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  • etoposide  (2)
  • Key words Irinotecan  (1)
  • anilino analogues of etoposide  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Dose escalation and pharmacokinetic study of irinotecan in combination with paclitaxel in patients with advanced cancer (2000)
    Springer
    Cancer chemotherapy and pharmacology 46 (2000), S. 43-50 
    Details
    ISSN: 1432-0843
    Keywords: Key words Irinotecan ; Paclitaxel ; Combination therapy ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: Based on preclinical data demonstrating synergy between camptothecin analogues and taxanes, we determined the maximum tolerated dose (MTD) of irinotecan that could be given in combination with a fixed dose of paclitaxel of 75 mg/m2, when both drugs were delivered on a weekly schedule. The pharmacokinetics of this combination were explored to determine whether the sequence of administration affected the elimination of irinotecan. Methods: For the first cycle patients with advanced cancer were treated with irinotecan given as a 90-min infusion followed immediately by paclitaxel given at a dose of 75 mg/m2 over 1 h. The sequence of drug administration was reversed in subsequent cycles for most patients. Chemotherapy was given weekly for 4 weeks, followed by a 2-week rest. In selected patients, plasma concentrations of irinotecan were determined by high-performance liquid chromatography during the first 24 h of cycle 1 and after the first dose of cycle 2 to determine whether the order of drug administration affected the elimination of irinotecan, or the toxicologic effects of the chemotherapy. Results: A total of 53 cycles were delivered to 21 patients. Reversible neutropenia was dose-limiting. Suppression of the other blood cell elements was modest. There was one partial response in a man with a previously treated cholangiocarcinoma that lasted 26 weeks. Prolonged stabilization of disease (6 months or more) was observed in five of the patients (24%). At the recommended dose of irinotecan (50 mg/m2), transfusions of red cells and platelets were not required. The sequence of drug administration produced no significant differences in the pharmacokinetic parameters of irinotecan or SN-38, which were similar to the values reported when irinotecan is administered alone. The most prominent nonhematologic toxicities were mild diarrhea and fatigue. Conclusions: The recommended dose of irinotecan on this schedule is 50 mg/m2. The sequence of drug administration affects neither the elimination of irinotecan nor the chemotherapy-related toxicity. This combination is well tolerated and causes minimal clinical side effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800000115
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Antitumor Agents 126. Novel 4β-Substituted Anilino Derivatives of 3′,4′ -O, O-Didemethylpodophyllotoxin as Potent Inhibitors of Human DNA Topoisomerase II (1993)
    Springer
    Pharmaceutical research 10 (1993), S. 343-350 
    Details
    ISSN: 1573-904X
    Keywords: etoposide ; DNA topoisomerase II ; anilino analogues of etoposide ; KB cells ; cytotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A series of derivatives of 3′,4′ 0,0-didemethylpodophyllotoxin have been synthesized and evaluated for their inhibitor activity against neoplastic cell growth (KB) and against human DNA topoisomerase II as well as for their activity in causing cellular protein-linked DNA breakage. The results show that the compounds possessing a 4β-anilino moiety either unsubstituted or substituted at the para (F, COOCH3, COCH3, CN, CH2CN, NO2) or meta (OH) positions or with an ethylenedioxy moiety showed the same or greater activity than etoposide in causing cellular protein-linked DNA breakage and in inhibiting DNA topoisomerase II. However, compared to the corresponding 4′-0-demethyl analogues, the 3′,4′-O,O-didemethyl compounds have a similar potency in inhibition of DNA topoisomerase II but are less active in causing cellular protein-linked DNA breakage. Complete correlation between the three biological activities–cytotoxicity, inhibition of DNA topoisomerase II, and induction of protein-linked DNA breakage–was also not observed. This supports the possibility that the biological determinants of action among these compounds may be different.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018923902760
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    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Antitumor Agents. 125. New 4β-Benzoylamino Derivatives of 4′-O-Demethyl-4-desoxypodophyllotoxin and 4β-Benzoyl Derivatives of 4′-O-Demethylpodophyllotoxin as Potent Inhibitors of Human DNA Topoisomerase II (1993)
    Springer
    Pharmaceutical research 10 (1993), S. 214-219 
    Details
    ISSN: 1573-904X
    Keywords: etoposide ; DNA topoisomerase II ; amino analogues of etoposide ; KB cells ; cytotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A series of 4β-benzoylamino (5-17) derivatives of 4′-O-demethyl-4-desoxypodophyllotoxin and 4β-benzoyl (18-20) derivatives of 4′-O-demethyl podophyllotoxin have been synthesized and evaluated for their inhibitory activity against the human DNA topoisomerase II as well as for their activity in causing cellular protein-linked DNA breakage. Compounds 5-13 and 15-17 are more potent than etoposide in causing DNA breakage, while compounds 9, 10, 13, 14, 16, and 20 are more active than etoposide in their inhibition of the human DNA topoisomerase II. The order for the enzyme inhibitory activity of the derivatives of 4′-O-demethyl-4-desoxypodophyllotoxin is 4β-arylamino 〉 4β-benzylamino 〉 4β-benzoylamino.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018978525533
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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