Investigational New Drugs

, Volume 24, Issue 6, pp 537–542 | Cite as

Phase II trial of PN401, 5-FU, and leucovorin in unresectable or metastatic adenocarcinoma of the stomach: A Southwest Oncology Group study

  • James H. DoroshowEmail author
  • Sheryl McCoy
  • John S. Macdonald
  • Brian F. Issell
  • Taral Patel
  • Patrick W. Cobb
  • Kathleen J. Yost
  • James L. Abbruzzese
Phase II Studies


From February, 2001 to September, 2002, the Southwest Oncology Group (SWOG) accrued 65 patients with advanced gastric adenocarcinoma to a phase II trial of weekly 5-FU, leucovorin, and the orally-administered uridine analog PN401. Of these 65 patients, 57 were assessable for survival and toxicity, which were the endpoints for the study. Treatment consisted of the administration of 1200 mg/m2 of 5-FU, 500 mg/m2 of leucovorin, and 6 grams of PN401 every 8 h, beginning 8 h after the completion of the 5-FU infusion, and continuing for a total of 8 doses (48 grams) during each weekly chemotherapy session. Therapy was delivered for six weeks out of every 8-week treatment cycle. The gastrointestinal toxicity of this regimen was mild with 2 patients experiencing grade 3 stomatitis, and 6 patients having grade 3 diarrhea; and the hematologic toxicity was acceptable with 6 of 57 patients found to have had grade 3 or 4 leukopenia, and 14 of 57 patients experiencing grade 3 or 4 neutropenia. There were two deaths judged possibly related to treatment; one in a patient who experienced a variety of Grade 2 gastrointestinal toxicities and died at home with an unknown cause of death; and a second patient who also died at home, and for whom treatment-related sepsis could not be ruled out. The overall median survival was 7.2 months. The ability to safely deliver twice the usual dose of 5-FU with leucovorin on a weekly schedule suggests that oral uridine analog supplementation with PN401 may enhance the therapeutic index of the fluoropyrimidines.


Gastric cancer 5-FU Leucovorin PN401 


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Copyright information

© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  • James H. Doroshow
    • 1
    Email author
  • Sheryl McCoy
    • 2
  • John S. Macdonald
    • 3
  • Brian F. Issell
    • 4
  • Taral Patel
    • 5
  • Patrick W. Cobb
    • 6
  • Kathleen J. Yost
    • 7
  • James L. Abbruzzese
    • 8
  1. 1.Division of Cancer Treatment and DiagnosisNational Cancer Institute, City of Hope National Medical CenterDuarte
  2. 2.Southwest Oncology Group Statistical CenterSeattle
  3. 3.St. Vincent’s Cancer CenterNew York
  4. 4.University of Hawaii Community Clinical Oncology ProgramHonolulu
  5. 5.Columbus Community Clinical Oncology ProgramColumbus
  6. 6.Montana Cancer Consortium Community Clinical Oncology ProgramBillings
  7. 7.Grand Rapids Community Clinical Oncology ProgramGrand Rapids
  8. 8.MD Anderson Cancer CenterHouston

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