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


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.
Kindler
Hedy L
HL
Section of Hematology/Oncology, University of Chicago Medical Center, 5841 South Maryland Avenue, Chicago, IL 60637, USA. hkindler@medicine.bsd.uchicago.edu
Tothy
Peter K
PK
Wolff
Robert
R
McCormack
Richard A
RA
Abbruzzese
James L
JL
Mani
Sridhar
S
Wade-Oliver
Kurombi T
KT
Vokes
Everett E
EE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001650:Bile Duct Neoplasms / Q000188:drug therapy*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D018281:Cholangiocarcinoma / Q000188:drug therapy; D047630:Depsipeptides; D005260:Female; D005706:Gallbladder Neoplasms / Q000188:drug therapy*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D047630:Depsipeptides; D009842:Oligopeptides; C064570:dolastatin 10