Pharmacokinetics, immunogenicity and safety of bivatuzumab mertansine, a novel CD44v6-targeting immunoconjugate, in patients with squamous cell carcinoma of the head and neck

  • Authors:
    • Alexander Sauter
    • Charlotte Kloft
    • Silke Gronau
    • Felix Bogeschdorfer
    • Thomas Erhardt
    • Wolfram Golze
    • Carsten Schroen
    • Alexander Staab
    • Herbert Riechelmann
    • Karl Hoermann
  • View Affiliations

  • Published online on: April 1, 2007     https://doi.org/10.3892/ijo.30.4.927
  • Pages: 927-935
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Abstract

The prodrug bivatuzumab mertansine (BIWI 1) is a novel CD44v6-targeting humanized monoclonal antibody coupled to the toxin mertansine. In a phase I dose escalation trial 31 patients with squamous cell carcinomas of the head and neck were treated with doses of 25-325 mg/m2 as a 30-min infusion. Thirteen patients received a second infusion after 3 weeks. Serial serum samples were collected to determine the pharmacokinetic parameters of the prodrug BIWI 1 and of deconjugated BIWI 1 as well as the occurrence of anti-BIWI 1 antibodies. The maximum tolerated dose was reached at 300 mg/m2 attributable to skin toxicity. No immune response was observed in any patient. For BIWI 1 and deconjugated BIWI 1, clearance values were low and distribution was limited resulting in half-lives of ≈3-3.5 days and ≈6-7 days, respectively, for single and repeated dosing after three weeks. Overall, interindividual variability of the pharmacokinetic parameters was low. In general, the pharmacokinetics of both compounds after single and repeated dosing was comparable across the entire dose range and no significant accumulation took place. Over the dose range investigated, a dose proportional increase in the exposure of BIWI 1 and deconjugated BIWI 1 was observed. Dose individualization according to body size (weight or body surface area) was found to be appropriate and is recommended for the novel immunoconjugate.

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April 2007
Volume 30 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Sauter, A., Kloft, C., Gronau, S., Bogeschdorfer, F., Erhardt, T., Golze, W. ... Hoermann, K. (2007). Pharmacokinetics, immunogenicity and safety of bivatuzumab mertansine, a novel CD44v6-targeting immunoconjugate, in patients with squamous cell carcinoma of the head and neck. International Journal of Oncology, 30, 927-935. https://doi.org/10.3892/ijo.30.4.927
MLA
Sauter, A., Kloft, C., Gronau, S., Bogeschdorfer, F., Erhardt, T., Golze, W., Schroen, C., Staab, A., Riechelmann, H., Hoermann, K."Pharmacokinetics, immunogenicity and safety of bivatuzumab mertansine, a novel CD44v6-targeting immunoconjugate, in patients with squamous cell carcinoma of the head and neck". International Journal of Oncology 30.4 (2007): 927-935.
Chicago
Sauter, A., Kloft, C., Gronau, S., Bogeschdorfer, F., Erhardt, T., Golze, W., Schroen, C., Staab, A., Riechelmann, H., Hoermann, K."Pharmacokinetics, immunogenicity and safety of bivatuzumab mertansine, a novel CD44v6-targeting immunoconjugate, in patients with squamous cell carcinoma of the head and neck". International Journal of Oncology 30, no. 4 (2007): 927-935. https://doi.org/10.3892/ijo.30.4.927