Article

Investigational New Drugs

, Volume 23, Issue 5, pp 489-493

First online:

Phase II trials of dolastatin-10 in advanced pancreaticobiliary cancers

  • Hedy L. KindlerAffiliated withSection of Hematology/Oncology, University of ChicagoSection of Hematology/Oncology, University of Chicago Medical Center Email author 
  • , Peter K. TothyAffiliated withSection of Hematology/Oncology, University of Chicago
  • , Robert WolffAffiliated withMD Anderson Cancer Center
  • , Richard A. McCormackAffiliated withDepartment of Medicine, University of Chicago
  • , James L. AbbruzzeseAffiliated withMD Anderson Cancer Center
  • , Sridhar ManiAffiliated withSection of Hematology/Oncology, University of Chicago
  • , Kurombi T. Wade-OliverAffiliated withSection of Hematology/Oncology, University of Chicago
  • , Everett E. VokesAffiliated withSection of Hematology/Oncology, University of Chicago

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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