrations was the result of an effect of the antimutagen on the progression of cells through the cell cycle so that cells treated in the more sensitive stage would be scored. To test this possibility human lymphocytes were treated with the protective compound WR2721 and then thio-TEPA. The cells were grown in the presence of 5-bromodeoxyuridine, which allows the definitive determination of metaphases from cells that divided once, twice, or three times after treatment. The yield of aberrations observed in first division cells was the same whether or not the protector was present. A decrease in aberration yields appeared only in rapidly cycling cells that were in the second division at the time of fixation. Labeling experiments showed that in this rapidly dividing population fewer of the metaphase cells had been in G2 when thio-TEPA was added. The results indicate that part of the decrease in aberration yields obtained by treatment with an antimutagen several hours before the addition of a mutagen is an artifact of cell selection.

Amifostine↗