Phase I/II trial of dexverapamil, epirubicin and granulocyte/macrophage-colony-stimulating factor in patients with advanced pancreatic adenocarcinoma

W. Scheithauer, G. Kornek, M. Raderer, K. Koperna-Mach, C. Müller, J. Karner, J. Kastner, C. Tetzner

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

A group of 28 previously untreated patients with locally advanced or metastatic adenocarcinoma of the pancreas were entered in this phase I/II study. Treatment consisted of oral dexverapamil 1000-1200 mg/day for 3 days, epirubicin given as an intravenous bolus injection on day 2 with a starting dose of 90 mg/m2, and 400 μg granulocyte/macrophage-colony-stimulating factor (GM-CSF) administered subcutaneously from day 5 through 14. Epirubicin dose escalation levels were 90, 105, 120 and 135 mg/m2. Consecutive cohorts of 4-8 patients were planned at each dose level. Treatment cycles were repeated every 3 weeks. Haematological toxicity, specifically granulocytopenia constituted the dose-limiting toxicity with a maximum tolerated dose of 120 mg/m2 for epirubicin. Despite routine supportive therapy with GM-CSF, 4, 2, and 5 patients experienced grade 4 granulocytopenia during their first two treatment courses at levels of 105, 120, and 135 mg/m2 respectively. Non-haematological toxicity was uncommon, generally modest, and did not demonstrate a clear relationship with the anthracycline dose. Dexverapamil-related cardiovascular symptoms occurred frequently, but they never resulted in serious toxicity requiring active medical intervention or permanent discontinuation of therapy. Of the 28 patients, 9 achieved partial responses to this therapy. The recommended dose of epirubicin for this regimen with dexverapamil and GM-CSF is 120 mg/m2 every 3 weeks. Therapeutic results suggest this regimen to be an effective and tolerable treatment strategy in pancreatic cancer, which should be evaluated further.

Original languageEnglish
JournalJournal of Cancer Research and Clinical Oncology
Volume121
Issue number3 Supplement
DOIs
Publication statusPublished - Mar 1995

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Epirubicin
Granulocyte-Macrophage Colony-Stimulating Factor
Verapamil
Adenocarcinoma
Agranulocytosis
Therapeutics
Maximum Tolerated Dose
Anthracyclines
Pancreatic Neoplasms
Intravenous Injections
Pancreas

Keywords

  • Dexverapamil
  • Multidrug resistance
  • Pancreatic cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Phase I/II trial of dexverapamil, epirubicin and granulocyte/macrophage-colony-stimulating factor in patients with advanced pancreatic adenocarcinoma. / Scheithauer, W.; Kornek, G.; Raderer, M.; Koperna-Mach, K.; Müller, C.; Karner, J.; Kastner, J.; Tetzner, C.

In: Journal of Cancer Research and Clinical Oncology, Vol. 121, No. 3 Supplement, 03.1995.

Research output: Contribution to journalArticle

Scheithauer, W. ; Kornek, G. ; Raderer, M. ; Koperna-Mach, K. ; Müller, C. ; Karner, J. ; Kastner, J. ; Tetzner, C. / Phase I/II trial of dexverapamil, epirubicin and granulocyte/macrophage-colony-stimulating factor in patients with advanced pancreatic adenocarcinoma. In: Journal of Cancer Research and Clinical Oncology. 1995 ; Vol. 121, No. 3 Supplement.
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