Investigational New Drugs

, Volume 23, Issue 5, pp 489–493

Phase II trials of dolastatin-10 in advanced pancreaticobiliary cancers

  • Hedy L. Kindler
  • Peter K. Tothy
  • Robert Wolff
  • Richard A. McCormack
  • James L. Abbruzzese
  • Sridhar Mani
  • Kurombi T. Wade-Oliver
  • Everett E. Vokes
Article

Abstract

Background: Pancreaticobiliary malignancies respond poorly to conventional chemotherapy, and novel agents are needed. Dolatstatin-10 is a potent antimitotic pentapeptide isolated from the marine mollusk Dolabella auricularia that inhibits microtubule assembly. We conducted 2 parallel phase II trials of dolastatin-10 in patients with advanced hepatobiliary cancers and pancreatic adenocarcinoma. Patients and methods: Eligible patients had histologically-confirmed metastatic pancreatic adenocarcinoma or metastatic, locally advanced or recurrent cancer of the liver, bile duct or gallbladder, and had received no prior chemotherapy for advanced disease. Dolastatin-10 400 μg/m2 was administered intravenously by bolus every 21 days. Restaging CT scans were obtained every 2 cycles. Results: Twenty-eight patients (16 hepatobiliary, including 7 hepatomas, 6 cholangiocarcinomas, 2 gallbladder carcinomas, and 12 pancreatic carcinomas) enrolled; 27 were evaluable for response. There were no objective responses. Grade 3/4 neutropenia occurred in 59% of patients and neutropenic fever in 18%. Median and 1-year survival were 5.0 months and 17% for the pancreatic cancer patients, and 3.0 months and 29% for the hepatobiliary patients. Median time to progression was 1.3 months for the pancreatic cancer patients and 1.6 months for the hepatobiliary patients. Conclusions: Dolastatin-10 is inactive against hepatobiliary and pancreatic carcinomas.

Keywords

dolastatin-10 hepatobiliary cancer hepatocellular carcinoma cholangiocarcinoma gallbladder carcinoma pancreatic adenocarcinoma 

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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Hedy L. Kindler
    • 1
    • 5
  • Peter K. Tothy
    • 1
  • Robert Wolff
    • 2
  • Richard A. McCormack
    • 3
  • James L. Abbruzzese
    • 2
  • Sridhar Mani
    • 1
  • Kurombi T. Wade-Oliver
    • 1
  • Everett E. Vokes
    • 1
  1. 1.Section of Hematology/OncologyUniversity of ChicagoChicago
  2. 2.MD Anderson Cancer CenterHouston
  3. 3.Department of MedicineUniversity of ChicagoChicago
  4. 4.Montefiore Medical CenterBronx
  5. 5.Section of Hematology/OncologyUniversity of Chicago Medical CenterChicago

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