Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Significant prolongation of survival time among the patients with advanced ovarian cancer has been brought under the development of surgery and chemotherapy, but even those with clinical remission shows sometimes recurrence. For the recurrent ovarian cancer patients at present there are no definite strategy to treat the recurrent cases. Under these circumstance, we have reviewed the current treatment of cytoreductive surgery and chemotherapy for the recurrent cases. 1) surgical treatment Generally, in the cases of recurrent ovarian cancer, cytoreductive surgery is required to minimize the residual tumour in the abdomen. But sometimes we can find the distant metastasis including liver, lung, and lymph node. This means that surgery is not sufficient for control of recurrent tumor. Further adjuvant chemotherapy will be required to control metastatic tumors. 2) chemotherapy After the detail assessment of the initial treatment of cases, at first we should think about retreatment with CDDP-based regimen and secondly about dose-intensification of CDDP or CBDCA for the CDDP-resistant cases. And as combination regimens, topoisomerase inhibitors, etoposide or CPT-11 are also preferable to use, alkylating agents such as ifosfamide, 5-fluorouracil, and some current trials with new drug, taxol are effective for recurrent cases. In conclusion, further active chemotherapy using platinum compounds, topoisomerase inhibitors, taxol will be achieved for the control of the recurrent cases of ovarian cancer.
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PMID:[Treatment of recurrent ovarian cancer]. 135 32

Remarkable improvements in primary surgery and chemotherapy for advanced ovarian cancer have been achieved in the last decades. Nevertheless, the majority of patients still develop recurrent disease and ultimately die from ovarian cancer. Evaluation of efficient second-line treatment is of clinical relevance. This review re-analyses the published data of conventional systemic treatment for recurrent and refractory ovarian cancer. Patients were grouped according to prior chemotherapy (with or without platinum; with or without paclitaxel) and according to clinical platinum resistance. Platinum resistance is defined as having progressed during platinum based chemotherapy or having relapsed within 6 months after completion of primary platinum containing treatment. The most favourable results in platinum sensitive ovarian cancer were reported for platinum containing re-induction chemotherapy. Results in platinum refractory ovarian cancer were different. Both hormonal treatment consisting of either tamoxifen or GnRH analogues, and chemotherapy with topoisomerase blocking agents, taxanes, or alkylating agents did show similar results. Unfortunately, there are only limited data from prospectively randomised trials in these patients. Therefore, recommendations remain inconclusive. Retrospective comparisons may help the clinician to chose the currently best available treatment for an individual patient, however, these treatments have to be evaluated in prospectively randomised trials. The protocols of the ongoing studies in refractory or recurrent ovarian cancer of the AGO Ovarian Cancer Study Group are outlined.
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PMID:[Recurrent and 2nd line therapy in ovarian carcinoma: an overview of conventional systemic therapy modalities]. 934 Sep 70

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

A pharmacokinetically guided phase I study of topotecan and etoposide phosphate was conducted in recurrent ovarian cancer. The scheduling of the topoisomerase I and II inhibitors was determined using in vitro activity data. All patients had recurrent disease following prior platinum-containing chemotherapy. Patients had a World Health Organisation performance status of 0-2 and adequate bone marrow, renal and hepatic function. Treatment was with topotecan intravenously for 5 days followed immediately by a 5-day intravenous infusion of etoposide phosphate (EP), with pharmacokinetically guided dose adjustment. Plasma etoposide levels were measured on days 2 and 4 of the infusion. A total of 21 patients entered the study. In all, 48% were platinum resistant and 71% had received prior paclitaxel. The main toxicities were haematological, short lived and reversible. A total of 29% of patients experienced grade 4 thrombocytopenia and 66% grade 4 neutropenia after the first cycle. Neutropenia and thrombocytopenia was dose limiting. The maximum-tolerated dose was topotecan 0.85 mg m(-2) day(-1) days 1-5 followed immediately by a 5-day infusion of EP at a plasma concentration of 1 mug ml(-1). The response rate (RR) was 28% in 18 evaluable patients. There was marked interpatient variability in topoisomerase IIalpha levels measured from peripheral lymphocytes, with no observed increase following topotecan. This regimen of topotecan followed by EP demonstrated good activity in recurrent ovarian cancer and was noncrossresistant with paclitaxel. Both the toxicity and RR was higher than would be expected from the single agent data, in keeping with synergy of action.
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PMID:Pharmacokinetically guided phase I trial of topotecan and etoposide phosphate in recurrent ovarian cancer. 1595 76

This years ASCO-meeting reinforced the trend of the recent years to get off from empirical treatment concepts to tailored and individualized diagnostics and therapy. However, the basis for an individual therapy is a specific molecular diagnostic which can be reflected in the analysis of hormonal receptor, HER-1, HER-2 and topoisomerase IIalpha in breast cancer. All these markers are not only able to prognosticate the course of disease but they also can predict the success of specific treatment approaches. Trastuzumab is standard therapy in HER-2 positive breast cancer both in the adjuvant and palliative setting. But new therapeutic agents, as e. g. lapatinib, are promising in the treatment of HER-2 positive breast cancer even if trastuzumab is failing. Otherwise it might possibly be an alternative option but adequate clinical results have to be awaited. The targeted inactivation of EGFR-related signal transduction pathways by e. g. gefitinib did not show a substantial improvement neither as a single agent nor in combination with endocrine treatment. However, the appropriate subgroup which might benefit from this therapy has to be defined even if molecular data suggest that patients with ER positive and PR negative breast cancer might be such a group. The increasing knowledge in terms of the biology of bone metastasis led to the development of new treatment options as e. g. denosumab, a humanized monoclonal antibody for RANK ligand. Two adjuvant cytotoxic treatment trials revealed that taxanes improve the prognosis of node positive breast cancer and should be administered sequentially. The advantage of switching to an aromatase inhibitor after two to three years of tamoxifen in endocrine treatment of postmenopausal patients is proved by two clinical trials (IES, ARNO) which could demonstrate a survival benefit. In conclusion it seems to be evident that new targeted therapy options are effective and will set new standards for the treatment of breast cancer patients in the near future. The presentation for the ovarian cancer focused on the addition of a third cytotoxic agent to carboplatin and paclitaxel as the standard therapy for the primary treatment of ovarian cancer. New data of Bevacizumab in the treatment of primary and recurrent ovarian cancer were presented. However, this is not yet a standard treatment for all patients and needs further investigations within large, multicentre, randomised trials. The lymphonodectomy as part of the primary therapy of the endometrial cancer seems to be a benefit at least in patients with advanced disease or high risk stage I tumours. The adjuvant therapy of uterine sarcomas is still not yet very well investigated and clear. A trial which recruited 12 years demonstrated a benefit in overall survival which has to be interpreted with caution. In this year again there have been registered an increasing number of interesting contributions from Germany, which also received international attention.
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PMID:[Molecular diagnostic and targeted therapy--"Barking dogs are going to bite": presentations from the 42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta 2006]. 1700 57

The topoisomerase I agents are established as a therapy in recurrent ovarian cancer. Karenitecin, an analog of topotecan with solubility and pharmacologic advantages, was tested in a phase II trial in previously treated patients with recurrent or persistent ovarian cancer. The drug was administered intravenously over 1 h at a dose of 1.0 mg/m(2) daily for 5 days every 21 days. Patients were treated until disease progression, intolerable toxicity, or voluntary withdrawal. Response was evaluated according to modified RECIST criteria. Twenty-seven patients were entered into the study. One patient was inevaluable for not receiving any treatment. Of the 26 evaluable patients, there were two partial responses and one complete response for a total response rate of 12%. This response rate was insufficient to justify accrual to the second stage. The most common grade 3 or 4 toxicities were neutropenia (19%) and gastrointestinal (15%). Karenitecin is a well-tolerated topoisomerase compound but has minimal activity in extensively pretreated ovarian cancer with the dose-schedule employed.
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PMID:Phase II multicenter open-label study of karenitecin in previously treated epithelial ovarian and primary peritoneal cancer: a Gynecologic Oncology Group Study. 1785 32