Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D02165 (Docetaxel)
 1,764 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Taxotere (RP 56976, NSC 628503), an analog of taxol, is an inhibitor of depolymerisation of microtubules and is currently in Phase I clinical trials. Comparisons of the cytotoxicities of Taxotere and taxol have been studied on several murine (P388, SVras) and human cell lines (Calc18, HCT116, T24, N417, KB). Taxotere was found more potent than taxol (1.3-12 fold), a result which could be explained by its higher affinity than taxol for microtubules. In agreement with its postulated mechanism of action, Taxotere is more cytotoxic on proliferating than on non proliferating N417 cells and does not inhibit cellular DNA, RNA and protein synthesis. Taxotere gives partial cross resistance on P-glycoprotein resistant P388/DOX cell line, in contrast to taxol which gives a complete cross resistance. On the other hand, no cross resistances were observed on Calc18/AM and P388/CPT5 cell lines, bearing modified activities of topoisomerase II and topoisomerase I, respectively. These results underline the higher cytotoxic activity of Taxotere compared to taxol, and the lack of cross resistance of that class of agent with the topoisomerase I and II-related multidrug resistance phenotypes.
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PMID:Effects of Taxotere on murine and human tumor cell lines. 138 86

The development of new chemotherapeutic agents for cancer treatment is pursued with the hope of finding compounds with novel chemical characteristics, unique mechanisms of action, and with improved therapeutic indexes. Seven novel agents at different stages of clinical development have been selected for review. D1694 is a thymidylate synthase inhibitor that has intriguing preclinical activity. The anthrapyrazoles consist of three analogues that are undergoing phase II testing at present. One of these agents, CI-941, has been reported to have significant clinical activity in breast cancer. Lometrexol is an inhibitor of glycinamide ribonuclide transformylase, a critical enzyme in purine biosynthesis, that is undergoing phase II testing. Taxotere, a semisynthetic analogue of taxol that stabilizes microtubules, is currently undergoing phase I testing. Gemcitabine, a fluorinated analogue of deoxycytidine that can inhibit ribonucleotide reductase and be incorporated into DNA, is undergoing phase II testing. BMY-25067 is a mitomycin C analogue that is less myelosuppressive and more active than mitomycin C in preclinical models. Topotecan, a topoisomerase I inhibitor, has been shown to cause myelosuppression as the dose-limiting toxicity in phase I testing. Although each of these agents have some unique and novel characteristics that merit their clinical testing, these agents' long-range clinical role will depend on their efficacy in randomized phase III comparative trials.
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PMID:Novel chemotherapeutic agents in clinical development. 168

Several provocative studies in gynecologic cancer were recently presented. Long-term follow-up of ovarian cancer patients has confirmed the clinical impression of a low survival. Novel classes of active chemotherapeutics are the second-generation topoisomerase I inhibitors, irinotecan (CPT-11) and topotecan, and the taxanes, Taxol (Bristol-Meyers, Wallingford, CT) and Taxotere (Rhone-Poulenc Rorer, Antony, France). Dose intensity remains an intriguing issue. Biologic agents, including monoclonal antibodies, are being developed for palliation of ascites. In cervical cancer, use of retinoids and interferons has opened up a new avenue of investigation. Use of the World Health Organization sophisticated scoring criteria has improved the primary treatment of trophoblastic disease. Advances in salvage therapy have been noted. Progress in the treatment of advanced endometrial cancer and uterine sarcomas is beginning.
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PMID:Systemic therapy for gynecologic cancer. 810 75

Non-small cell lung cancer accounts for 75% of all lung tumours, and only about 10% of patients will remain alive 5 years after diagnosis. Few cytotoxic drugs currently registered produce more than a 15% response rate as a single agent or 30%-35% in combination, with only modest survival benefits. New cytotoxic drugs entering phase II and III studies, however, appear to have more than 20% activity against this disease. They include the taxanes (taxol and taxotere), camptothecin analogues (CPT-11 and topotecan), antimetabolites (edatrexate and gemcitabine) and the vinca alkaloid, navelbine. Taxol produces response rates of about 25% in previously untreated patients and is currently undergoing trials at higher doses in combination with cisplatin and granulocyte colony-stimulating factor. Taxotere produces response rates of 33% in previously untreated patients and 21% in patients previously refractory to platinum-containing regimens. The camptothecin analogues, which are inhibitors of topoisomerase I, may produce response rates of up to 41% in previously untreated patients, but these results have varied considerably between different trials (response rates as low as 13.5% have been reported for topotecan). A phase II study with edatrexate produced a response rate of 32% but subsequent trials using combination chemotherapy including this agent have been disappointing. The activity of gemcitabine as a single agent is 20%-25%. Three ongoing phase II studies combining cisplatin and gemcitabine have shown response rates of up to 50%. Gemcitabine has minimal subjective toxicity. Navelbine produces response rates of 22%-33% as a single agent and up to 65% in combination. These new cytotoxic agents with significant activity in non-small cell lung cancer provide exciting potential for developing novel combination regimens in the advanced setting and as neoadjuvant and adjuvant therapy.
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PMID:New drugs in the treatment of non-small cell lung cancer. 869 45

There is a great need for new drugs to treat the increasing numbers of patients with disseminated cancers. Many of the known anticancer drugs, including the taxoids, docetaxel (Taxotere) and paclitaxel (Taxol), are derived from natural products and there will be many more active compounds to be discovered amongst the 300000 plant species available for evaluation. Cytotoxic agents may kill cancer cells by a variety of means. Thymidilate synthase inhibitors such as LY231514 and raltitrexed (Tomudex) have shown activity against a variety of solid tumours including colorectal cancer. The antifolate, trimetrexate, and the nucleoside analogue, gemcitabine, have also shown anticancer activity. Amongst the topoisomerase I inhibitors, CPT-11 is being developed for use against colorectal cancer. Non-cytotoxic agents which interfere with processes such as angiogenesis may also have a role in future treatments for disseminated cancers.
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PMID:The development of new chemotherapeutic agents. 886 8

The increase in our understanding of the mode of action of drugs and their potential interactions is allowing treatment strategies to be designed to optimize efficacy and minimize toxicity. Combination chemotherapy may entail the use of concurrent administration of two or more agents, or sequential or alternating administration of single agents or combinations. It is increasingly important to understand the advantages and disadvantages of each of these strategies, and the influence of each component of a combination therapy. Biochemical modulation is now used to enhance drug efficacy: the metabolism of 5-fluorouracil can be modified using leucovorin, methotrexate and 5-ethynyluracil; etoposide enhances the action of platinum drugs by inhibiting repair of the platinum-damaged DNA; and treatment with topoisomerase I inhibitors can increase sensitivity to topoisomerase II inhibitors. The role of docetaxel in combinations is now under investigation. Docetaxel (Taxotere) has the following features which indicate that it will be a useful drug in combination: the unique mechanism of action of the taxoids; neutropenia as the single dose-limiting toxicity; and a broad spectrum of antitumour activity. Clinical trials are ongoing to examine the use of docetaxel combination regimens in several disease areas.
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PMID:New approaches to the treatment of advanced breast cancer. 886 11

This review presents a synthesis of published studies on the activity of the newer cytotoxic drugs in the treatment of bronchial cancer. It also touches on the early indications of recent results which until now have only been the subject of oral presentations. The taxanes form a new class of anti-cancer drug. Myelosuppression is their limiting factor. These are very active cytotoxic drugs but their toxological profile makes them difficult to use in polychemotherapy. The anti-tumour activity of docetaxel (Taxotere) has been shown. For non-small cell cancer (CNPC) the objective response (OR) is of the order of 26% in new patients and 21% in those who have been pre-treated with a combination of drugs based on Cisplatine. For paclitaxel (Taxol) the OR is around 25% in new patients. In association with a course of cisplatine the efficacy would be dose dependent. For small cell cancer (CPC) it enables a level of OR around 38% as monochemotherapy. Inhibitors of topoisomerase I (topotecan, irinotecan) form another new class of therapy. Myelosuppression again limits their toxicity. Diarrhoea is an additional toxicity of irinotecan (Campto). The inhibitors of topoisomerase I seem particularly active as monochemotherapy in the treatment of smal cell cancer. Haematological toxicity makes them difficult in association. The activity of topotecan (Hycantin) in the treatment of non-small cell carcinoma remains to be studied. For this indication irinotecan would enable an OR of 33% in new patients. The new anti-metabolite, gemcitabine (Gemzar) is characterised by a different mode of action from other cytotoxics used in the treatment of bronchial cancer. For non-small cell carcinoma it is active as monotherapy and in association with cisplatine. Its activity is more modest in the treatment of CPC but few studies are available for this indication. Its toxic profile makes it promising to be used in association. The new spindle drug vinorelbine (Navelbine) is active as monotherapy or associated with cisplatine in the treatment of non-small cell carcinoma. The limiting toxicity is haematological. Its neurotoxicity is moderate compared to agents in the same therapeutic class. These different cytotoxic drugs arouse a ligitimate interest but the optimal therapeutic schemas for their use remain poorly understood (with the exception of vinorelbine). Their place in the therapeutic arsenal remains to be defined whilst waiting for the results of Phase III studies, their routine use cannot be recommended.
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PMID:[New cytotoxics in the treatment of bronchial cancers]. 983 87

The treatment of advanced non-small cell lung carcinoma (NSCLC) has improved greatly over the past decade. With the advent of new agents, in particular taxanes, gemcitabine, vinorelbine, and topoisomerase I inhibitors, response rates have improved from 15-20% to 25-35%, with commensurate improvement in median and one year survival rates to 8-10 months and 35-45%, respectively. These improvements have proven statistically significant in multiple studies [1-4]. Docetaxel, either alone or in combination with platinols, has shown particular promise; and, in some arenas, it has become a standard component of our therapeutic armamentarium. We will review the preclinical data and single agent activity of docetaxel in treatment-naive and previously treated NSCLC patients, its activity in combination with cisplatin and carboplatin, as well as other new agents, and finally focus on ongoing studies evaluating its role in locally advanced disease.
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PMID:Advanced non-small cell lung carcinoma: the emerging role of docetaxel. 1083 Jan 38