TY - JOUR
T1 - Phase II trials of dolastatin-10 in advanced pancreaticobiliary cancers
AU - Kindler, Hedy L.
AU - Tothy, Peter K.
AU - Wolff, Robert
AU - McCormack, Richard A.
AU - Abbruzzese, James L.
AU - Mani, Sridhar
AU - Wade-Oliver, Kurombi T.
AU - Vokes, Everett E.
N1 - Funding Information:
∗Supported in part by National Cancer Institute Grant No. UO1CA63187 -04. †Current address: Montefiore Medical Center, Bronx, NY.
PY - 2005/10
Y1 - 2005/10
N2 - 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.
AB - 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.
KW - Cholangiocarcinoma
KW - Dolastatin-10
KW - Gallbladder carcinoma
KW - Hepatobiliary cancer
KW - Hepatocellular carcinoma
KW - Pancreatic adenocarcinoma
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U2 - 10.1007/s10637-005-2909-x
DO - 10.1007/s10637-005-2909-x
M3 - Article
C2 - 16133801
AN - SCOPUS:23844535643
SN - 0167-6997
VL - 23
SP - 489
EP - 493
JO - Investigational New Drugs
JF - Investigational New Drugs
IS - 5
ER -