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.
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 cancerpatients, and 3.0 months and 29% for the hepatobiliarypatients. Median time to progression was 1.3 months for the pancreatic cancerpatients and 1.6 months for the hepatobiliarypatients. CONCLUSIONS:Dolastatin-10 is inactive against hepatobiliary and pancreatic carcinomas.
Authors: H C Pitot; E A McElroy; J M Reid; A J Windebank; J A Sloan; C Erlichman; P G Bagniewski; D L Walker; J Rubin; R M Goldberg; A A Adjei; M M Ames Journal: Clin Cancer Res Date: 1999-03 Impact factor: 12.531
Authors: G P Kalemkerian; X Ou; M R Adil; R Rosati; M M Khoulani; S K Madan; G R Pettit Journal: Cancer Chemother Pharmacol Date: 1999 Impact factor: 3.333
Authors: Lih-Ching Hsu; David E Durrant; Ching-Chun Huang; Nai-Wen Chi; Riccardo Baruchello; Riccardo Rondanin; Cinzia Rullo; Paolo Marchetti; Giuseppina Grisolia; Daniele Simoni; Ray M Lee Journal: Invest New Drugs Date: 2011-06-08 Impact factor: 3.850