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Phase II trials of dolastatin-10 in advanced pancreaticobiliary cancers

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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.

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Author notes

  1. Sridhar Mani

    Present address: Montefiore Medical Center, Bronx, NY

Authors and Affiliations

  1. Section of Hematology/Oncology, University of Chicago, Chicago, IL

    Hedy L. Kindler, Peter K. Tothy, Sridhar Mani, Kurombi T. Wade-Oliver & Everett E. Vokes

  2. MD Anderson Cancer Center, Houston, TX

    Robert Wolff & James L. Abbruzzese

  3. Department of Medicine, University of Chicago, Chicago, IL

    Richard A. McCormack

  4. Section of Hematology/Oncology, University of Chicago Medical Center, 5841 South Maryland Avenue, MC 2115, Chicago, IL, 60637-1470

    Hedy L. Kindler

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  1. Hedy L. Kindler
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  2. Peter K. Tothy
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  3. Robert Wolff
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  4. Richard A. McCormack
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  5. James L. Abbruzzese
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  6. Sridhar Mani
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  7. Kurombi T. Wade-Oliver
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  8. Everett E. Vokes
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Corresponding author

Correspondence to Hedy L. Kindler.

Additional information

Supported in part by National Cancer Institute Grant No. UO1CA63187 -04.

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Kindler, H.L., Tothy, P.K., Wolff, R. et al. Phase II trials of dolastatin-10 in advanced pancreaticobiliary cancers. Invest New Drugs 23, 489–493 (2005). https://doi.org/10.1007/s10637-005-2909-x

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