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Cancer Chemotherapy and Pharmacology

, Volume 61, Issue 1, pp 167–175 | Cite as

The gemcitabine, docetaxel, and capecitabine (GTX) regimen for metastatic pancreatic cancer: a retrospective analysis

  • Robert L. Fine
  • David R. Fogelman
  • Stephen M. Schreibman
  • Manisha Desai
  • William Sherman
  • James Strauss
  • Susan Guba
  • Riolan Andrade
  • John Chabot
Clinical Trial Report

Abstract

Purpose

We developed a laboratory based regimen called GTX which induces synergistic apoptosis in human pancreatic cancer cells. This retrospective review summarizes our clinical experience with GTX in an initial group of 35 patients; 66% untreated and 34% failed prior therapies.

Methods

All patients treated with GTX for metastatic pancreatic cancer, prior to initiation of a prospective phase II trial of GTX were assessed and followed until death. GTX consisted of capecitabine (X), 750 mg/m2 p.o. BID on days 1–14, gemcitabine (G) (750 mg/m2) over 75 min and docetaxel (T) (30 mg/m2) on days 4 and 11. Thus one cycle of GTX was 14 days with 7 days off for a 21 day cycle. Tumor assessments were repeated every 3 cycles.

Results

All 35 patients had metastatic pancreatic cancer (94% liver, 6% lung sites). Grade 3–4 hematological toxicities were: leukopenia and thrombocytopenia—both 14%, and anemia 9%, respectively. The overall response rate of all 35 patients treated with GTX (from 0.5 cycles onward) was 29% (CR/PR) by WHO criteria, and 31% had a minor response or stable disease (MR, SD). At the metastatic sites for the 35 patients, there were 9% complete (CR) and 31% partial (PR) responses (total 40%). For the 31 patients who had their primary tumor (4 patients had a prior Whipple resection), there were 13% CR and 19% PR for a response rate of 32% at the primary tumor site. Overall median progression free survival of responders was 6.3 months (95% C.I. 4.4–10.4 months) and median survival was 11.2 months (95% C.I. 8.1–15.1 months). Survival after initiation of GTX at 12, 18, 24 and 30 months was 43, 29, 20, and 11%, respectively.

Conclusion

Our retrospective review suggests that GTX has potential as a regimen for untreated and treated metastatic pancreatic cancer.

Keywords

Pancreatic Cancer Docetaxel Gemcitabine Capecitabine Erlotinib 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

We wish to thank the Marcove and Manelski Family Foundations, Susan Grant Kaplansky Memorial Fund and the Herbert Irving Scholar Award for support of these clinical and laboratory studies to RLF. The clinical expertise of our Data Collector, Cara DeRosa, and Research Nurse, Kyung Chu, was invaluable to this report. We also thank Susan Bronson and Gina Egan for their excellent assistance in the preparation of this manuscript. This paper is dedicated to the memory and courage of Denis Manelski who was one of the first patients to receive GTX and lived 3 years with metastatic (liver) pancreatic cancer.

References

  1. 1.
    Jemal A, Murray T, Samuels A (2003) Cancer statistics, 2003. CA-Cancer J Clin 53:5–26PubMedCrossRefGoogle Scholar
  2. 2.
    Burris HA, Moore MJ, Anderson J et al (1997) Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Onc 15(6):2403–2413Google Scholar
  3. 3.
    Brand R, Capadano M, Tempero M (1997) A phase I trial of weekly gemcitabine administered as a prolonged infusion in patients with pancreatic cancer and other solid tumors. Invest New Drugs 15(4):331–341PubMedCrossRefGoogle Scholar
  4. 4.
    Tempero M, Plunkett W, Ruiz Van Haperen V, Hainsworth J, Hochster H, Lenzi R, Abbruzzese J (2003) Randomized phase II comparison of dose-intense gemcitabine: thirty-minute infusion and fixed dose rate infusion in patients with pancreatic adenocarcinoma. J Clin Onc 21(18):3402–3408CrossRefGoogle Scholar
  5. 5.
    Moore M, Goldstein D, Hamm J et al (2005) Erlotinib plus gemcitabine compared to gemcitabine alone in patients with advanced pancreatic cancer. A phase III trial of the National Cancer Institute of Canada Clinical Trials Group [NCIC-CTG]. J Clin Oncol 23:1s, (Suppl, Abstr 1)Google Scholar
  6. 6.
    Cunningham D, Chau I, Stocken D, Barletta E, Moscetti L, Recchia F et al Phase III randomised comparison of gemcitabine (GEM) versus gemcitabine plus capecitabine (GEM-CAP) in patients with advanced pancreatic cancer. Eur J Cancer Suppl 4, Abstr. PS 11Google Scholar
  7. 7.
    Fine RL, Fogelman DR, Sherman W et al (2003) The GTX regimen: A biochemically synergistic combination for advanced pancreatic cancer (PC). Proc Am Soc Clin Onc Abstr #1129Google Scholar
  8. 8.
    Fine RL, Fogelman DR, Schreibman S, Guba S, Sharma J, Shapiro G (2004) GTX chemotherapy for metastatic pancreatic cancer: Response, survival, and toxicity data. J Clin Oncol 22:381s suppl. Abstr #4271Google Scholar
  9. 9.
    Sherman WH, Fine RL (2001) Combination gemcitabine and docetaxel in advanced adenocarcinoma of the pancreas. Oncology 60(4):316–321PubMedCrossRefGoogle Scholar
  10. 10.
    Hess V, Salzberg M, Borner M et al (2003) Combining capecitabine and gemcitabine in patients with advanced pancreatic carcinoma: A phase I/II trial. J Clin Oncol 21(1):66–68PubMedCrossRefGoogle Scholar
  11. 11.
    Fogelman DR, Sherman W, Schreibman S, Fine RL (2003) Effective salvage chemotherapy with minimal toxicity for relapsed, advanced pancreatic cancer. Proc Am Soc Clin Onc Abstr #1517Google Scholar
  12. 12.
    Fogelman D, Fine RL, Schreibman S (2004) Effective salvage therapy (T-GX) for pancreatic cancer patients after chemotherapy with GTX. J Clin Oncol 22:380s suppl. Abstr #4268Google Scholar
  13. 13.
    Khorana A, Fine RL (2004) Pancreatic cancer and thromboembolic disease. Lancet Oncol 5(11):655–663PubMedCrossRefGoogle Scholar
  14. 14.
    Poplin E, Levy D, Berlin J et al (2006) Phase III trial of gemcitabine (30-minute infusion) versus gemcitabine (fixed-dose-rate infusion [FDR]) versus gemcitabine + oxaliplatin(GEMOX) in patients with advanced pancreatic cancer (E6201). J Clin Oncol 24(18):2006, LBA 4004Google Scholar
  15. 15.
    Cartwright TH, Cohn A, Varkey JA et al (2002) Phase II study of oral capecitabine in patients with advanced or metastatic pancreatic cancer. J Clin Oncol 20(1):160–164PubMedCrossRefGoogle Scholar
  16. 16.
    Stathopoulos GP, Syrigos K, Polyzos A et al (2004) Front-line treatment of inoperable or metastatic pancreatic cancer with gemcitabine and capecitabine: an intergroup, multicenter, phase II study. Ann Oncol 15:224–229PubMedCrossRefGoogle Scholar
  17. 17.
    Hermann R, Bodoky G, Ruhstaller T et al (2005) Gemcitabine (G) plus capecitabine versus G alone in advanced/metastatic pancreatic cancer. A randomized phase III study of the SAKK and CECOG groups, Proc Am Soc Clin Oncol Abst #4010Google Scholar
  18. 18.
    Rougier P, Adenis A, Dureux M et al (2000) A phase II study: Docetaxel as first line chemotherapy for advanced pancreatic adenocarcinoma. Eur J Cancer 36:1016–1025PubMedCrossRefGoogle Scholar
  19. 19.
    Androulakis N, Kourousis C, Dimopoulos M (1999) Treatment of pancreatic cancer with docetaxel and granulocyte colony-stimulating factor: a multicenter phase II trial. J Clin Oncol 17:1779–1785PubMedGoogle Scholar
  20. 20.
    Schneider BP, Ganjoo KN, Seitz DE et al (2003) Phase II study of gemcitabine plus docetaxel in advanced pancreatic cancer: a Hoosier Oncology Group study. Oncology 65(3):218–223PubMedCrossRefGoogle Scholar
  21. 21.
    Louvet C et al (2004) Gemcitabine versus GEMOX (gemcitabine + oxaliplatin) in non resectable pancreatic adenocarcinoma : Final results of the GERCOR /GISCAD Intergroup Phase III. J Clin Oncol 22:315s suppl, abstr #4008Google Scholar
  22. 22.
    Heineman V, Quietzsch D, Gieseler F (2003) A phase III trial comparing gemcitabine plus cisplatin vs. gemcitabine alone in advanced pancreatic carcinoma, Proc Am Soc Clin Oncol Abst #1003Google Scholar
  23. 23.
    Rocha Lima CM, Rotche R, Jeffrey M et al (2003) A randomized phase 3 study comparing efficacy and safety of gemcitabine (GEM) and irinotecan (I), to GEM alone in patients (pts) with locally advanced or metastatic pancreatic cancer who have not received prior systemic therapy. Proc Am Soc Clin Onc Abst #1005Google Scholar
  24. 24.
    Kozuch P, Grossbard ML, Barzdins A et al (2001) Irinotecan Combined with gemcitabine, 5-fluorouracil, leucovorin, and cisplatin (G-FLIP) is an effective and noncrossresistant treatment for chemotherapy refractory pancreatic cancer. Oncologist 6(6):488–495PubMedCrossRefGoogle Scholar
  25. 25.
    El-Rayes BF, Zalupski MM, Shields AF et al (2003) Phase II study of gemcitabine, cisplatin, and infusional fluorouracil in advanced pancreatic cancer. J Clin Oncol 15(1):2920–2925CrossRefGoogle Scholar
  26. 26.
    Araneo M, Bruckner HW, Grossbard ML et al (2003) Biweekly low-dose sequential gemcitabine, 5-fluorouracil, leucovorin and cisplatin (GFP): A highly active novel therapy for metastatic adenocarcinoma of the exocrine pancreas. Cancer Invest 21(4):489–496PubMedCrossRefGoogle Scholar
  27. 27.
  28. 28.
    Kindler HL, Bylow KA, Hochster HS et al (2006) A randomized phase III study of bevacizumab (B) and gemcitabine (G) plus cetuximab (C) or erlotinib (E) in patients (pts) with advanced pancreatic cancer (PC): a preliminary analysis. J Clin Onc 24(18S):A4040Google Scholar
  29. 29.
    Berlin JD, Adak S, Vaughn DJ et al (2000) A phase II study of gemcitabine and 5-fluorouracil in metastatic pancreatic cancer: an Eastern Cooperative Oncology Group study (E3296). Oncology 58:215–218PubMedCrossRefGoogle Scholar
  30. 30.
    Berlin JD, Catalano P, Thomas J et al (2002) Phase III study of gemcitabine with fluorouracil versus gemcitabine alone in patients with advanced pancreatic carcinoma: Eastern Cooperative Oncology Group Trial E2297. J Clin Oncol 20:3270–3275PubMedCrossRefGoogle Scholar
  31. 31.
    Reiss H, Helm A, Niedergethmann M et al (2005) Randomized, prospective multicenter phase III trial of gemcitabine, 5FU, folinic acid versus gemcitabine alone in patients with advanced pancreatic cancer. Proc Am Soc Clin Oncol Abst #4009Google Scholar
  32. 32.
    Hidalgo M, Castellano D, Paz-Ares L et al (1999) Phase I-II study of gemcitabine and fluorouracil as a continuous infusion in patients with pancreatic cancer. J Clin Oncol 17(2):585–592PubMedGoogle Scholar
  33. 33.
    Fine RL, Fogelman DR, Sherman W et al (2006) Gemcitabine, Docetaxel, and Capecitabine (GTX) in the treatment of metastatic pancreatic cancer (PC): A prospective phase II Study. Proc Am Soc Clin Oncol Abst #14024Google Scholar
  34. 34.
    Sawada N, Ishikawa T, Fukase Y et al (1998) Induction of thymidine phosphorylase activity and enhancement of capecitabine efficacy by taxol/docetaxel in human cancer xenografts. Clin Cancer Res Suppl 4(4):1013–1019Google Scholar
  35. 35.
    Fogelman DR, Chen J, Chabot J, Allendorf J, Schreibman S, Ennis R, Fine RL (2004) The evolution of adjuvant and neoadjuvant chemotherapy and radiation for advanced pancreatic cancer: From 5-FU to GTX. Surg Oncol Clin No Am 13:711–735CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Robert L. Fine
    • 1
    • 8
  • David R. Fogelman
    • 1
  • Stephen M. Schreibman
    • 2
  • Manisha Desai
    • 3
  • William Sherman
    • 1
  • James Strauss
    • 4
  • Susan Guba
    • 5
  • Riolan Andrade
    • 6
  • John Chabot
    • 7
  1. 1.Experimental Therapeutics Program, Division of Medical Oncology, Department of MedicineNew York Presbyterian Medical Center, Columbia University College of Physicians and Surgeons, and The Pancreas Center at ColumbiaNew YorkUSA
  2. 2.Oncology and Hematology SpecialistsMorristown Memorial HospitalMorristownUSA
  3. 3.Department of Biostatistics, Mailman School of Public HealthNew York Presbyterian Medical Center, Columbia University College of Physicians and Surgeons, and The Pancreas Center at ColumbiaNew YorkUSA
  4. 4.U.S. Oncology AssociatesDallasUSA
  5. 5.Texas Cancer AssociatesDallasUSA
  6. 6.Hematology-Oncology AssociatesPoughkeepsieUSA
  7. 7.Whipple Service, Department of SurgeryNew York Presbyterian Medical Center, Columbia University College of Physicians and Surgeons, and The Pancreas Center at ColumbiaNew YorkUSA
  8. 8.Division of Medical OncologyColumbia University Medical CenterNew YorkUSA

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