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)

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

This article deals with new antitumor agents currently in Phase I or II evaluation in various European centers. Drugs reviewed in this article include Taxotere, Camptothecin analogues, CPT-11, and Topotecan. Rhizoxin, D1694, and Bryostatin are among other agents reviewed in this article.
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PMID:New drugs in clinical development in Europe. 804 Jan 42

Five promising new drugs for gynecological cancer were reviewed. Taxans (Paclitaxel: Taxol and Docetaxel: Taxotere) diterpenoid plant products enhance the polymerization of tublin. Taxol showed significant activity for platinum refractory ovarian cancer in a phase 1 clinical trial in the United States. The combination with cisplatin (CDDP) showed superior results to CDDP plus Cyclophosphamide and has been recognized as a new standard in adjuvant chemotherapy for advanced ovarian cancer. The major toxicities are myelosuppression, alopecia, and hypersensitivity reactions (HSRs). HSRs were overcome by pretreatment with anti-histamines and over 24 hours administration. It was also reported that Taxol was administered safely by over 3 hours infusion with reduced myelotoxicity, but the incidence of HSRs may be increased. Clinical trials of intraperitoneal administration and combination with Carboplatin (CBDCA) are ongoing. Taxotere, an analog of Taxol, is also effective as Taxol with a low incidence of HSRs. Topoisomerase inhibitors (Irinotecan hydrochloride: CPT-11 and Topotecan) have promising antitumor activity for ovarian and cervical cancer. CPT-11 is a semisynthetic camptothesin analog developed in Japan. It was also effective for platinum-resistant ovarian cancer, such as mucinous and clear cell carcinoma. An adverse effect was observed in the combination of CPT-11 and CDDP. The phase 1 clinical trial showed a 40% response rate against recurrent ovarian cancer. CPT-11 50-60 mg/m2 (day 1,8,15) and CDDP 50-60 mg/m2 (day 1) are a recommended schedule. The major toxicities are neutropenia and diarrhea. Thrombocytopenia is not severe and diarrhea is also controllable. Topotecan is also a promising topoisomerase inhibitor and reported superior result to Taxol for platinum refractory ovarian cancer. A phase II trial is ongoing for ovarian and cervical cancer in Japan. Nedaplatin, a new analog of cisplatin, has similar activity especially for cervical cancer with less myelotoxicity and nephrotoxicity.
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PMID:[Promising new drugs for gynecological cancer]. 935 Feb 38

The treatment of cancer has developed substantially from its conception in the first years of the 20th century. Since the introduction of alkylating agents during second World War, the oncology specialty has markedly grown. In the recent years, new drugs have been approved for the treatment of cancer. Such examples include the taxanes (Docetaxel and Paclitaxel), Vinorelbine, Irinotecan, Topotecan, Gemcitabine and Gliadel. We will discuss these new chemotherapuetic agents, their pharmacology, indications, toxicity and appropriate dosing. There is no doubt that further clinical research is needed to determine the optimal use of these agents.
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PMID:Recent advances in cancer therapy. 941 30

Several new chemotherapy agents show varying degrees of activity in head and neck cancer. The most extensively studied and most promising agents at this time are the taxanes, particularly paclitaxel. Its exact role in combination with other chemotherapeutic agents or with radiation is still being clarified in clinical testing, but it is certainly reasonable to use paclitaxel for palliation of metastatic or recurrent disease. Docetaxel is a more recently developed agent, and more information regarding its use in palliative therapy will be forthcoming as results from the international randomized trial become available. Gemcitabine has shown very modest activity when used as a single agent or in combination therapy, although further data from ongoing research have not yet been reported. It is an extraordinarily potent radiosensitizer in the head and neck, but unfortunately it appears to have a very narrow therapeutic ratio and should certainly not be used with radiation outside of a clinical trial with careful monitoring of toxicity. Topotecan does not appear to be a clinically useful single agent in treating head and neck cancer, and vinorelbine has shown minimal activity in the few clinical trials that have been conducted in head and neck cancer. Nedaplatin is a very new drug, and it is not possible to draw conclusions regarding its effectiveness until further evaluation has been completed. Continued investigation of new chemotherapeutic agents in head and neck cancer is needed.
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PMID:Chemotherapy in head and neck cancer. Overview of newer agents. 1049 11

Topotecan (TPT) is a DNA-Topoisomerase I poison that exhibits antitumor activity. TPT, like other DNA-damaging agents, arrests or delays cell cycle progression during S- and G2-phase in a wide variety of tumor-derived cell lines. Particularly, the G2-arrest gives time for the cell to repair its DNA lesions prior to starting a new cell cycle. Based on these observations, we assessed the interaction between TPT and G2/M-active agents in p53-mutated cell lines of diverse origin in order to achieve cell toxicity. Two short-term sequential schedules were administered (TPT --> G2/M-active drug at the interval of greatest TPT-induced G2/M-phase cell arrest, and G2/M-active drug --> TPT), in three human tumor-derived cell lines with proven sensitivity to the following drugs: Bleomycin in HEp-2 (squamous larynx carcinoma); Docetaxel in SKBr-3 (breast adenocarcinoma); Etoposide in NCI-H23 (non-small-cell lung cancer). Our results show that: 1) Sequential TPT --> G2/M-active drugs are synergistic when administration overlapped the maximum percentage of TPT-induced G2/M-phase cell arrest interval in all three mutated p53 cell lines; 2) the reverse sequential schedule (G2/M-active drug --> TPT) was antagonistic, and being only additive for Etoposide --> TPT association. In conclusion, our findings further support the potential cytotoxic role of TPT in combination with other active drugs when the correct schedule of administration is applied. In addition, they provide a rationale for new applications in clinical trials using short-term sequential TPT --> G2/M-active drugs.
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PMID:Cytotoxic effects of topotecan combined with various active G2/M-phase anticancer drugs in human tumor-derived cell lines. 1085 93

The purpose of this study was to examine the antiproliferative potentialities of a pool of new generation compounds (Paclitaxel, Docetaxel, Gemcitabine, Topotecan, SN-38) together with fenretinide, a synthetic derivative of retinoic acid, in comparison with the current first choice treatment cisplatin molecule, on a pool of human malignant pleural mesothelioma cell lines derived from either bioptic and pleural effusions samples. To evaluate the chemosensitivity features of malignant mesothelioma cells in vitro, we resorted to a rapid and reproducible colorimetric assay, a useful widely recognized tool for preclinical drug screening. In addition, by DNA content analysis and cellular morphologic assessment, we focused on the apoptosis as a potential mechanism of drug activity. The main results clearly indicate that, in all the models of malignant mesothelioma we handled in vitro, each tested antineoplastic agent is more powerful than cisplatin in inhibiting cell proliferation. Moreover, on experimental evidences basis, we can assume that the cytotoxic activity of tested compounds could be related, at least partially, to the drug-induced programmed cell death. This experimental study gives substance to the expected pharmacologic worth of the second generation antineoplastic drugs even if, in order to afford the most satisfactory biopharmacological approach, allowing to bypass the refractoriness to chemotherapy of this highly lethal tumour, further investigations at preclinical level are required.
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PMID:Enhanced effectiveness of last generation antiblastic compounds vs. cisplatin on malignant pleural mesothelioma cell lines. 1289 25

This study compared the short-term efficacies of different chemotherapy regimens in the treatment of advanced ovarian cancer (AOC) through pair-wise and network meta-analyses (NMA). Randomized controlled trials (RCTs) identified in a comprehensive online literature search met our inclusion criteria. Direct and indirect evidence was combined to compare odds ratios (OR) and surfaces under the cumulative ranking curves (SUCRA) across the different treatment regimens. Twelve eligible RCTs were finally included, involving eight regimens (Paclitaxel + Carboplatin [PC], Gemcitabine + Carboplatin [GC], Carboplatin, Pegylated Liposomal Doxorubicin + Carboplatin [PLD + Carboplatin], Paclitaxel, Paclitaxel + Carboplatin + Topotecan [PC + Topotecan], Paclitaxel + Carboplatin + Epirubicin [PC + Epirubicin] and Docetaxel + Carboplatin [DC]). The NMA results revealed that in terms of overall response rate (ORR) and disease control rate (DCR), PC (ORR: OR=2.59, 95%CI=1.20-6.22; DCR: OR=2.58, 95%CI=1.05-6.82) and GC (ORR: OR=2.08, 95%CI=1.08-4.37; DCR: OR=2.43, 95%CI=1.07-5.80) were more effective against AOC than Carboplatin alone. Similarly, PC (OR=0.21, 95%CI=0.05-0.69), GC (OR=0.31, 95%CI=0.09-0.90) and PLD + Carboplatin (OR=0.22, 95%CI=0.04-0.92) slowed disease progression better than Carboplatin alone. We also found that PC was more efficacious against AOC than Carboplatin or Paclitaxel single-agent chemotherapy. Combination chemotherapy is thus recommended for AOC, and should guide subsequent drug development and treatment strategies.
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PMID:A network meta-analysis of eight chemotherapy regimens for treatment of advanced ovarian cancer. 2783 12