gms | German Medical Science

27. Deutscher Krebskongress

Deutsche Krebsgesellschaft e. V.

22. - 26.03.2006, Berlin

Association of CPT-11 pharmacokinetics and non-hematological toxicity in patients with advanced gastrointestinal cancer and influence of age

Meeting Abstract

  • corresponding author presenting/speaker Ute Merkel - Institut für Klinische Pharmakologie, Universitätsklinikum Jena, Deutschland
  • Katrin Farker - Institut für Klinische Pharmakologie, Universitätsklinikum Jena
  • Mandy Rückert - Institut für Klinische Pharmakologie, Universitätsklinikum Jena
  • Ulrich Wedding - Klinik für Innere Medizin II, Universitätsklinikum Jena
  • Marion Hippius - Institut für Klinische Pharmakologie, Universitätsklinikum Jena
  • Klaus Höffken - Klinik für Innere Medizin II, Universitätsklinikum Jena
  • Annemarie Hoffmann - Institut für Klinische Pharmakologie, Universitätsklinikum Jena

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPE220

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Veröffentlicht: 20. März 2006

© 2006 Merkel et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective: In patients with advanced gastrointestinal cancer, we investigated the association of non-haematological toxicities and the age of patients as well as pharmacokinetic parameters of irinotecan.

Methods: All patients received a chronomodulated infusional regimen consisting of irinotecan , 5-fluorouracil and folinic acid. Non-hematological toxicities (nausea, vomiting, mucositis/stomatitis, diarrhoea, fever, infection, mood alteration, motor neuropathy, sensory neuropathy and general condition) were monitored. The toxicities were evaluated according to NCI-CTCAE version 3.0 and the grading of the general condition was performed according to the performance status (WHO). For the evaluation of the pharmacokinetics of irinotecan blood sampling was performed up to 48 h from the end of infusion. Plasma concentrations of irinotecan were assayed using HPLC with fluorescence detection.

Results: Twenty-eight patients (17 men and 11 women, 27 colorectal cancer) were involved in this investigation. The age of the patients ranged between 38 and 79 years. Observed toxicity was moderate. Grade 4 toxicities of general conditions and mucositis/stomatitis occurred in 14% and 3% of the patients. Grade 3 diarrhoea, a characteristic non-hematological side effect of irinotecan therapy, experienced 18% of the patients. We did not find any association between the age and non-hematological toxicities. Considerable variability in the pharmacokinetic parameters of irinotecan was observed. The age of the patients was not significantly related to any of the studied kinetic parameters and had no effect on the observed variability. Cmax, AUC as well as CL were associated with severity of diarrhoea, nausea and mood alteration.

Conclusion: Our results show that non-hematological toxicities correlated with the pharmacokinetics of irinotecan. That means patients with higher irinotecan systemic exposures had more serious toxicities of diarrhoea, nausea and mood alteration. The findings suggest that age is not a predictor of irinotecan pharmacokinetics. In addition elderly patients have not experienced qualitative and/or quantitative altered non-hematological toxicities after chronomodulated chemotherapy of irinotecan, 5-FU and FS.

This project is supported by German Cancer Aid (grant AZ-70-2445-Hö3).