Oncology

Review

Gemcitabine: Progress in the Treatment of Pancreatic Cancer

Heinemann V.

Author affiliations

Klinikum Grosshadern, III Medical Clinic, Munich, Germany

Keywords: Clinical benefit responseCombination therapyGemcitabinePalliative chemotherapyPancreatic cancerSingle agentTumor marker

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Oncology 2001;60:8–18
https://doi.org/10.1159/000055290

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Article / Publication Details

First-Page Preview
Abstract of Review

Published online: December 28, 2000
Issue release date: December 2000

Number of Print Pages: 11
Number of Figures: 0
Number of Tables: 7

ISSN: 0030-2414 (Print)
eISSN: 1423-0232 (Online)

For additional information: https://www.karger.com/OCL

Abstract

Unresectable pancreatic cancer has a dismal prognosis with a median survival of 3–5 months in untreated disease. Since the introduction of gemcitabine, pancreatic cancer may no longer be regarded a chemotherapy-resistant tumor. Treatment with single-agent gemcitabine achieved clinical benefit and symptoms improvement in 20–30% of patients. While 1-year survival was observed in 2% of 5-fluorouracil (5-FU)-treated patients, it was raised to 18% by single-agent gemcitabine. Good treatment tolerability and low incidence of side effects are clear advantages of single-agent gemcitabine. Improvement of efficacy is, however, expected from combination treatment. Gemcitabine and cisplatin given as first-line treatment in three studies achieved a median survival of 7.4–8.3 months. One-year survival was raised to 28% as reported in one study. Comparable activity was obtained by a combination of gemcitabine with 5-FU. Nine studies using gemcitabine in combination with standard-dose or high-dose 5-FU reported a median survival ranging from 5.5 to 13 months. Notwithstanding these promising results, recommendations regarding palliative chemotherapy of pancreatic cancer remain tentative and still need confirmation by presently ongoing phase III trials. Inclusion of pancreatic cancer patients into clinical trials should be a major goal. Outside clinical trials, patients should present with an adequate PS (Karnofsky-performance index ≧70) to qualify for chemotherapy.

© 2001 S. Karger AG, Basel



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References

  1. Parker SL, Tong T, Bold S, Wingo PA: Cancer statistics. CA Cancer Clin 1997;47:5–27.
  2. Wanebo HJ, Vezeridis MP: Pancreatic Carcinoma in perspective: A continuing challenge. Cancer 1996;78:580–591.
    External Resources
  3. Moore M: Activity of gemcitabine in patients with advanced pancreatic carcinoma. Cancer 1996;78:633–638.
    External Resources
  4. Storniolo AM, Enas MH, Brown CA, Voi M, Rothenberg ML, Schilsky R: An investigational new drug treatment program for patients with gemcitabine. Cancer 1999;85:1261–1268.
    External Resources
  5. Rothenberg ML, Abbruzzese JL, Moore M, Portenoy RK, Robertson JM, Wanebo HJ: A rationale for expanding the endpoints for clinical trials in advanced pancreatic carcinoma. Cancer 1996;78:627–632.
    External Resources
  6. Ahlgren JD: Chemotherapy for pancreatic carcinoma. Cancer 1996;78:654–63.
    External Resources
  7. Cascinu S, Silva RR, Barni S, Labianca R, Frontini L, Piazza E, Pancera G, Giordani P, Giuliodori L, Pessi MA, Fusco V, Luporini G, Cellerino R, Catalano G: A combination of gemcitabine and 5-fluorouracil in advanced pancreatic cancer, a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD). Br J Cancer 1999;80:1595–1598.
    External Resources
  8. Burris HA, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps C, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD, von Hoff DD: Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: A randomized trial. J Clin Oncol 1997;15:2403–2413.
    External Resources
  9. Rothenberg ML, Moore M, Cripps MC, Andersen JS, Portenoy RK, Burris III HA, Green MR, Tarassoff PG, Brown TD, Casper ES, Storniolo A-M, von Hoff DD: A phase II trial of gemcitabine in patients with 5-FU-refractory pancreas cancer. Ann Oncol 1996;7:347–353.
    External Resources
  10. Gattani AM, Mandeli J, Bruckner HW: Tumor markers in patients with pancreatic carcinoma. Cancer 1996;78:57–62.
    External Resources
  11. Glenn J, Steinberg WM, Kurtzman SH, Steinberg SM, Sindelar WF: Evaluation of the utility of a radioimmunoassay for serum CA 19-9 levels in patients before and after treatment of carcinoma of the pancreas. J Clin Oncol 1988;6:462–468.
    External Resources
  12. Lundin J, Roberts PJ, Kuusela P, Haglund C: The prognostic value of preoperative serum levels of CA 19-9 and CEA in patients with pancreatic cancer. Br J Cancer 1994;69:515–519.
    External Resources
  13. Willett CG, Daly WJ, Warshaw AL: CA 19-9 is an index of response to neoadjuvant chemoradiation therapy in pancreatic cancer. Am J Surg 1996;172: 350–352.
    External Resources
  14. Heinemann V, Schermuly MM, Stieber P, Schulz L, Jüngst D, Wilkowski R, Schalhorn A: CA 19-9: A predictor of response in pancreatic cancer treated with gemcitabine and cisplatin. Anticancer Res 1999;19:1–3.
    External Resources
  15. Rougier P, Ducreux M, Douillard JY, Seitz JF, Bugat R, Bosset JF, Merouche Y, Raoul JL, Ychou M, Adenis A, Cvitkovic Bertheau F, Luboinski M, Pignon JP: Efficacy of 5-FU + cisplatin (FUP) compared to bolus 5-FU (FU) in advanced pancreatic carcinoma (APC): A randomized trial from the French Anticancer Centers Digestive Group (FNLCCDG). Proc Am Soc Clin Oncol 1999;18:(abstract 1050).
  16. Cullinan S, Moertel CG, Wieand HS, Schutt AJ, Krook JE, Foley JF, Norris BN, Kardinal CG, Tschetter LK, Barlow JF: A phase III trial on the therapy of advanced pancreatic carcinoma. Cancer 1990;65:2207–2212.
    External Resources
  17. Heinemann V, Hertel LW, Grindey GB, Plunkett W: Comparison of the cellular pharmacokinetics and toxicity of 2′,2′-difluoro-2′-deoxycytidine and 1-β-D-arabinofuranosylcytosine. Cancer Res 1988;48:4024–4031.
    External Resources
  18. Carmichael J, Fink U, Russell RCG, Spittle M F, Harris A L, Spiessl G, Blatter J: Phase II study of gemcitabine in patients with advanced pancreatic cancer. Br J Cancer 1995;73:101–105.
  19. Casper ES, Green MR, Kelsen DP, Heelan RT, Brown TD, Flombaum CD, Trochanowski B, Tarassoff PG: Phase II trial of gemcitabine (2′,2′-difluorodeoxycytidine) in patients with adenocarcinoma of the pancreas. Invest New Drugs 1994;12:29–34.
    External Resources
  20. Fossella FV, Lippman SM, Shin DM, Tarassoff P, Calayag-Jung M, Perez-Soler R, Lee JS, Murphy WK, Glisson B, Rivera E, Hong WK: Maximum-tolerated dose defined for single-agent gemcitabine: A phase I dose-escalation study in chemotherapy-naive patients with advanced non-small-cell lung cancer. J Clin Oncol 1997;15:310–316.
    External Resources
  21. Pur HU, Kornek GV, Raderer M, Fiebiger W, Zickero G, Pidlich J, Greul R, Schneeweiss B, Depisch D, Scheithauer W: Phase II trial of high-dose gemcitabine in patients with metastatic pancreatic adenocarcinoma. Onkologie 1999;22(suppl 1):81.
  22. Tempero M, Plunkett W, Ruiz van Harperen V, Hainsworth J, Hochster H, Lenzi R, Abbruzzese J: Randomised phase II trial of dose intense gemcitabine by standard infusion vs. fixed dose rate in metastatic pancreatic adenocarcinoma. Proc Am Soc Clin Oncol 1999;18:273a (abstract 1048).
  23. Plunkett W, Huang P, Gandhi V: Preclinical characteristics of gemcitabine. Anticancer Drugs 1995;6:7–13.
  24. Bergman AM, Ruiz van Haperen VWT, Veerman G, Kuiper CM, Peters GJ: Synergistic interaction between cisplatin and gemcitabine in ovarian and colon cancer cell lines. Purine and Pyrimidine Metabolism in Man 1995;7:139–143.
  25. Shewach DS, Lawrence TS: Radiosensitization of human tumor cells by gemcitabine in vitro. Semin Oncol 1995;22(suppl 11):68–71.
  26. Wils JA, Kok T, Wagener D JTh, Selleslags J, Duez N: Activity of cisplatin in adenocarcinoma of the pancreas. Eur J Cancer 1993;29A:203–204.
  27. Heinemann V, Wilke H, Possinger K, Mergenthaler H-G, Clemens M, König HJ, Illiger HJ, Ohnmacht U, Arning M, Schalhorn A, Fink U: Gemcitabine and cisplatin in the treatment of advanced and metastatic pancreatic cancer. Final results of a phase II study. Proc Am Soc Clin Oncol 1999;18:274a (abstract 1052).
  28. Philip PA, Zalupski M, Vaitkevicius VK, Arlauskas P, Shields A: Phase II study of gemcitabine and cisplatin in advanced or metastatic pancreatic cancer. Proc Am Soc Clin Oncol 1999;18:274a (abstract 1053).
  29. Colucci G, Riccardi F, Giuliani F, Lopez M, Gebbia V, Uomo M, Biglietto Mcigolari S, Borsellino N, Paoletti G, Maiello E, Gebbia N: Randomized trial of gemcitabine (GEM) alone or with cisplatin (CDDP) in the treatment of advanced pancreatic cancer (APC): A phase II multicenter study of the Southern Italy Oncology Group. Proc Am Soc Clin Oncol 1999;18:250a (abstract 961).
  30. De Gusmao CBRA, Murad AM, Scalabrini-Neto AM: Phase II trial of the use of gemcitabine and 5-fluorouracil in the treatment of advanced pancreatic and biliary tract adenocarcinoma. Proc Am Soc Clin Oncol 1998;17:abstract 1116.
  31. Hidalgo M, Castellano D, Paz-Ares L, Gravalos C, Diaz-Puente M, Hitt R, Alonso S, Cortes-Funes H: Phase I–II study of gemcitabine and fluorouracil as a continuous infusion in patients with pancreatic cancer. J Clin Oncol 1999;17:585–592.
    External Resources
  32. Pastorelli D, Peddrazoli S, Sperti C, Vicario G, Scelzi E, Santarossa S, Sgarbossa G, Fosser V, Manente P: Phase II trial with gemcitabine (GEM) + 5-fluorouracil (5-FU) in advanced pancreatic cancer (APC). Proc Am Soc Clin Oncol 2000;19:abstract 1110.
  33. Schulman KL, Kindler HL, Lad TE, Reilly K, Mani S, Vokes EE: Phase II study of gemcitabine (G) and continuous intravenous infusion (CIV) 5-fluorouracil (5-FU) in advanced pancreatic cancer (PC): A University of Chicago phase II consortium study. Proc Am Soc Clin Oncol 2000;19:abstract 1126.
  34. Lencioni M, Falcone A, Masi G, Fioretto L, Meucci I, Di Marsico R, Pfanner E, Galli C, Bonifazi V, Mazzocchi B, Tognarini L, Conte P: Phase I-II study of gemcitabine in combination with 24 hours continuous infusion (CI) of 5-fluorouracil 5-FU) and L-leucovorin (LV) in patients (pts) with advanced pancreatic carcinoma. Proc Am Soc Clin Oncol 2000;19:abstract 1235.
  35. Louvet C, Hammel P, Andre T, Vanica R, Landi B, Balosso J, Cattan S, Fonck M, Flesch M, Colin P, Gruson T, de Gramont A: Multicenter phase II study in advanced pancreatic adenocarcinoma patients treated with a combination of leucovorin, 5-FU bolus and infusion, and gemcitabine (FOLFUGEM regimen). Proc Am Soc Clin Oncol 1999;18:abstract 1054.
  36. Riedel C, Wein A, Wehler M, Lampert S, Fischer B, Hohenberger W, Hahn E, Schneider T: High-dose 5-fluorouracil (FU) 24-hour-infusion with gemcitabine (GEM): Tolerable and efficient in palliative outpatient treatment of pancreatic cancer. Proc Am Soc Clin Oncol 2000;19:abstract 1248.
  37. Rodriguez-Lescure A, Carrato A, Massuti B, Garcia-Gomez J, Herrero J, Gallego J, Diaz-Fernandez N, Gonzalvez ML: Phase II study of gemcitabine (GEM) and weekly 48-hour continuous infusion (CI) high dose 5-fluorouracil (5-FU) in advanced exocrine pancreatic cancer (APC). Proc Am Soc Clin Oncol 1999;18:abstract 1145.
  38. Reni M, Passoni P, Villa E: Definitive results of a phase II trial PEF-G (cisplatin, epirubicin, 5-fluorouracil continuous infusion, gemcitabine) in stage IV pancreatic adenocarcinoma. Proc Am Soc Clin Oncol 2000;19:abstract 1019.
  39. Mousseau M, Rebischung C, Garnier C, Chirpaz E, Provencal J, Papillon E, Balosso J, Charlety D, Lemoigne A, Pasquier D, Schaerer R, Esterni J: Phase I/II study in advanced pancreatic adenocarcinoma (APA) and carcinoma of unknown primary (CUP): A combination of leucovorin (LV), 5-FU bolus and infusion, gemcitabine (GEM), and oxaliplatin (L.OHP) (FOLFU GEMOX Regimen). Proc Am Soc Clin Oncol 2000;19:abstract 913.
  40. Rocha Lima C, Savarese D, Bruchner H, Dudek A, Echardt J, Hainsworth J, Lester E, Compton L, Locker P, Elfring G, Miller L, Green M: Multicenter phase II trial of first-line irinotecan and gemcitabine (Irinogem) in patients with locally advanced or metastatic pancreatic cancer (PC). Proc Am Soc Clin Oncol 2000;19:263a (abstract 1023).
  41. Stathopoulos G, Rigatos G, Dimopoulos M, Kouroussis C, Panopoulos C, Giannakakis T, Tzanninis D, Georgoulias V: Front-line treatment of pancreatic carcinoma with gemcitabine (GMB) in combination with irinotecan (CPT-11): Preliminary results of a multicenter phase II study. Proc Am Soc Clin Oncol 2000;19:abstract 1260.
  42. Ridwelski K, Kettner E, Florschütz A, Klein U, Eichelmann K, Lippert H: Final results of a phase I study of weekly gemcitabine and docetaxel in pancreatic carcinoma and preliminary results of a phase II study. Proc Am Soc Clin Oncol 2000;abstract 1256.
  43. Jacobs AD, Otero H, Picozzi V Jr, Aboulafia DM, Weiden PL: A phase I/II study of gemcitabine (G) and docetaxel (D) in patients (pts) with unresectable pancreatic cancer. Proc Am Soc Clin Oncol 2000;19:288a (abstract 1032).
  44. Clark JW, Ryan DP, Kulke MH, Grossbard ML, Fuchs CS, Grossman SR, Morgan JA, Earle CC, Shivdasani R, Grenon N, Berg D, Mayer RJ: Phase II study of gemcitabine and docetaxel in patients with metastatic pancreatic cancer. Proc Am Soc Clin Oncol 2000;19:abstract 1238.
  45. Nelson AR, Fingleton B, Rothenberg ML, Matrisian LM: Matrix metalloproteinases: Biologic activity and clinical implications. J Clin Oncol 2000;18:1135–1149.
    External Resources
  46. Carmichael J, Ledermann JA, Woll PJ, Gulliford T, Russel RC: Phase IB study of concurrent administration of marimastat and gemcitabine in non-resectable pancreatic cancer. Proc Am Soc Clin Oncol 1998;17:232a (abstract 888).
  47. Rosemurgy A, Buckels J, Charnley R, Winston R, Steward W, Staddon A, Curtis L, Rugg T, Rasmussen H and the marimastat in pancreatic cancer study group: A randomized study comparing marimastat to gemcitabine as first line therapy in patients with non-resectable pancreatic cancer. Proc Am Soc Clin Oncol 1999;18:261a (abstract 1005).
  48. British Biotech plc: Results of marimastat study 128: Pancreatic cancer monotherapy trial. Release date, 2/15/99. At http://www.britbio.co.uk/news/news_index.htm.

Article / Publication Details

First-Page Preview
Abstract of Review

Published online: December 28, 2000
Issue release date: December 2000

Number of Print Pages: 11
Number of Figures: 0
Number of Tables: 7

ISSN: 0030-2414 (Print)
eISSN: 1423-0232 (Online)

For additional information: https://www.karger.com/OCL

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2001, Vol.60, No. 1

December 2000

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