Phase II trials of dolastatin-10 in advanced pancreaticobiliary cancers

Invest New Drugs. 2005 Oct;23(5):489-93. doi: 10.1007/s10637-005-2909-x.


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 microg/m(2) 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.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Bile Duct Neoplasms / drug therapy*
  • Carcinoma, Hepatocellular / drug therapy
  • Cholangiocarcinoma / drug therapy
  • Depsipeptides
  • Female
  • Gallbladder Neoplasms / drug therapy*
  • Humans
  • Liver Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Neutropenia / chemically induced
  • Oligopeptides / adverse effects
  • Oligopeptides / therapeutic use*
  • Pancreatic Neoplasms / drug therapy*


  • Antineoplastic Agents
  • Depsipeptides
  • Oligopeptides
  • dolastatin 10