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Byline: Robert P. Whitehead (1), Jacqueline K. Benedetti (2), James L. Abbruzzese (3), Bach Ardalan (4), J. Wendall Goodwin (5), Stanley P. Balcerzak (6), Wolfram E. Samlowski (7), Heinz-Josef Lenz (8), John S. Macdonald (9) Keywords: 5-FU; leucovorin; PALA; pancreas cancer; phase II 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/m.sup.2 given concurrently with leucovorin at 500 mg/m.sup.2. 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/m.sup.2 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. Author Affiliation: (1) University of Texas Medical Branch, Galveston, TX (2) Southwest Oncology Group Statistical Center, Seattle, WA (3) University of Texas, MD Anderson Cancer Center, Houston, TX (4) School of Medicine, University of Miami, Miami, FL (5) Ozarks Regional Clinical Oncology Program, USA (6) Ohio State University Health Center, Columbus, OH (7) University of Utah Health Sciences Center, Salt Lake City, UT (8) University of Southern California School of Medicine, Los Angeles, CA (9) St. Vincent's Comprehensive Cancer Center, New York, NY Article History: Registration Date: 21/10/2004

Byline: Wolfram E. Samlowski (1), Holly Gundacker (2), J. Philip Kuebler (3), Jeffrey K. Giguere (4), Glenn M. Mills (5), David E. Schuller (6), John F. Ensley (7) Keywords: gemcitabine; squamous cell carcinoma; phase II trial Abstract: A phase II trial of gemcitabine(Gemzar(r)), a nucleoside analogue with broadactivity in solid tumors, was performed inpatients with recurrent or metastaticsquamous cell carcinoma of the head andneck. A total of 26 eligible patients wereregistered to receive a dose of1250 mg/m.sup.2 weekly for 3 weeks,followed by a 1 week rest. Toxicity wasevaluable in 26 patients. Nausea andvomiting occured in 11 and 6 patients,repectively. Grade 3 or 4 hematologictoxicities were infrequent. Two patientsdeveloped neutropenic infections. Onepatient developed fatal liver failure whichwas thought due to progressive livermetastases or infection 14 days after asingle dose of gemcitabine. There were noobjective treatment responses (95% CI0--13%), with a median survival of 6 monthsin this highly resistant diseasepopulation. Gemcitabine is not consideredactive enough as monotherapy for furtherevaluation in this disease population. Author Affiliation: (1) Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, U.S.A. (2) Southwest Oncology Group Statistical Center, Seattle, WA, U.S.A. (3) Columbus CCOP, Columbus, OH, U.S.A. (4) Greenville CCOP, Greenville, SC, U.S.A. (5) Louisiana State University Medical Center, Shreveport, LA, U.S.A. (6) Ohio State University Health Center, Columbus, OH, U.S.A. (7) Wayne State University Medical Center, Detroit, MI, U.S.A. Article History: Registration Date: 11/10/2004

Byline: Wolfram E. Samlowski (1), Danika Lew (2), Philip J. Kuebler (3), Michael A. Kolodziej (4), Jesus E. Medina (5), Kenneth F. Mangan (6), Dennis F. Moore (7), David E. Schuller (8) Keywords: Tomudex; squamous cell carcinoma Abstract: A phase II trial of Tomudex (raltitrexed, ZD 1694), a new thymidylate synthase inhibitor, was performed in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. This trial demonstrated that Tomudex was well tolerated in this patient population. Nausea and vomiting were minimal, and hematologic toxicities were relatively infrequent. Only one patient was withdrawn from the study due to toxicity (grade 4 diarrhea). One patient exsanguinated from a rent in the carotid artery in an area of tumor involvement, and was categorized as a grade 5 toxicity. Thus 25/27 patients were able to complete at least 2 cycles of treatment. Tomudex demonstrated a 3.7% response rate (95% CI 0.1--19%), with a median survival of 6 months in this highly resistant disease population. Tomudex is not considered active enough as monotherapy for further evaluation in this disease population. Author Affiliation: (1) University of Utah Medical Center, Salt Lake City, UT (2) Southwest Oncology Group Statistical Center, Seattle, WA (3) Columbus CCOP, Columbus, OH (4) University of Oklahoma Health Science Center, Oklahoma City, OK (5) Temple University, Philadelphia, PA (6) Witchita CCOP, Wichita, KS (7) Ohio State University Health Center, Columbus, OH (8) Wayne State University Medical Center, Detroit, MI, USA Article History: Registration Date: 29/09/2004