Phase II trials of dolastatin-10 in advanced pancreaticobiliary cancers

Hedy L. Kindler, Peter K. Tothy, Robert Wolff, Richard A. McCormack, James L. Abbruzzese, Sridhar Mani, Kurombi T. Wade-Oliver, Everett E. Vokes

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)489-493
Number of pages5
JournalInvestigational New Drugs
Volume23
Issue number5
DOIs
StatePublished - Oct 2005

Fingerprint

dolastatin 10
Neoplasms
Pancreatic Neoplasms
Gallbladder
Adenocarcinoma
Bile Duct Neoplasms
Antimitotic Agents
Drug Therapy
Cholangiocarcinoma
Mollusca
Liver Neoplasms

Keywords

  • Cholangiocarcinoma
  • Dolastatin-10
  • Gallbladder carcinoma
  • Hepatobiliary cancer
  • Hepatocellular carcinoma
  • Pancreatic adenocarcinoma

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Kindler, H. L., Tothy, P. K., Wolff, R., McCormack, R. A., Abbruzzese, J. L., Mani, S., ... Vokes, E. E. (2005). Phase II trials of dolastatin-10 in advanced pancreaticobiliary cancers. Investigational New Drugs, 23(5), 489-493. https://doi.org/10.1007/s10637-005-2909-x

Phase II trials of dolastatin-10 in advanced pancreaticobiliary cancers. / Kindler, Hedy L.; Tothy, Peter K.; Wolff, Robert; McCormack, Richard A.; Abbruzzese, James L.; Mani, Sridhar; Wade-Oliver, Kurombi T.; Vokes, Everett E.

In: Investigational New Drugs, Vol. 23, No. 5, 10.2005, p. 489-493.

Research output: Contribution to journalArticle

Kindler, HL, Tothy, PK, Wolff, R, McCormack, RA, Abbruzzese, JL, Mani, S, Wade-Oliver, KT & Vokes, EE 2005, 'Phase II trials of dolastatin-10 in advanced pancreaticobiliary cancers', Investigational New Drugs, vol. 23, no. 5, pp. 489-493. https://doi.org/10.1007/s10637-005-2909-x
Kindler, Hedy L. ; Tothy, Peter K. ; Wolff, Robert ; McCormack, Richard A. ; Abbruzzese, James L. ; Mani, Sridhar ; Wade-Oliver, Kurombi T. ; Vokes, Everett E. / Phase II trials of dolastatin-10 in advanced pancreaticobiliary cancers. In: Investigational New Drugs. 2005 ; Vol. 23, No. 5. pp. 489-493.
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AU - Wolff, Robert

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AU - Abbruzzese, James L.

AU - Mani, Sridhar

AU - Wade-Oliver, Kurombi T.

AU - Vokes, Everett E.

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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.

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