Phase II trials of dolastatin-10 in advanced pancreaticobiliary cancers.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Kindler, HL; Tothy, PK; Wolff, R; McCormack, RA; Abbruzzese, JL; Mani, S; Wade-Oliver, KT; Vokes, EE

Published Date

  • October 2005

Published In

Volume / Issue

  • 23 / 5

Start / End Page

  • 489 - 493

PubMed ID

  • 16133801

Electronic International Standard Serial Number (EISSN)

  • 1573-0646

International Standard Serial Number (ISSN)

  • 0167-6997

Digital Object Identifier (DOI)

  • 10.1007/s10637-005-2909-x

Language

  • eng