Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antitumor effect of a new derivative of taxol, docetaxel (RP56976), was examined in K562 human tumor system in vitro. K562 cells presenting a multidrug resistant phenotype showed cross resistance to docetaxel. However, the resistance levels of docetaxel in these cell lines were much lower than for adriamycin and vincristine. Flow cytometric analysis showed the accumulation of cells into G2/M phase after 18hrs. Wright-Giemsa staining showed a marked increase of metaphase population. Docetaxel was shown to promote the assembly of microtubule protein without GTP in vitro, but no inhibitory effect on DNA, RNA and protein synthesis. Moreover, topoisomerase activities were not affected by docetaxel. These results indicate that docetaxel acts as a strong mitotic inhibitor in cancer chemotherapy.
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PMID:[Effect of a new anticancer drug, docetaxel (RP56976), on human leukemia cell lines]. 790 6

The pharmacokinetics and metabolism of Taxotere have been studied after intravenous infusion in mice, dogs and cancer patients. Multiphasic disposition profiles have been observed with rapid initial tissue uptake and large distribution volumes. Hepatobiliary extraction is the major route of elimination, with similar metabolic pathways in all the species. In mice, both systemic and tumour exposures increased proportionately with the dose. In phase I studies, Taxotere pharmacokinetics were not dependent on the various administration schedules. After short intravenous infusions of 70-115 mg/m2 every 3 weeks, a three phase disposition profile was observed with a terminal half-life of 12 hours and a plasma clearance of 21 l/hr/m2. A limited sampling strategy has been designed and large scale prospective population pharmacokinetic/pharmacodynamic studies have been implemented in ongoing phase II studies.
Cancer Surv 1993
PMID:Pharmacokinetics and metabolism of Taxotere (docetaxel). 790 50

Taxotere [N-debenzoyl-N-tert-butoxycarbonyl-10-deacetyl taxol] is a new chemical entity obtained by semisynthesis from 10-deacetylbaccatin III, a non cytotoxic precursor extracted from the needles of the European yew Taxus baccata. Taxotere retains the unique mechanism of action of taxol and inhibits the depolymerisation of microtubules into tubulin. In vitro, Taxotere is cytotoxic against murine and human tumor cells with IC50 values ranging from 4 to 35 ng/ml. Taxotere inhibits the clonogenic properties of fresh human tumor cells at clinically relevant concentrations. Taxotere is highly active in vivo against several experimental models: it is 2.7-fold more active than taxol on a log cell kill basis against B16 melanoma; ten out of the twelve models of grafted murine tumors tested respond to Taxotere; it is active with 80% complete regressions against advanced C38 colon adenocarcinoma and PO3 pancreatic ductal adenocarcinoma. Finally, Taxotere is active against several human xenografts implanted in nude mice. Safety studies were performed in dogs and mice according to NCI guidelines. Toxicological effects are observed mostly is tissues with high cell turnover (bone marrow in mice and dogs, gastrointestinal tract in dogs only) or in those where microtubules play an important role (peripheral nerves in mice only). Because of its availability, due to an efficient process using a renewable source of natural precursor, its preclinical profile (higher antitumoral activity than taxol with a comparable toxicological profile) and its unique mechanism of action, Taxotere has entered Phase I clinical trials in Europe, United States and Japan. The dose limiting toxicity is a neutropenia. Evidence of clinical activity has been noted (breast, ovarian, lung). Taxotere is now in Phase II clinical trials.
Bull Cancer 1993 Apr
PMID:[Taxotere: from yew's needles to clinical practice]. 790 95

The taxoids are natural products isolated from the yew tree (Taxaceae). Certain compounds of this family possess interesting antitumour properties. The discovery of one such compound, taxol and the development of an even more active derivative, Taxotere, are described. Taxotere represents a major progress in the domain of cancer chemotherapy.
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PMID:Taxoids, a new class of antitumour agents of plant origin: recent results. 790 40

The in vitro effects of paclitaxel (Tx) and docetaxel (Taxotere, Txt) are compared in this study using the adenosine triphosphate cell viability assay (ATP-CVA) in 14 cancer cell lines. Eleven cell lines were sensitive and three were partially sensitive to paclitaxel. Nine cell lines were sensitive, three were partially sensitive and two were resistant to docetaxel. Mean IC50s were 3.7-660 ng/ml paclitaxel and 5.4-540 ng/ml docetaxel. In five sensitive cancer cell lines docetaxel was more active than paclitaxel, and in six sensitive cell lines paclitaxel was more active than docetaxel on a concentration basis. Two cell lines were sensitive to paclitaxel and resistant to docetaxel. In one cell line the two compounds had similar activities. In the ATP-CVA, paclitaxel and docetaxel are very active and are partially non-cross-resistant.
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PMID:Comparison of paclitaxel and docetaxel (Taxotere) in gynecologic and breast cancer cell lines with the ATP-cell viability assay. 791 Apr 94

Docetaxel (Taxotere) is a new antitumor agent with activity in patients with ovarian, lung and breast cancer. In this study, docetaxel was tested for its antitumor effect in human tumor xenografts derived from head and neck squamous cell carcinoma (HNSCC). A significant growth inhibiting effect was observed in the two tested lines, at the well tolerated dose of 20 m/kg docetaxel. Two intravenous injections were given with a week interval. Both lines were less sensitive to treatment with cisplatin, indicating that no cross-reactivity exists between these drugs. Docetaxel has a promising outlook in the treatment of patients with head and neck squamous cell carcinoma (HNSCC).
Cancer Lett 1994 Jun 30
PMID:The growth inhibiting effect of docetaxel (Taxotere) in head and neck squamous cell carcinoma xenografts. 791 64

From Taxol, Taxotere, and 10-deacetyl baccatin III, a number of compounds have been prepared. Their biological activity was evaluated on microtubule disassembly at 0 degrees C. The conformation of these Taxol and Taxotere analogues was determined by molecular modeling experiments and nuclear magnetic resonance spectroscopy and compared with the structure of Taxotere in the crystal, obtained by an x-ray analysis. The results of these studies given information on the crucial parts of the active molecules involved in the binding to tubulin.
J Natl Cancer Inst Monogr 1993
PMID:Structure-activity relationships of Taxol and Taxotere analogues. 791 33

The effects of taxoids (taxol and Taxotere) were followed on two human cancerous cell lines (bladder carcinoma J82 cells and epidermoid carcinoma KB 3-1 cells). Three cellular parameters were studied, viz., the qualitative effect on cellular microtubules, the quantitation of tubulin, and the antimitotic action, using two-parametric flow-cytometric analyses in treated cells. In both of the cell lines the tubulin content increased after taxoid treatment before the accumulation of cells in the G2/M phase. The effects of taxoids on tubulin appeared at about a 10-fold lower concentration on KB cells than on J82 cells. After drug exposure, the microtubule network showed a striking difference between the two cell lines: microtubule bundles were predominant in the J82 cell line, whereas multiple asters were prevalent in the KB cell line. The formation of these structures was dose- and time-dependent. Asters were observed in mitotic cells and bundles were seen in interphase cells. The reversibility of these structures in both cell lines varied with the duration of exposure to drug. Some differences were shown between taxol and Taxotere: the effects of Taxotere as compared with taxol appeared at a 2-fold lower concentration and their reversibility was slower.
Cancer Chemother Pharmacol 1994
PMID:Comparative effects of taxol and Taxotere on two different human carcinoma cell lines. 791 21

Docetaxel (Taxotere), a new semisynthetic taxoid, is a potentially important chemotherapeutic agent for the treatment of cancer. Forty patients with bidimensionally measurable advanced adenocarcinoma of the colon were treated with docetaxel 100 mg m-2 every 3 weeks as a 1 h infusion without routine premedication. Thirty-nine patients were eligible: 23 males and 16 females. Median age was 60 years (range 41-75) and WHO performance status 1 (0-2). Prior adjuvant chemotherapy was performed in four patients and prior radiotherapy in nine patients. Bidimensionally measurable disease sites included: liver in 26 patients, lymph nodes and abdominal/peritoneal masses in 13, lung/mediastinal masses in ten and subcutaneous nodes in four. The median number of cycles given was 2 (range 1-15). Thirty-three patients were evaluable for response. One patient (3%) achieved a complete response and two (6%) (95% confidence limits 0-14%) a partial response. Side-effects were similar to those observed in other studies. Docetaxel, given at this dosage and schedule, has minimal activity in the treatment of colorectal carcinoma.
Br J Cancer 1994 Aug
PMID:Docetaxel (Taxotere), a novel taxoid, in the treatment of advanced colorectal carcinoma: an EORTC Early Clinical Trials Group Study. 791 19

In a multicentre trial of the EORTC ECTG we have treated 43 non-pretreated patients with advanced non-small-cell lung cancer (NSCLC) with the new semisynthetic taxoid docetaxel (Taxotere). Six patients were ineligible; of the 37 eligible patients, ten had prior radiotherapy and 18 prior surgery. They received 100 mg m-2 in 1 h i.v. every 3 weeks, usually in an outpatient setting. Prophylactic steroids, antihistaminics or antiemetics were not routinely given. Two patients were not evaluable because they withdrew from the study because of a hypersensitivity reaction after the second cycle. The main toxicity was neutropenia (80% of cycles), although infections were rare (4%). One patient died from sepsis during neutropenia. Hypersensitivity reactions necessitating interruption of docetaxel (Taxotere) infusions were found in only 10% of cycles. The overall response rate was 23% with one complete response, and seven partial responses. Stable disease was found in 16 patients. The median duration of response was 36 weeks, and the median survival of all patients was 11 months. Docetaxel (Taxotere) is among the most active drugs for treatment of NSCLC.
Br J Cancer 1994 Aug
PMID:Docetaxel (Taxotere) is active in non-small-cell lung cancer: a phase II trial of the EORTC Early Clinical Trials Group (ECTG) 791 19


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