Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1140680 (ovarian cancer)
 28,141 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-two patients were treated for bulky stage IIIb and/or stage IV ovarian cancer with methotrexate (MTX), triethylenethiophosphoramide (thio-TEPA), or combination of the two. Two cycles of MTX 3 weeks apart failed to result in any important tumor shrinkage in 9 to 10 patients; thio-TEPA, in contrast, produced a rapid objective tumor regression in 8 of 12 patients. In addition, 4 of 8 patients who had not responded to MTX showed greater than 50% objective tumor regression during the first 4 weeks after crossover to thio-TEPA. The kinetics or drug penetration factor of the cell cycle-specific agent (MTX) in two oral cycles was of no clinical value alone in bulky ovarian cancer.
 ...
PMID:Comparison of regression induction with triethylenethiophosphoramide or methotrexate in bulky stage IIIb ovarian carcinoma. 82 79

The serum pharmacokinetics of unchanged thio-TEPA and the active metabolite TEPA and the urinary excretion of thio-TEPA, TEPA and total alkylating activity were studied after a single i.v. bolus injection of thio-TEPA in six ovarian cancer patients. TEPA was present in serum as of 5 min after drug administration, and its concentration rapidly reached a plateau in the range of 50-100 ng/ml. After about 3 h the serum concentration of TEPA exceeded that of thio-TEPA, and in five of the six patients the metabolite persisted longer than the parent drug in serum. AUCs of thio-TEPA and TEPA were 822 +/- 83 and 1,084 +/- 234 ng h/ml, respectively. The great interindividual variation encountered in the serum pharmacokinetics of TEPA may be of clinical importance and represents a further indication that pharmacokinetically guided dosing of thio-TEPA could be valuable. Urinary recoveries of both thio-TEPA and TEPA were low, together constituting less than 2% of the delivered dose. A substantial gap existed between this and the total urinary alkylating activity, which averaged 13% of the dose in terms of thio-TEPA equivalents. This gap strongly indicates the presence of other unknown metabolites.
 ...
PMID:Long-term pharmacokinetics of thio-TEPA, TEPA and total alkylating activity following i.v. bolus administration of thio-TEPA in ovarian cancer patients. 168 14

A total of 13 patients with ovarian cancer were studied during the initial two courses of i.v. thio-TEPA treatment they underwent after primary surgery. Following an increase in the dose from 60 to 80 mg for the second course, no sign of saturation of thio-TEPA elimination processes or of formation of the metabolite TEPA occurred, indicating dose-independent pharmacokinetics. Myelosuppression after courses was registered by serial measurements of platelets and leukocytes. The time to platelet nadir was quite uniformly 3 weeks and tended to be longer than that of leukocytes, which averaged 2 weeks but showed greater interindividual variation. Linear regression analyses of pharmacokinetic parameters versus myelosuppression revealed statistically significant correlations between thio-TEPA pharmacokinetics and the percentage of reductions in leukocytes and platelets at their mean nadirs. In contrast, no such correlation could be demonstrated for TEPA despite its greater exposure to the body in terms of AUC. We advocate further investigation of this pharmacokinetic-pharmacodynamic relationship so as to establish individualized dosing of thio-TEPA.
 ...
PMID:Pharmacokinetics of thio-TEPA and TEPA in the conventional dose-range and its correlation to myelosuppressive effects. 170 89

On the basis of a Phase I reevaluation of thio-TEPA in which 3 of 9 patients with ovarian carcinoma responded, we instituted a Phase II study at high doses. Fourteen patients with a histologic diagnosis of epithelial carcinoma of the ovary, who had received at least one prior cisplatin-based regimen, were entered. Thio-TEPA was initially administered intravenously at a dose of 65 mg/m2 every 4 weeks, but was reduced to 50 mg/m2 after severe myelotoxicity developed in the first 5 patients. In 4 patients stable disease lasted 3, 4, 5, and 9 months; 10 patients progressed. There were no objective responses. At this dose and schedule, thio-TEPA has a response rate less than 20% in ovarian cancer patients previously treated with cisplatin.
 ...
PMID:Phase II trial of thio-TEPA in relapsed and refractory ovarian carcinoma. 175 94

Thirty-five patients with advanced gynecologic malignancies were entered into a phase I study evaluating thio-TEPA in combination with cisplatin (50 mg/m2) intravenously every 4 weeks. Thirty-four patients were evaluable for toxicity and response, and one was evaluable for toxicity only. Median age was 53 years (range 28-72), and performance status less than or equal to 2. Prior treatment included chemotherapy in 21 patients, radiation in 15, hormonal therapy in 3, and immunotherapy in 1. Thio-TEPA was given to three or more patients at each of the following dose levels: 15, 20, 25, 30, 40, 50, and 60 mg/m2. Thio-TEPA's primary toxicity was myelosuppression; at 50 mg/m2, grade 3 or 4 granulocytopenia occurred in 13 of 17 cycles, and grade 3 or 4 thrombocytopenia occurred in 8 of 17 cycles. The maximum tolerated dose (MTD) of thio-TEPA was 40 mg/m2; in 35 cycles at this dose, grade 3 or 4 granulocytopenia occurred in 19, and grade 3 or 4 thrombocytopenia occurred in 10 cycles; median granulocyte nadir was 1100 (range 110 to 3600) and median platelet nadir was 90,000 (range 10,000 to 289,000). Fifteen patients received three or more cycles at one dose level; cumulative myelosuppression was observed in 11. Two cases of partial alopecia occurred at 40 and 60 mg/m2 thio-TEPA. Responses were as follows: complete response, 5; partial response, 7; stable disease, 14; progressive disease, 8. In 16 patients with ovarian cancer (15 of whom had previously received cisplatin), there were 4 complete responses and 5 partial responses (overall response rate of 56%). The thio-TEPA dose recommended in combination with cisplatin (50 mg/m2) in phase II trials is 40 mg/m2. Cumulative hematologic toxicity may occur with this regimen.
 ...
PMID:Phase I evaluation of thio-TEPA in combination with cisplatin for advanced gynecologic malignancies. 212 28

Drug resistant phenomenon to antitumor agents remains a major problem in cancer chemotherapy. In this study, we attempted to overcome drug resistance using high-dose chemotherapy with autologous bone marrow transplantation (ABMT). The main regimen consisted of Cyclophosphamide 60 mg/kg/day and thio-TEPA 6 mg/kg/day which were infused for 3 consecutive days. Three patients with malignant lymphoma, four with breast cancer, two with gastric cancer and one with ovarian cancer. All of whom were refractory to conventional chemotherapies were treated. The overall response rate was 70%. Severe bone marrow suppression, mucositis and diarrhea were observed in all patients, but these were not life-threatening and clinically manageable. Furthermore, the administration of granulocyte colony stimulating factor (G-CSF) has significantly (p less than 0.05) shortened the duration of leukopenia, and has been judged to be useful for reducing severe infections and for shortening the period stayed in clean room. Our results indicates that high-dose chemotherapy with ABMT is an effective method for overcoming drug resistance.
 ...
PMID:[A study to overcome drug resistance using high-dose chemotherapy with autologous bone marrow transplantation]. 247 62

Thio-TEPA pharmacokinetics were studied at doses of 20 mg and 30 mg in six patients treated for ovarian cancer. Considerable interindividual variation was encountered in its pharmacokinetics, which were dose-independent within the dose range studied and similar to those reported at far higher doses. Interindividual dosing of thio-TEPA based on an initial AUC estimation is suggested.
 ...
PMID:Pharmacokinetics of thio-TEPA at two different doses. 313 16