Cancer Chemotherapy and Pharmacology

, Volume 64, Issue 6, pp 1253–1259 | Cite as

Outcome of upfront combination chemotherapy followed by chemoradiation for locally advanced pancreatic adenocarcinoma

  • Michele Reni
  • S. Cereda
  • G. Balzano
  • P. Passoni
  • A. Rognone
  • A. Zerbi
  • R. Nicoletti
  • E. Mazza
  • P. G. Arcidiacono
  • V. Di Carlo
  • E. Villa
Original Article



The role and timing of chemotherapy and radiation for treating stage III pancreatic adenocarcinoma remains controversial.


Treatment-naive patients with stage III non-resectable pancreatic adenocarcinoma were treated with PEFG/PEXG (cisplatin, epirubicin, 5-fluorouracil (F)/capecitabine (X), gemcitabine) or PDXG (docetaxel substituting epirubicin) regimen for 6 months followed by radiotherapy (50–60 Gy) with concurrent F or X or G.


Ninety-one patients were registered between April 1997 and December 2007. Forty-three patients (47%) had a partial remission and 38 (42%) had a stable disease. Thirteen patients (14%) were radically resected yielding one pathologic complete remission. Median survival (OS) was 16.2 months. Median progression-free survival was 9.9 months. Pattern of failure consisted of isolated local failure (N = 26, 35%); both local and systemic failure (N = 14, 19%); isolated systemic failure (N = 35, 47%).


Combination chemotherapy with four-drug regimens followed by chemoradiation was a feasible strategy showing relevant results in stage III pancreatic adenocarcinoma.


Locally advanced pancreatic cancer Chemotherapy Stage III pancreatic cancer Radiotherapy Pancreatic cancer 


  1. 1.
    Neoptolemos JP, Stocken DD, Friess H et al (2004) A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 350:1200–1210PubMedCrossRefGoogle Scholar
  2. 2.
    Oettle H, Post S, Neuhaus P et al (2007) Adjuvant chemotherapy with Gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer. A randomized controlled trial. JAMA 297:267–277PubMedCrossRefGoogle Scholar
  3. 3.
    Sobin LH, Wittekind CH (eds) (2002) Exocrine pancreas. In: AJCC cancer staging manual, 6th edn. Springer, New York, p 157Google Scholar
  4. 4.
    Moertel C, Childs D, Reitmeier R, Colby MY Jr, Holbrook MA (1969) Combined 5FU and supervoltage RT for locally unresectable GI cancer. Lancet 2:865–867PubMedCrossRefGoogle Scholar
  5. 5.
    Moertel CG, Frytak S, Hahn RG et al (1981) Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group. Cancer 48:1705–1710PubMedCrossRefGoogle Scholar
  6. 6.
    Klaassen DJ, MacIntyre JM, Catton GE et al (1985) Treatment of locally unresectable cancer of the stomach and pancreas: a randomized comparison of 5-fluorouracil alone with radiation plus concurrent and maintenance 5-fluorouracil—An Eastern Cooperative Oncology Group study. J Clin Oncol 3:373–378PubMedGoogle Scholar
  7. 7.
    Gastrointestinal Tumor Study Group (1988) Treatment of locally unresectable carcinoma of the pancreas: comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone. J Natl Cancer Inst 80:751–755CrossRefGoogle Scholar
  8. 8.
    Loehrer PJ Sr, Powell ME, Cardenes HR, Wagner L, Brell M, Ramanathan RK, Crane CH, Alberts SR, Benson III AB (2008) A randomised phase III study of gemcitabine in combination with radiation therapy versus gemcitabine alone in patients with localized, unresectable pancreatic cancer:E4201. Proc Am Soc Clin Oncol 26, OP 4506Google Scholar
  9. 9.
    Chauffert B, Mornex F, Bonnetain F et al (2008) Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer. Definitive results of the 2000_01 FFCD/SFRO study. Ann Oncol 19(9):1592–1599Google Scholar
  10. 10.
    Sultana A, Tudur Smith C, Cunningham D, Starling N, Tait D, Neoptolemos JP, Ghaneh P (2007) Systematic review, including meta-analyses, on the management of locally advanced pancreatic cancer using radiation/combined modality therapy. Br J Cancer 96(8):1183–1190PubMedCrossRefGoogle Scholar
  11. 11.
    Huguet F, Andre′ T, Hammel P et al (2007) Impact of chemoradiotherapy after disease control with chemotherapy in locally advanced pancreatic adenocarcinoma in GERCOR Phase II and III Studies. J Clin Oncol 20:326–331CrossRefGoogle Scholar
  12. 12.
    Reni M, Passoni P, Panucci MG, Nicoletti R, Galli L, Balzano G, Zerbi A, Di Carlo V, Villa E (2001) Definitive results of a phase ii trial of PEF-G (cisplatin, epirubicin, 5-fluorouracil continuous infusion, gemcitabine) in stage IV pancreatic adenocarcinoma. J Clin Oncol 19:2679–2686PubMedGoogle Scholar
  13. 13.
    Reni M, Cordio S, Milandri C, Passoni P, Bonetto E, Oliani C, Luppi G, Nicoletti R, Galli L, Bordonaro R, Passardi A, Zerbi A, Balzano G, Aldrighetti L, Staudacher C, Villa E, Di Carlo V (2005) Gemcitabine versus cisplatin, epirubicin, 5-fluorouracil, gemcitabine in advanced pancreatic cancer: a randomised controlled multicentre phase III trial. Lancet Oncol 6:369–376PubMedCrossRefGoogle Scholar
  14. 14.
    Reni M, Cereda S, Bonetto E et al (2007) Dose-intense PEFG (cisplatin, epirubicin, 5-fluorouracil, gemcitabine) in advanced pancreatic adenocarcinoma: a dose-finding study. Cancer Invest 25:594–598CrossRefGoogle Scholar
  15. 15.
    Reni M, Cereda S, Bonetto E, Viganò MG, Passoni P, Zerbi A, Balzano G, Nicoletti R, Staudacher C, Di Carlo V (2007) Dose-intense PEFG (cisplatin, epirubicin, 5-fluorouracil, gemcitabine) in advanced pancreatic adenocarcinoma. Cancer Chemother Pharmacol 59:361–367PubMedCrossRefGoogle Scholar
  16. 16.
    Reni M, Cereda S, Passoni P, Rognone A, Mazza E, Nicoletti R, Arcidiacono P, Zerbi A, Balzano G, Di Carlo V (2007) A randomized phase II trial of PEXG (cisplatin, epirubicin, capecitabine, gemcitabine) or PDXG (docetaxel) regimen in advanced pancreatic adenocarcinoma. Proc Am Soc Clin Oncol 25 (abstract 4628)Google Scholar
  17. 17.
    Therasse P, Arbuck SG, Eisenhaur EA, Wanders J, Kaplan RS, Rubinstein L et al (2004) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92(3):205–216Google Scholar
  18. 18.
    Ajani JA, Welch SR, Raber MN, Fields WS, Krakoff IH (1990) Comprehensive criteria for assessing therapy-induced toxicity. Cancer Invest 8:147–159PubMedCrossRefGoogle Scholar
  19. 19.
    Reni M, Cereda S, Balzano G, Passoni P, Rognone A, Ceraulo D, Fugazza C, Mazza E, Zerbi A, Di Carlo V, Villa E (2009) Carbohydrate antigen (CA)19-9 change during chemotherapy for advanced pancreatic adenocarcinoma. Cancer (in press)Google Scholar
  20. 20.
    Haddock MG, Swaminathan R, Foster NR, Hauge MD, Martenson JA, Camoriano JK, Stella PJ, Tenglin RC, Schaefer PL, Moore DF Jr, Alberts SR (2007) Gemcitabine, cisplatin, and radiotherapy for patients with locally advanced pancreatic adenocarcinoma: results of the North Central Cancer Treatment Group Phase II Study N9942. J Clin Oncol 25(18):2567–2572PubMedCrossRefGoogle Scholar
  21. 21.
    Ko AH, Quivey JM, Venook AP, Bergsland EK, Dito E, Schillinger B, Tempero MA (2007) A phase II study of fixed-dose rate gemcitabine plus low-dose cisplatin followed by consolidative chemoradiation for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 68(3):809–816PubMedGoogle Scholar
  22. 22.
    Brade A, Brierley J, Oza A, Gallinger S, Cummings B, Maclean M, Pond GR, Hedley D, Wong S, Townsley C, Brezden-Masley C, Moore M (2007) Concurrent gemcitabine and radiotherapy with and without neoadjuvant gemcitabine for locally advanced unresectable or resected pancreatic cancer: a phase I–II study. Int J Radiat Oncol Biol Phys 67(4):1027–1036PubMedGoogle Scholar
  23. 23.
    Magnino A, Gatti M, Massucco P, Sperti E, Faggiuolo R, Regge D, Capussotti L, Gabriele P, Aglietta M (2005) Phase II trial of primary radiation therapy and concurrent chemotherapy for patients with locally advanced pancreatic cancer. Oncology 68(4–6):493–499PubMedCrossRefGoogle Scholar
  24. 24.
    Crane CH, Ellis LM, Abbruzzese JL, Amos C, Xiong HQ, Ho L, Evans DB, Tamm EP, Ng C, Pisters PWT, Charnsangavej C, Delclos ME, O’Reilly M, Lee JE, Wolff RA (2006) Phase I trial evaluating the safety of bevacizumab with concurrent radiotherapy and capecitabine in locally advanced pancreatic cancer. J Clin Oncol 24:1145–1151PubMedCrossRefGoogle Scholar
  25. 25.
    Marti JL, Hochster HS, Hiotis SP, Donahue B, Ryan T, Newman E (2008) Phase I/II trial of induction chemotherapy followed by concurrent chemoradiotherapy and surgery for locoregionally advanced pancreatic cancer. Ann Oncol 15(12):3521–3531CrossRefGoogle Scholar
  26. 26.
    Moureau-Zabotto L, Phelip J-M, Afchain P, Mineur L, André T, Vendrely V, Lledo G, Dupuis O, Huguet F, Touboul E, Balosso J, Louvet C (2008) Concomitant administration of weekly oxaliplatin, fluorouracil continuous infusion, and radiotherapy after 2 months of gemcitabine and oxaliplatin induction in patients with locally advanced pancreatic cancer: a Groupe Coordinateur Multidisciplinaire en Oncologie phase II study. J Clin Oncol 26:1080–1085PubMedCrossRefGoogle Scholar
  27. 27.
    Balzano G, Zerbi A, Capretti G, Rocchetti S, Capitanio V, Di Carlo V (2008) Effect of hospital volume on outcome of pancreaticoduodenectomy in Italy. Br J Surg 95:357–362PubMedCrossRefGoogle Scholar
  28. 28.
    Sohn TA, Lillemoe KD, Cameron JL et al (1999) Reexploration for periampullary carcinoma: resectability, perioperative results, pathology, and long-term outcome. Ann Surg 229:393–400PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Michele Reni
    • 1
  • S. Cereda
    • 1
  • G. Balzano
    • 2
  • P. Passoni
    • 3
  • A. Rognone
    • 1
  • A. Zerbi
    • 2
  • R. Nicoletti
    • 4
  • E. Mazza
    • 1
  • P. G. Arcidiacono
    • 5
  • V. Di Carlo
    • 2
  • E. Villa
    • 1
  1. 1.Department of OncologyS. Raffaele Scientific InstituteMilanItaly
  2. 2.Department of SurgeryS. Raffaele Scientific InstituteMilanItaly
  3. 3.Department of RadiotherapyS. Raffaele Scientific InstituteMilanItaly
  4. 4.Department of RadiologyS. Raffaele Scientific InstituteMilanItaly
  5. 5.Department of GastroenterologyS. Raffaele Scientific InstituteMilanItaly

Personalised recommendations