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  • 1
    Electronic Resource
    Electronic Resource
    Phase I and pharmacokinetic studies with the pentacyclic pyrroloquinone mitoquidone (1988)
    Springer
    Cancer chemotherapy and pharmacology 21 (1988), S. 343-346 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Mitoquidone (MTQ) is the first member of a new group of pentacyclic pyrroloquinones developed for clinical evaluation as a potential anticancer agent. MTQ demonstrated good activity in a range of experimental solid tumour models, but was weakly active against standard prescreens such as the P388 murine leukaemia. Bone marrow suppression or other significant toxicity was not observed in preclinical studies. Twenty-seven patients were treated with MTQ given as a 4-h infusion either once every 21 days (150–600 mg/m2), once a week (200 mg/m2 per week), or as 5 daily doses repeated every 28 days (60–180 mg/m2 per day). The major adverse events encountered included nausea and vomiting (in virtually all patients), dyspnoea, tumour-related pain, and thrombocytopenia in several patients with pretreatment bone-marrow impairment. Phase I studies were suspended without a maximum tolerated dose being reached because of formulation difficulties. There were no major responses, although stable disease was observed in a number of patients with gastrointestinal malignancies. Temporary remission of B-symptoms occurred in two patients with lymphoma. The plasma pharmacokinetics of MTQ were investigated using an HPLC assay with fluorescence detection. Linear pharmacokinetics were observed with a terminal plasma half-life of 2.9±2.1 h (n=18 doses). The volume of distribution was 3.4±2.6 l/kg and plasma clearance was 629±469 ml/min per m2. Several soluble analogues with similar antitumour activity are currently under investigation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00264202
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Alternating six-drug combination chemotherapy induction for intermediate and high-grade non-Hodgkin's lymphoma (1989)
    Springer
    Cancer chemotherapy and pharmacology 24 (1989), S. 326-328 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 31 patients with intermediate and high-grade non-Hodgkin lymphomas were treated by a six-drug alternating regime comprising four cycles of 200 mg/m2 i.v. methotrexate on days 8, 15, 28 and 35, 50 mg/m2 i.v. Adriamycin on day 1, 40 mg/m2 oral prednisolone on days 1–7 and 21–27, 120 mg/m2 i.v. etoposide on days 21–23, 600 mg/m2 i.v. cyclophosphamide on day 21 and 1.4 mg/m2 i.v. vincristine on day 1 (MAPECO). In all, 3 patients had stage I disease, 12 stage II, 6 stage III and 10 stage IV. Of 28 evaluable patients, 19 were complete responders (68%) and 9 were partial responders (32%); at 2 years, the actuarial relapse-free survival of the 19 patients achieving complete remission is 80%, and 5 patients remain in complete remission at 3 years. This is a preliminary report of an effective intensive regime with acceptable toxicity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00304767
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    In response to Vriesendorp et al. Prediction of normal tissue damage by cancer chemotherapy (1988)
    Springer
    Cancer chemotherapy and pharmacology 21 (1988), S. 355-355 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00264205
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    Paper (German National Licenses)
    Fulltext
  • 4
    Electronic Resource
    Electronic Resource
    The efficacy and safety of GR38032F in the prophylaxis of ifosfamide-induced nausea and vomiting (1989)
    Springer
    Cancer chemotherapy and pharmacology 24 (1989), S. 137-139 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The novel 5HT3 receptor antagonist GR38032F was evaluated in the control of emesis induced by the cyclophosphamide analogue ifosfamide. At a dose of 4 mg q 6 h, GR38032F was given to six patients receiving their first dose of ifosfamide infusion (4–6 g/m2 over 24 h); over the 42-h study period, major control of retching and vomiting was achieved in five patients. In the second phase of the study six further patients, in whom high-dose metoclopramide had failed to control emesis, were give 8 mg GR38032F q 6 h; major control of emesis was again observed in five patients. Toxicity attributed to GR38032F was minimal. This selective 5HT3 antagonist is effective and safe in the control of ifosfamide-induced emesis, even in patients resistant to high-dose metoclopramide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00263137
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    Paper (German National Licenses)
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  • 5
    Electronic Resource
    Electronic Resource
    Dose intensity of carboplatin in combination with cyclophosphamide or ifosfamide (1990)
    Springer
    Cancer chemotherapy and pharmacology 26 (1990), S. S22 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In two separate studies of patients with ovarian cancer, subjects were treated on a protocol comprising 400 mg/m2 carboplatin in combination with 1 g/m2 cyclophosphamide (group A) or 5 g/m2 ifosfamide with mesna (group B). The dose intensities achieved in group A were 87.2 mg/m2 carboplatin per week and 245.8 mg/m2 cyclophosphamide per week (34 patients). In group B, the dose intensities achieved were 124.1 mg/m2 carboplatin per week and 2,020 mg/m2 ifosfamide per week (25 patients). Two formulae for the prediction of the optimal dose of carboplatin based on renald function and degree of myelosuppression are compared with that based on surface area, and that recently proposed by Calvert is recommended. The importance of dose intensity and the total dose delivered in phase II and III studies is emphasized.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00685411
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  • 6
    Electronic Resource
    Electronic Resource
    Paper one: Resource allocation in cancer medicine: Invest where the benefits are clear (1996)
    Springer
    Health care analysis 4 (1996), S. 19-28 
    Details
    ISSN: 1573-3394
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Conclusions The future clearly lies in restricting the introduction of new treatments into medical practice unless they are beneficial and an improvement over existing compounds, together with a stepwise re-evaluation of current therapies. The days of analogue development which give 10% or 15% improvement in toxicity over existing compounds are no longer acceptable, and resources should be preserved for real advances. These may require support in their development, particularly at the randomised controlled trial level, by government or research institutions in collaboration with industry. Patients in general are now better informed by their physicians, nurse specialists and self-help groups, although few regions have gone as far as Oregon in information dissemination and involvement of patients in resource allocation decisions. We should take comfort from the fact that in spite of all the difficulty, new treatments continue to be developed, reflecting a commitment from the public, government and the private sector for continued progress. The way forward may be challenging, but the medical profession has to demonstrate leadership by countering the short-sightedness and over-regulation which has resulted from the recent economic recession. We should be seen to be acting with foresight in maintaining the quest for real improvement in the best interests of patients. Governments in turn have a responsibility to ensure they maintain independent bodies of professionals who have the qualities of flexibility, critical ability and vision to ensure continued development of high quality care.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02251142
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    Paper (German National Licenses)
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