Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0007138 (transitional cell carcinoma)
 3,949 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phase II studies of single-agent docetaxel (Taxotere) yielded promising results in advanced or metastatic transitional cell carcinoma (TCC) of the urothelium. Antitumor responses have been demonstrated in previously treated and chemotherapy-naive TCC patients, as well as in a subgroup of patients with renal impairment unable to receive traditional cisplatin-based regimens. Investigations of docetaxel-containing doublet and triplet drug combinations in the first-line setting have been pursued. When combined with cisplatin in previously untreated patients, response rates of 52% to 60% have been achieved, with median overall survival of 8 to 13.6 months. Triplet drug combinations of the docetaxel/platinum base have been investigated, when the addition of an anthracycline (doxorubicin or epirubicin [Ellence]) or of gemcitabine (Gemzar) has proven feasible, and has resulted in favorable efficacy findings. Non-platinum-containing regimens such as docetaxel/gemcitabine are also being studied. Randomizedphase III trials of a docetaxel-containing regimen in comparison with established regimens are ongoing, and additional studies are warranted to determine if overall long-term survival of TCCpatients can be improved.
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PMID:Docetaxel in the management of advanced or metastatic urothelial tract cancer. 1210 93

We demonstrated recently that chronic frequent administration of an adequate biological dose of the angiogenesis inhibitor TNP-470 (AGM-1470, O-chloracetyl-carbamoyl fumagillol) completely inhibits spontaneous lymph node metastasis but does not have a complete response on tumor growth of nonestablished or established human metastatic transitional cell carcinoma (TCC) 253J B-V growing orthotopically into athymic nude mice. Therefore, in this study, we evaluated whether docetaxel (Taxotere) enhances the therapeutic effect of TNP-470, especially on tumor growth. Docetaxel enhanced in vitro antiproliferation but not basic fibroblast growth factor down-regulation by TNP-470 in 253J B-V and human umbilical vascular endothelial cells. Docetaxel significantly enhanced in vitro apoptosis by TNP-470 in human umbilical vascular endothelial cells but not in 253J B-V. In vivo combination was most effective when docetaxel was administered before TNP-470, and increased significantly the complete response on tumor growth of nonestablished and established TCCs growing orthotopically into athymic nude mice compared with either therapy alone (P < 0.05). The incidence of spontaneous lymph node metastasis was inhibited completely by the combination therapy (P < 0.05). Drug-induced body weight loss was not significantly different in any treatment groups. The combination of TNP-470 and docetaxel inhibited intratumor neovascularization, the expression of bFGF and matrix metalloproteinases type-9 compared with controls (P < 0.005), and enhanced apoptosis in tumors compared with each therapy alone (P < 0.005). These studies indicate that docetaxel markedly enhances the ability of TNP-470 to inhibit tumorigenicity and metastasis in both nonestablished and established TCCs. These effects are mediated, in part, by the complementary cytotoxicities of angiogenesis inhibition, down-regulation of bFGF and matrix metalloproteinases type-9, and induction of apoptosis.
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PMID:Docetaxel enhances the therapeutic effect of the angiogenesis inhibitor TNP-470 (AGM-1470) in metastatic human transitional cell carcinoma. 1257 64