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A phase II study of high-dose 24 hour continuous infusion 5-FU and leucovorin and low-dose PALA for patients with advanced pancreatic adenocarcinoma: A Southwest Oncology Group Study

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Abstract

Purpose: The purpose of this phase II multi-institutional study was to define the efficacy and toxicity of infusional 5-FU in combination with PALA and leucovorin in patients with advanced pancreatic cancer. Patients and methods: Patients were required to have histologically confirmed pancreatic cancer that was locally advanced, unresectable or disseminated. The treatment regimen consisted of weekly 5-FU 2600 mg/m2 given concurrently with leucovorin at 500 mg/m2. Both drugs were administered by 24-hour continuous infusion. PALA was administered 24 hours prior to the administration of 5-FU/LV at a dose of 250 mg/m2 IV over 15 minutes weekly. Patients were continued on the assigned treatment regimen until progression of disease, unacceptable toxicity, or the patient declined further therapy. Results: This study accrued 30 patients. Four of these patients were ineligible. All 26 eligible patients were evaluated for toxicity. One patient had inadequate assessment of response and was considered a non-responder. Three of the twenty-six eligible patients had partial responses, for a response rate of 12% (95% confidence interval 2% to 30%). All 26 eligible patients have died and the median overall survival was 7 months (95% confidence interval: 5.2 to 9 months). Four patients experienced grade 4 toxicities, including bilirubin increase (2 patients), vomiting (1 patient) and non-local skin ulceration (1). Two patients discontinued therapy due to toxicity. Conclusion: The dual modulation of 5-FU with PALA and leucovorin in the dose and schedule used here, has a response rate similar to other single agents in pancreatic cancer and can result in some long term survival while having relatively mild toxicity.

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Authors and Affiliations

  1. University of Texas Medical Branch, Galveston, TX

    Robert P. Whitehead

  2. Southwest Oncology Group Statistical Center, Seattle, WA

    Jacqueline K. Benedetti

  3. University of Texas, MD Anderson Cancer Center, Houston, TX

    James L. Abbruzzese

  4. School of Medicine, University of Miami, Miami, FL

    Bach Ardalan

  5. Ozarks Regional Clinical Oncology Program, USA

    J. Wendall Goodwin

  6. Ohio State University Health Center, Columbus, OH

    Stanley P. Balcerzak

  7. University of Utah Health Sciences Center, Salt Lake City, UT

    Wolfram E. Samlowski

  8. University of Southern California School of Medicine, Los Angeles, CA

    Heinz-Josef Lenz

  9. St. Vincent’s Comprehensive Cancer Center, New York, NY

    John S. Macdonald

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  1. Robert P. Whitehead
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  2. Jacqueline K. Benedetti
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  4. Bach Ardalan
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  6. Stanley P. Balcerzak
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  7. Wolfram E. Samlowski
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  9. John S. Macdonald
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Whitehead, R.P., Benedetti, J.K., Abbruzzese, J.L. et al. A phase II study of high-dose 24 hour continuous infusion 5-FU and leucovorin and low-dose PALA for patients with advanced pancreatic adenocarcinoma: A Southwest Oncology Group Study. Invest New Drugs 22, 335–341 (2004). https://doi.org/10.1023/B:DRUG.0000026261.76197.54

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  • DOI: https://doi.org/10.1023/B:DRUG.0000026261.76197.54

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