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Published on: July 31, 2016
Phase II trials of dolastatin-10 in advanced pancreaticobiliary cancers
Hedy L Kindler1, Peter K Tothy, Robert Wolff
1Section of Hematology/Oncology, University of Chicago Medical Center, 5841 South Maryland Avenue, Chicago, IL 60637, USA. hkindler@medicine.bsd.uchicago.edu
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.
Insights
Dolatstatin-10 showed no efficacy in treating advanced pancreatic and hepatobiliary cancers. This marine-derived pentapeptide did not produce objective responses and was associated with significant neutropenia in clinical trials.
Area of Science:
- Oncology
- Pharmacology
- Marine Biotechnology
Background:
- Pancreaticobiliary malignancies exhibit poor response to conventional chemotherapy, necessitating novel therapeutic agents.
- Dolatstatin-10, a pentapeptide from Dolabella auricularia, is a potent antimitotic agent that inhibits microtubule assembly.
- Existing treatments for advanced hepatobiliary and pancreatic cancers are limited, driving research into new drug candidates.
Purpose of the Study:
- To evaluate the efficacy and safety of Dolatstatin-10 in patients with advanced pancreatic adenocarcinoma.
- To assess Dolatstatin-10's effectiveness in patients with advanced hepatobiliary cancers (liver, bile duct, gallbladder).
- To determine if Dolatstatin-10 could offer a new treatment option for these difficult-to-treat cancers.
Main Methods:
- Two parallel Phase II clinical trials were conducted.
- Patients with histologically-confirmed metastatic pancreatic adenocarcinoma or advanced/recurrent hepatobiliary cancers were enrolled.
- Dolatstatin-10 was administered intravenously at 400 microg/m(2) every 21 days, with restaging CT scans every 2 cycles.
Main Results:
- Twenty-seven patients were evaluable for response; no objective responses were observed.
- Grade 3/4 neutropenia occurred in 59% of patients, with 18% experiencing neutropenic fever.
- Median survival was 5.0 months for pancreatic cancer patients and 3.0 months for hepatobiliary patients. Median time to progression was 1.3 and 1.6 months, respectively.
Conclusions:
- Dolatstatin-10 demonstrated inactivity against advanced pancreatic and hepatobiliary carcinomas.
- The study concluded that Dolatstatin-10 is not an effective treatment for these malignancies.
- Further research into alternative novel agents for pancreaticobiliary cancers is warranted.
