Advertisement

Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

Phase II trial of gemcitabine (2,2′-difiuorodeoxycytidine) in patients with adenocarcinoma of the pancreas

Abstract

Gemcitabine is a novel nucleoside analog which demonstrated a broad spectrum of preclinical acitivity in solid tumor models, and responses in patients with pancreas cancer during phase I evaluation. Patients with measurable adenocarcinoma of the pancreas who had received no previous chemotherapy were eligible for this multicenter phase II clinical trial. Gemcitabine 800 mg/m2 was administered intravenously weekly for 3 consecutive weeks, followed by one week rest, every 4 weeks. Forty-four patients entered the trial; 35 had at least 2 cycles of therapy. Partial response was observed in 5 patients (11%, estimated 95% confidence interval 2–20%), with a median duration of 13 months. All responding patients had stabilization or improvement in performance status. Fourteen patients had stable disease of 4 or more months. The median WBC nadir was 3.8 × 103/μl (range 1.6–9.3) and the median absolute neutrophil (ANC) nadir was 2.0 × 103/μl (range 0.4–7.2). Thrombocytopenia - 100.0 × 103/μl was observed in 15 patients; the median platelet nadir was 123.0 (range 30.0–245.0). All patients experienced a mild to moderate flu-like syndrome. In addition, one patient had a mild hemolytic-uremic syndrome which appeared related to gemcitabine therapy. Gemcitabine demonstrated marginal activity in this resistant neoplasm, without excessive toxicity. Further evaluation, including the use of more intense dosing and/or combination therapy, is warranted.

This is a preview of subscription content, log in to check access.

References

  1. 1.

    Boring CC, Squires TS, Long T: Cancer Statistics. CA 41:19–36, 1991

  2. 2.

    Brennan MF, Kinsella T, Friedman M: Cancer of the Pancreas. In: Debita VT Jr, Hellman S, Rosenberg SA (eds). Cancer: Principles and Practice of Oncology. 3rd edition. Philadelphia: JB Lippincott Company, 800–835, 1989

  3. 3.

    Hertel LW, Boder GB, Kroin JS, Rinzel SM, Poore GA, Todd GC, Grindey GB: Evaluation of the antitumor activity of gemcitabine (2′,2′-difluoro-2′-deoxycytidine). Cancer Res 50:4417–4422, 1990

  4. 4.

    Heinemann V, Hertel L, Grindey GB, Plunkett W: Comparison of the cellular pharmacokinetics and toxicity of 2′,2′-difluorodeoxycytidine and 1-ß-D-arabinofuranosylcytosine. Cancer Res 48:4024–4031, 1988

  5. 5.

    Ghandi V, Plunkett W: Modulatory acitivity of 2′,2′-difluorodeoxycytidine on the phosphorylation and cytotoxicity of arabinosyl nucleosides. Cancer Res 50:3675–3680, 1990

  6. 6.

    Huang P, Chubb S, Hertel LW, Grindey GB, Plunkett W: Action of 2′,2′-difluorodeoxycytidine on DNA synthesis. Cancer Res 51:6110–6117, 1991

  7. 7.

    Data on File. Eli Lilly Company, Indianapolis, IN

  8. 8.

    Abbruzzese JL, Grunewald R, Weeks EA, Gravel D, Adams T, Nowak B, Mineishi S, Tarassoff P, Satterlee W, Raber MN, Plunkett W: A phase I clinical, plasma, and cellular pharmacology study of gemcitabine. J Clin Oncol 9:491–498, 1991

  9. 9.

    Miller AB, Hoogstraten B, Staquet M: Reporting the results of cancer treatment. Cancer 47:207–214. 1981

  10. 10.

    Fleming TR: One-sample multiple testing procedure for phase II clinical trials. Biometrics 38:143–151, 1982

  11. 11.

    Cantrell JE Jr, Philips TM, Schein PS: Carcinoma-associated hemolytic-uremic syndrome: a complication of mitomycin C chemotherapy. J Clin Oncol 5:723–734, 1985

  12. 12.

    Kyriazis AP, Kyriazis AA, Yagoda AA: Enhanced therapeutic effect of cis-diamminodichloroplatinum against nude mouse grown human pancreatic adenocarcinoma when combined with I-B-D arabionfuranosylcytosine and caffeine. Cancer Res 45:6083–6087, 1985

  13. 13.

    Heinemann V, Xu Y-Z, Chubb S, Sen A, Hertel LW, Grindey GB, Plunkett W. Cellular elimination of 2′,2′-difluordeoxycytidine 5′-triphosphate: a mechanism of self-potentiation. Cancer Res 52:533–539, 1992

  14. 14.

    Grunewald R, Kantarjian H, Keating MJ, Abbruzzese J, Tarassoff P, Plunkett W. Pharmacologically directed design of the dose rate and schedule of 2′-2′-difluordexoycytidine (gemcitabine) administration in leukemia. Cancer Res 50:6823–6826, 1990

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Casper, E.S., Green, M.R., Kelsen, D.P. et al. Phase II trial of gemcitabine (2,2′-difiuorodeoxycytidine) in patients with adenocarcinoma of the pancreas. Invest New Drugs 12, 29–34 (1994). https://doi.org/10.1007/BF00873232

Download citation

Key words

  • pancreas
  • adenocarcinoma
  • gemcitabine
  • 2,2′-difluorodeoxycytidme
  • phase II