Skip to main content

Advertisement

Log in

Fluorouracil-based Chemoradiation with Either Gemcitabine or Fluorouracil Chemotherapy after Resection of Pancreatic Adenocarcinoma: 5-Year Analysis of the U.S. Intergroup/RTOG 9704 Phase III Trial

  • Pancreatic Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

The impact of the addition of gemcitabine to 5-fluorouracil (5-FU) chemoradiation (CRT) on 5-year overall survival (OS) in resected pancreatic adenocarcinoma are presented with updated results of a phase III trial.

Methods

After resection of pancreatic adenocarcinoma, patients were randomized to pre- and post-CRT 5-FU versus pre- and post-CRT gemcitabine. 5-FU was provided continuously at 250 mg/m2/day, and gemcitabine was provided at 1000 mg/m2 weekly. Both were provided over 3 weeks before and 12 weeks after CRT. CRT was provided at 50.4 Gy with continuously provided 5-FU. The primary end point was survival for all patients and for patients with tumor of the pancreatic head.

Results

Four hundred fifty-one patients were eligible. Univariate analysis showed no difference in OS. Pancreatic head tumor patients (n = 388) had a median survival and 5-year OS of 20.5 months and 22% with gemcitabine versus 17.1 months and 18% with 5-FU. On multivariate analysis, patients on the gemcitabine arm with pancreatic head tumors experienced a trend toward improved OS (P = 0.08). First site of relapse local recurrence in 28% of patients versus distant relapse in 73%.

Conclusions

The sequencing of 5-FU CRT with gemcitabine as done in this trial is not associated with a statistically significant improvement in OS. Despite local recurrence being approximately half of that reported in previous adjuvant trials, distant disease relapse still occurs in ≥70% of patients. These findings serve as the basis for the recently activated EORTC/U.S. Intergroup RTOG 0848 phase III adjuvant trial evaluating the impact of CRT after completion of a full course of gemcitabine.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Oettle H, Post S, Neuhaus P, et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized trial. JAMA. 2007;297:267–77.

    Article  PubMed  CAS  Google Scholar 

  2. Neuhaus P, Riess H, Post S, et al. CONKO-001: final results of the randomized, prospective, multicenter phase III trial of adjuvant chemotherapy with gemcitabine versus observation in patients with resected pancreatic cancer (PC). J Clin Oncol. 2008;26(suppl LBA4504).

  3. Neoptolemos J, Buchler M, Stocken DD, et al. ESPAC-3(v2): a multicenter, international, open-label, randomized, controlled phase III trial of adjuvant 5-fluorouracil/folonic acid (5-FU/FA) versus gemcitabine (GEM) in patients with resected pancreatic ductal adenocarcinoma. J Clin Oncol. 2009;27(suppl 18).

  4. Regine WF, Winter K, Abrams RA, et al. Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA. 2008;299:1019–26.

    Article  PubMed  CAS  Google Scholar 

  5. Nicecki SS, Sarr MG, Colby, TV, et al. Long-term survival after resection for ductal adenocarcinoma of the pancreas. Is it really improving? Ann Surg. 1995; 221:59–66.

    Article  Google Scholar 

  6. Pirokowski RJ, Believernicht SW, Lawrence W Jr, et al. Pancreatic and periampullary carcinoma: experience with 200 patients over a 12-year period. Am J Surg. 1982;143:189–93.

    Article  Google Scholar 

  7. Gudjonsson B. Cancer of the pancreas: 50 years of surgery. Cancer. 1987;60:2284–303.

    Article  PubMed  CAS  Google Scholar 

  8. Tepper J, Nardi G, Suit H. Carcinoma of the pancreas. Review of MGH experience from 1963–1973. Analysis of surgical failure and its implications for radiation therapy. Cancer. 1976;37:1519–24.

    Article  PubMed  CAS  Google Scholar 

  9. Griffin JF, Smalley SR, Jewell W, et al. Patterns of failure after curative resection of pancreatic carcinoma. Cancer. 1990;66:56–61.

    Article  PubMed  CAS  Google Scholar 

  10. Kalser MH, Ellenberg SS. Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg. 1985;120:899–903.

    CAS  Google Scholar 

  11. Klinkenbijl JH, Jeekel J, Sahmoud T, et al. Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC Gastrointestinal Tract Cancer Cooperative Group. Ann Surg. 1999;230:776–82.

    Article  PubMed  CAS  Google Scholar 

  12. Corsini MM, Miller RC, Haddock MG, et al. Adjuvant radiotherapy and chemotherapy for pancreatic carcinoma: the Mayo Clinic experience (1975–2005). J Clin Oncol. 2008;26:3511–6.

    Article  PubMed  Google Scholar 

  13. Herman JM, Schwartz MJ, Hsu CC, et al. Analysis of fluorouracil based adjuvant chemotherapy and radiation after pancreaticoduodenectomy for ductal adenocarcinoma of the pancreas: results of a large prospectively collected database at the Johns Hopkins Hospital. J Clin Oncol. 2008;26:3503–10.

    Article  PubMed  Google Scholar 

  14. ID Fleming, JS Cooper, DE Henson, et al. (1997) Exocrine pancreas. In: American Joint Committee on Cancer manual for staging of cancer. 5th ed. Philadelphia, PA: Lippincott-Raven, p. 122–3.

  15. Regine WF. Postoperative adjuvant therapy: past, present, and future trial development. In: Evans DB, Pisters PWT, Abbruzzese JL, eds. Pancreatic cancer. New York: Springer; 2006. p. 235–42.

    Google Scholar 

  16. Zelen M. The randomization and stratification of patients to clinical trials. J Chronic Dis. 1974;27:365–75.

    Article  PubMed  CAS  Google Scholar 

  17. Montgomery RC, Hoffman JP, Riley LB, et al. Prediction of recurrence and survival by post-resection CA19-9 values in patients with adenocarcinoma of the pancreas. Ann Surg Oncol. 1958;4:551–6.

    Article  Google Scholar 

  18. Kaplan EL, Meier P. Nonparameteric estimation from incomplete observations. J Am Stat Assoc. 1958;53(282):457–81.

    Article  Google Scholar 

  19. Mantel N. (1966) Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother. Rep 50:163–70.

    CAS  Google Scholar 

  20. Cox DR. Regression models and life tables. J Royal Stat Soc Ser B. 1972; 34:187–229.

    Google Scholar 

  21. Yeo CJ, Abrams RA, Grochow LB, et al. Pancreaticduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience. Ann Surg. 1997;225:621–36.

    Article  PubMed  CAS  Google Scholar 

  22. Benson A. Adjuvant therapy for pancreatic cancer. JAMA. 2007;297:311–3.

    Article  PubMed  CAS  Google Scholar 

  23. Neoptolemos JP, Stocken DD, Friess H, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004;350:1200–10.

    Article  PubMed  CAS  Google Scholar 

  24. Moore MJ, Goldstin D, Hamm, et al. Erlotinib Plus Gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007;25:1960–6.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

Supported by RTOG U10 CA21661 and CCOP U10 CA37422 grants from the NCI.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to William F. Regine MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Regine, W.F., Winter, K.A., Abrams, R. et al. Fluorouracil-based Chemoradiation with Either Gemcitabine or Fluorouracil Chemotherapy after Resection of Pancreatic Adenocarcinoma: 5-Year Analysis of the U.S. Intergroup/RTOG 9704 Phase III Trial. Ann Surg Oncol 18, 1319–1326 (2011). https://doi.org/10.1245/s10434-011-1630-6

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-011-1630-6

Keywords

Navigation