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Hepatic intraarterial chemotherapy with gemcitabine in patients with unresectable cholangiocarcinomas and liver metastases of pancreatic cancer: a clinical study on maximum tolerable dose and treatment efficacy

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Abstract

Purpose

To define the maximum tolerated dose (MTD) of hepatic intraarterial chemotherapy with gemcitabine, administered with and without starch microspheres, in patients with inoperable intrahepatic cholangiocarcinomas and liver metastases of pancreatic carcinomas.

Methods

Gemcitabine was administered on days 1 and 8 with intervals of 2 weeks between the cycles. In group A the initial gemcitabine dose of 1,000 mg/m2 (without microspheres) was increased in 200-mg/m2 steps up to a maximum dose of 2,000 mg/m2. In group B the MTD with microspheres was assessed by giving an additional microsphere dose according to tumor extent and body weight, increasing gemcitabine starting from a dose-step below the MTD with microspheres. The MTD was evaluated via clinical and laboratory findings.

Results

Twenty-four patients were enrolled (12 males, 12 females, mean age 59.17 years; intrahepatic cholangiocarcinoma: n = 17, liver metastases of pancreatic carcinoma: n = 7). The MTD of gemcitabine without microspheres was reached at 1,400 mg/m2, and of gemcitabine with microspheres at 1,800 mg/m2. The comparative evaluation revealed statistically significant better data for the time to progression (p < 0.01) and survival for the group with microspheres (6.8 and 20.2 months) in comparison to the group without microspheres (4.2 and 13.5 months).

Conclusion

This clinical study indicates that the intraarterial application of gemcitabine with doses higher than the recommended 1,000 mg/m2 is well tolerated if combined with microspheres, and yields respectable results in patients who do not respond to systemic chemotherapy.

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Authors and Affiliations

  1. Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Clinic, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany

    Thomas J. Vogl, Wolfram Schwarz, Katrin Eichler, Kathrin Hochmuth, Renate Hammerstingl, Stephan Zangos & Matthias Heller

  2. Department of Oncology Heilbrunn, Oncological Clinic Heilbrunn Leonardis Clinic, Abt-Walther-Weg 15-16, 83670, Bad Heilbrunn, Germany

    Ursula Jacob & Albert Scheller

Authors
  1. Thomas J. Vogl
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  2. Wolfram Schwarz
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  3. Katrin Eichler
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  4. Kathrin Hochmuth
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  5. Renate Hammerstingl
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  6. Ursula Jacob
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  7. Albert Scheller
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  8. Stephan Zangos
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  9. Matthias Heller
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Correspondence to Thomas J. Vogl.

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Albert Scheller has recently died.

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Vogl, T.J., Schwarz, W., Eichler, K. et al. Hepatic intraarterial chemotherapy with gemcitabine in patients with unresectable cholangiocarcinomas and liver metastases of pancreatic cancer: a clinical study on maximum tolerable dose and treatment efficacy. J Cancer Res Clin Oncol 132, 745–755 (2006). https://doi.org/10.1007/s00432-006-0138-0

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  • DOI: https://doi.org/10.1007/s00432-006-0138-0

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