GLORIA

GEOMAR Library Ocean Research Information Access

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Electronic Resource
    Electronic Resource
    Clinical and pharmacology study of chloroquinoxaline sulfonamide given on a weekly schedule (1995)
    Springer
    Cancer chemotherapy and pharmacology 35 (1995), S. 483-488 
    Details
    ISSN: 1432-0843
    Keywords: Key words Chloroquinoxaline sulfonamide ; Pharmacokinetics ; Chemotherapy ; Phase I trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The in vitro human tumor colony-forming assay identified chloroquinoxaline sulfonamide (CQS) as an active agent at human plasma concentrations of 〉100 μg/ml. In the initial phase I trial of CQS given every 28 days, peak plasma concentrations 〉 500 μg/ml were associated with reversible dose-limiting hypoglycemia and occasional cardiac arrhythmias. Therefore, we evaluated whether a weekly schedule of treatment might minimize the drug-associated toxicity while maintaining potential therapeutic concentrations. CQS was given intravenously over 1 h once per week for 4 weeks to 12 patients, beginning at a dose of 2,000 mg/m2. All patients underwent monitoring for cardiac arrhythmias and hypoglycemia. Plasma drug levels were measured following each dose. Mild hypoglycemia was the most common adverse effect. A median nadir plasma glucose concentration of 56 mg/dl was observed at a weekly dose of 2,500 mg/m2. Two patients experienced cardiac dysrhythmia while on study. Continuous electrocardiographic monitoring failed to identify any significant infusion-related arrhythmia. The median CQS plasma concentration measured 24 h following a 2,000-mg/m2 dose of CQS was 〉100 μg/ ml, and the cumulative area under the concentration x time curve (AUC) determined at concentrations of ≥100 μg/ml was similar to that observed with the every-28-day schedule. The weekly schedule described herein appears to maximize the plasma AUC with an acceptable margin of safety. The recommended phase II dose and schedule for CQS is 2,000 mg/m2 given once per week. Although severe hypoglycemia is unlikely, glucose monitoring is appropriate for 6 h following CQS administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00686832
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    Clinical and pharmacology study of chloroquinoxaline sulfonamide given on a weekly schedule (1995)
    Springer
    Cancer chemotherapy and pharmacology 35 (1995), S. 483-488 
    Details
    ISSN: 1432-0843
    Keywords: Chloroquinoxaline sulfonamide ; Pharmacokinetics ; Chemotherapy ; Phase I trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The in vitro human tumor colony-forming assay identified chloroquinoxaline sulfonamide (CQS) as an active agent at human plasma concentrations of 〉100 μg/ml. In the initial phase I trial of CQS given every 28 days, peak plasma concentrations 〉500 μg/ml were associated with reversible dose-limiting hypoglycemia and occasional cardiac arrhythmias. Therefore, we evaluated whether a weekly schedule of treatment might minimize the drug-associated toxicity while maintaining potential therapeutic concentrations. CQS was given intravenously over 1 h once per week for 4 weeks to 12 patients, beginning at a dose of 2,000 mg/m2. All patients underwent monitoring for cardiac arrhythmias and hypoglycemia. Plasma drug levels were measured following each dose. Mild hypoglycemia was the most common adverse effect. A median nadir plasma glucose concentration of 56 mg/dl was observed at a weekly dose of 2,500 mg/m2. Two patients experienced cardiac dysrhthmia while on study. Continuous electrocardiographic monitoring failed to identify any significant infusion-related arrhythmia. The median CQS plasma concentration measured 24 h following a 2,000-mg/m2 dose of CQS was 〉100 μg/ml, and the cumulative area under the concentration x time curve (AUC) determined at concentrations of ≥100 μg/ml was similar to that observed with the every-28-day schedule. The weekly schedule described herein appears to maximize the plasma AUC with an acceptable margin of safety. The recommended phase II dose and schedule for CQS is 2,000 mg/m2 given once per week. Although severe hypoglycemia is unlikely, glucose monitoring is appropriate for 6 h following CQS administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00686832
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Phase II trial of chloroquinoxaline sulfonamide (CQS) in patients with stage III and IV non-small-cell lung cancer (1997)
    Springer
    Cancer chemotherapy and pharmacology 40 (1997), S. 415-418 
    Details
    ISSN: 1432-0843
    Keywords: Key words CQS ; Phase II trial ; NSCLC ; HTCFA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: Chloroquinoxaline sulfonamide (CQS) was one of the first agents identified by the human tumor colony-forming assay (HTCFA) as possessing antitumor activity in non-small-cell lung cancer (NSCLC). Prior phase I studies had suggested that plasma concentrations equivalent to those showing efficacy in the HTCFA could be reliably attained in humans. This phase II study assessed the antitumor activity of CQS while using an adaptive control pharmacokinetic modelling system to attain targeted plasma levels of this novel compound. Methods: A group of 20 patients with stage III or IV NSCLC received CQS as a 1-h weekly infusion at an initial dose of 2 g/m2. In all patients, 24-h plasma concentrations of CQS were measured. Patients with levels 〈100 μg/ml had dose increases determined by their 24-h levels and pharmacokinetic parameters obtained from two prior phase I trials of this agent. These individuals had 24-h CQS levels repeated after their second weeks' treatment and doses were readjusted if the target concentration was not reached. Antitumor response assessment was made every 6 weeks. Results: Of the 20 patients, 18 attained the target plasma concentration, and 16 of these achieved this initially or with just one dose adjustment. No major objective antitumor responses were observed (major response rate 0%, 95% CI 0–17%). CQS was well tolerated with hypoglycemia being the most clinically significant toxicity. Conclusions: When given on this schedule CQS is inactive in NSCLC despite the fact that the target concentration was achieved in 90% of patients. The ability of the HTCFA to identify active agents remains unproved.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800050679
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 4
    Electronic Resource
    Electronic Resource
    Modulation of all-trans retinoic acid pharmacokinetics by liarozole (1994)
    Springer
    Cancer chemotherapy and pharmacology 34 (1994), S. 522-526 
    Details
    ISSN: 1432-0843
    Keywords: Retinoic acid ; Pharmacokinetics ; Liarozole
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Continuous oral dosing with all-trans retinoic acid (RA) is associated with a progressive decrease in plasma drug concentrations that has been linked to relapse and retinoid resistance in patients with acute promyelocytic leukemia (APL). Since oxidation by cytochrome P-450 enzymes is critical in the catabolism of this drug, we evaluated whether pretreatment with an inhibitor of this system, liarozole, could attenuate this phenomenon. A total of 20 patients with solid tumors completed a 4-week course of all-trans RA therapy. On days 1, 2, 28, and 29, serial plasma samples were obtained from these patients after ingestion of a single oral dose (45 mg/m2) of all-trans RA. On days 2 and 29, liarozole was given 1 h prior to ingestion of all-trans RA at single doses ranging from 75 to 300 mg. The areas under the plasma RA concentration x time curves (AUCs) were then compared in the presence and absence of pretreatment. Following continuous oral treatment, the mean day-28 AUC of all-trans RA was significantly lower than the group mean level on day 1 (504 vs 132 ng h−1 ml−1;P=0.05). This decline in plasma concentrations on day 28 was partially reversed by liarozole, which increased the mean plasma all-trans RA AUC on day 29 to 243 ng h−1 ml−1 (P=0.004). The lowest dose of liarozole that reliably produced this effect was 300 mg. No enhanced toxicity was associated with liarozole administration. We conclude that liarozole at a dose of 300 mg effectively attenuates the induced decline in all-trans RA plasma concentrations that occurs with continuous treatment. This combination may be useful in attenuating or reversing retinoid resistance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00685665
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 5
    Electronic Resource
    Electronic Resource
    Modulation of all-trans retinoic acid pharmacokinetics by liarozole (1994)
    Springer
    Cancer chemotherapy and pharmacology 34 (1994), S. 522-526 
    Details
    ISSN: 1432-0843
    Keywords: Key words: Retinoic acid – Pharmacokinetics – Liarozole
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Continuous oral dosing with all-trans retinoic acid (RA) is associated with a progressive decrease in plasma drug concentrations that has been linked to relapse and retinoid resistance in patients with acute promyelocytic leukemia (APL). Since oxidation by cytochrome P-450 enzymes is critical in the catabolism of this drug, we evaluated whether pretreatment with an inhibitor of this system, liarozole, could attenuate this phenomenon. A total of 20 patients with solid tumors completed a 4-week course of all-trans RA therapy. On days 1, 2, 28, and 29, serial plasma samples were obtained from these patients after ingestion of a single oral dose (45 mg/m2) of all-trans RA. On days 2 and 29, liarozole was given 1 h prior to ingestion of all-trans RA at single doses ranging from 75 to 300 mg. The areas under the plasma RA concentration x time curves (AUCs) were then compared in the presence and absence of pretreatment. Following continuous oral treatment, the mean day-28 AUC of all-trans RA was significantly lower than the group mean level on day 1 (504 vs 132 ng h–1 ml–1; P = 0.05). This decline in plasma concentrations on day 28 was partially reversed by liarozole, which increased the mean plasma all-trans RA AUC on day 29 to 243 ng h–1 ml–1 (P = 0.004). The lowest dose of liarozole that reliably produced this effect was 300 mg. No enhanced toxicity was associated with liarozole administration. We conclude that liarozole at a dose of 300 mg effectively attenuates the induced decline in all-trans RA plasma concentrations that occurs with continuous treatment. This combination may be useful in attenuating or reversing retinoid resistance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00685665
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 6
    Electronic Resource
    Electronic Resource
    Phase II trial of esorubicin (4′deoxydoxorubicin, DxDx) in patients with small cell lung cancer (1991)
    Springer
    Investigational new drugs 9 (1991), S. 187-190 
    Details
    ISSN: 1573-0646
    Keywords: esorubicin ; deoxydoxorubicin ; small cell lung cancer ; phase II trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Esorubicin (4′-deoxydoxorubicin or DxDx) is an analog of doxorubicin with preclinical antitumor activity and no significant cardiotoxicity in model systems. Eleven patients with small cell lung cancer who had previously received chemotherapy were given esorubicin (25 mg/m2 intravenously) every 3 weeks. No major objective responses were observed (95% confidence limits: 0–25%). Nine of the 11 patients had grade 2 or greater toxicity, with 55% of the patients experiencing grade 3 or greater toxicity [myelosuppression (4/11), anemia (2/11) or elevated liver enzymes (3/11)]. Nausea, vomiting, alopecia and intravenous site phlebitis were also seen. Three of the 11 patients received 3 or more course of esorubicin without evidence of significant cardiotoxicity. At this dose and shedule, no significant antitumor response were seen in this population of patients. Esorubicin, with this low response rate and significant toxicity, appears to be of limited utility in this disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00175087
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...