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Open Access 01-12-2018 | Study protocol

Resectable pancreatic adenocarcinoma neo-adjuvant FOLF(IRIN)OX-based chemotherapy - a multicenter, non-comparative, randomized, phase II trial (PANACHE01-PRODIGE48 study)

Authors: Lilian Schwarz, Dewi Vernerey, Jean-Baptiste Bachet, Jean-Jacques Tuech, Fabienne Portales, Pierre Michel, Antonio Sa Cunha

Published in: BMC Cancer | Issue 1/2018

Abstract

Background

At time of diagnosis, less than 10% of patients with pancreatic adenocarcinomas (PDAC) are considered to be immediately operable (i.e. resectable). Considering their poor overall survival (OS), only tumours without vascular invasion (NCCN 2017) should be considered for resection, i.e. those for which resection with disease-free margins (R0) is theoretically possible in absence of presurgery treatment. With regard to high R1 rates and undetectable locoregional and/or metastatic spreading prior to surgery explain (at least in part) the observed 1-year relapse and mortality rates of 50 and 25%, respectively. Today, upfront surgery followed by adjuvant chemotherapy is the reference treatment in Europe. The main limitation of the adjuvant approach is the low rate of completion of the full therapeutic sequence. Indeed, only 47 to 60% patients received any adjuvant therapy after resection compared to more than 75% for neoadjuvant therapy. No previous prospective study has compared this approach to a neoadjuvant FOLFIRINOX or FOLFOX chemotherapy for resectable PDAC.

Methods

PANACHE01-PRODIGE48 is a prospective multicentre controlled randomized non comparative Phase II trial, evaluating the safety and efficacy of two regimens of neo-adjuvant chemotherapy (4 cycles of mFOLFIRINOX or FOLFOX) relative to the current reference treatment (surgery and then adjuvant chemotherapy) in patients with resectable PDAC. The main co-primary endpoints are OS rate at 12 months and the rate of patients undergoing the full therapeutic sequence.

Discussion

The “ideal” cancer treatment for resectable PDAC would have the following characteristics: administration to the highest possible proportion of patients, ability to identify fast-progressing patients (i.e. poor candidates for surgery), a low rate of R1 resections (through optimisation of local disease control), and an acceptable toxicity profile. The neoadjuvant approach may meet all these criteria. With respect to published data on the efficacy of FOLFOX and mFOLFIRINOX, these two regimens are potential candidates for neoadjuvant use in the aim to optimising oncological outcomes in resectable PDAC.

Trial registration

ClinicalTrials.gov, NCT02959879. Trial registration date: November 9, 2016.

Carpelan-Holmstrom M, Nordling S, Pukkala E, et al. Does anyone survive pancreatic ductal adenocarcinoma? A nationwide study re-evaluating the data of the Finnish Cancer registry. Gut. 2005;54:385–7.PubMedPubMedCentral

Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–49.PubMed

Guerin S, Hill C. Cancer epidemiology in France in 2010, comparison with the USA. Bulletin du cancer. 2010;97:47–54.PubMed

Simard EP, Ward EM, Siegel R, et al. Cancers with increasing incidence trends in the United States: 1999 through 2008. CA Cancer J Clin. 2012;

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 controlled trial. JAMA. 2007;297:267–77.PubMed

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.PubMed

Neoptolemos JP, Stocken DD, Bassi C, et al. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA. 2010;304:1073–81.PubMed

Murakami Y, Uemura K, Sudo T, et al. Number of metastatic lymph nodes, but not lymph node ratio, is an independent prognostic factor after resection of pancreatic carcinoma. J Am Coll Surg. 2010;211:196–204.PubMed

Tempero MA, Malafa MP, Al-Hawary M, et al. Pancreatic adenocarcinoma, version 2.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2017;15:1028–61.

10.

Verbeke CS, Smith AM. Survival after pancreaticoduodenectomy is not improved by extending resections to achieve negative margins. Ann Surg. 2010;251:776–7. author reply 777–778PubMed

11.

Esposito I, Kleeff J, Bergmann F, et al. Most pancreatic cancer resections are R1 resections. Ann Surg Oncol. 2008;15:1651–60.PubMed

12.

Delpero JR, Bachellier P, Regenet N, et al. Pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: a French multicentre prospective evaluation of resection margins in 150 evaluable specimens. HPB (Oxford). 2014;16:20-33PubMed

13.

Ghaneh P, Kleeff J, Halloran CM, et al. The impact of positive resection margins on survival and recurrence following resection and adjuvant chemotherapy for pancreatic ductal adenocarcinoma. Ann Surg. 2017. [Epub ahead of print].

14.

Neoptolemos JP, Palmer DH, Ghaneh P, et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised. phase 3 trial Lancet. 2017;389:1011–24.PubMed

15.

DeOliveira ML, Winter JM, Schafer M, et al. Assessment of complications after pancreatic surgery: a novel grading system applied to 633 patients undergoing pancreaticoduodenectomy. Ann Surg. 2006;244:931–7. discussion 937–939PubMedPubMedCentral

16.

Gouma DJ, van Geenen RC, van Gulik TM, et al. Rates of complications and death after pancreaticoduodenectomy: risk factors and the impact of hospital volume. Ann Surg. 2000;232:786–95.PubMedPubMedCentral

17.

Le Page S, Caputo S, Kwiatkowski F, Berard P, Gouillat C. Séquelles fonctionnelles et qualité de vie après duodénopancréatectomie céphalique. J de chirurgie. 2008;145:32–6.

18.

Regine WF, Winter KA, 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.PubMed

19.

Oettle H, Neuhaus P, Hochhaus A, et al. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013;310:1473–81.PubMed

20.

Gillen S, Schuster T, Meyer Zum Buschenfelde C, et al. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med. 2010;7:e1000267.PubMedPubMedCentral

21.

Tzeng CW, Tran Cao HS, Lee JE, et al. Treatment sequencing for resectable pancreatic cancer: influence of early metastases and surgical complications on multimodality therapy completion and survival. J Gastrointest Surg. 2014;18:16–24. discussion 24–15PubMed

22.

Merkow RP, Bilimoria KY, Tomlinson JS, et al. Postoperative complications reduce adjuvant chemotherapy use in Resectable pancreatic Cancer. Ann Surg. 2014;260:372-7.PubMed

23.

Valle JW, Palmer D, Jackson R, et al. Optimal duration and timing of adjuvant chemotherapy after definitive surgery for ductal adenocarcinoma of the pancreas: ongoing lessons from the ESPAC-3 study. J Clin Oncol. 2014;32:504–12.PubMed

24.

Ueno H, Kosuge T, Matsuyama Y, et al. A randomised phase III trial comparing gemcitabine with surgery-only in patients with resected pancreatic cancer: Japanese study Group of Adjuvant Therapy for pancreatic Cancer. Br J Cancer. 2009;101:908–15.PubMedPubMedCentral

25.

Hoffman JP, Lipsitz S, Pisansky T, et al. Phase II trial of preoperative radiation therapy and chemotherapy for patients with localized, resectable adenocarcinoma of the pancreas: an Eastern Cooperative Oncology Group Study. J Clin Oncol. 1998;16:317–23.PubMed

26.

Motoi F, Ishida K, Fujishima F, et al. Neoadjuvant chemotherapy with gemcitabine and S-1 for Resectable and borderline pancreatic ductal adenocarcinoma: results from a prospective multi-institutional phase 2 trial. Ann Surg Oncol. 2013;20(12):3794–801.PubMed

27.

Takahashi H, Ohigashi H, Gotoh K, et al. Preoperative gemcitabine-based Chemoradiation therapy for Resectable and borderline Resectable pancreatic Cancer. Ann Surg. 2013;258:1040-50.PubMed

28.

Palmer DH, Stocken DD, Hewitt H, et al. A randomized phase 2 trial of neoadjuvant chemotherapy in resectable pancreatic cancer: gemcitabine alone versus gemcitabine combined with cisplatin. Ann Surg Oncol. 2007;14:2088–96.PubMed

29.

Varadhachary GR, Wolff RA, Crane CH, et al. Preoperative gemcitabine and cisplatin followed by gemcitabine-based chemoradiation for resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26:3487–95.PubMed

30.

Evans DB, Varadhachary GR, Crane CH, et al. Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26:3496–502.PubMed

31.

White RR, Hurwitz HI, Morse MA, et al. Neoadjuvant chemoradiation for localized adenocarcinoma of the pancreas. Ann Surg Oncol. 2001;8:758–65.PubMed

32.

Reni M, Balzano G, Aprile G, et al. Adjuvant PEFG (cisplatin, epirubicin, 5-fluorouracil, gemcitabine) or gemcitabine followed by chemoradiation in pancreatic cancer: a randomized phase II trial. Ann Surg Oncol. 2012;19:2256–63.PubMed

33.

Picozzi VJ, Abrams RA, Decker PA, et al. Multicenter phase II trial of adjuvant therapy for resected pancreatic cancer using cisplatin, 5-fluorouracil, and interferon-alfa-2b-based chemoradiation: ACOSOG trial Z05031. Ann Oncol. 2011;22:348–54.PubMed

34.

Takahashi H, Ohigashi H, Gotoh K, et al. Preoperative gemcitabine-based chemoradiation therapy for resectable and borderline resectable pancreatic cancer. Ann Surg. 2013;258:1040–50.PubMed

35.

Mokdad AA, Minter RM, Zhu H, et al. Neoadjuvant therapy followed by resection versus upfront resection for Resectable pancreatic Cancer: a propensity score matched analysis. J Clin Oncol. 2017;35:515–22.PubMed

36.

Suker M, Beumer BR, Sadot E, et al. FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. Lancet Oncol. 2016;17:801–10.PubMedPubMedCentral

37.

Rombouts SJ, Walma MS, Vogel JA, et al. Systematic review of resection rates and clinical outcomes after FOLFIRINOX-based treatment in patients with locally advanced pancreatic Cancer. Ann Surg Oncol. 2016;23:4352–60.PubMedPubMedCentral

38.

Pietrasz D, Marthey L, Wagner M, et al. Pathologic major response after FOLFIRINOX is prognostic for patients secondary resected for borderline or locally advanced pancreatic adenocarcinoma: an AGEO-FRENCH, prospective, multicentric cohort. Ann Surg Oncol. 2015;22(Suppl 3):S1196–205.PubMed

39.

Ferrone CR, Marchegiani G, Hong TS, et al. Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg. 2015;261:12–7.PubMed

40.

Ghosn M, Saroufim A, Kattan J, et al. Sequential FOLFOX-6 and gemcitabine for locally advanced and/or metastatic pancreatic cancer. Med Oncol. 2012;29:2831–7.PubMed

41.

Oettle H, Riess H, Stieler JM, et al. Second-line oxaliplatin, folinic acid, and fluorouracil versus folinic acid and fluorouracil alone for gemcitabine-refractory pancreatic cancer: outcomes from the CONKO-003 trial. J Clin Oncol. 2014;32:2423–9.PubMed

42.

Bonnetain F, Bonsing B, Conroy T, et al. Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (definition for the assessment of time-to-event end-points in CANcer trials). Eur J Cancer. 2014;50:2983–93.PubMed

43.

Bellera CA, Pulido M, Gourgou S, et al. Protocol of the definition for the assessment of time-to-event endpoints in CANcer trials (DATECAN) project: formal consensus method for the development of guidelines for standardised time-to-event endpoints' definitions in cancer clinical trials. Eur J Cancer. 2013;49:769–81.PubMed

44.

Fitzsimmons D, Johnson CD, George S, et al. Development of a disease specific quality of life (QoL) questionnaire module to supplement the EORTC core cancer QoL questionnaire, the QLQ-C30 in patients with pancreatic cancer. EORTC Study Group on Quality of Life. Eur J Cancer. 1999;35:939–41.PubMed

45.

Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240:205–13.PubMedPubMedCentral

46.

Bassi C, Dervenis C, Butturini G, et al. Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery. 2005;138:8–13.PubMed

47.

Kim HW, Lee JC, Paik KH, et al. Adjunctive role of preoperative liver magnetic resonance imaging for potentially resectable pancreatic cancer. Surgery. 2017;161:1579–87.PubMed

48.

Jeon SK, Lee JM, Joo I, et al. Magnetic resonance with diffusion-weighted imaging improves assessment of focal liver lesions in patients with potentially resectable pancreatic cancer on CT. Eur Radiol. 2018;28(8):3484–93.PubMed

49.

van der Gaag NA, Rauws EA, van Eijck CH, et al. Preoperative biliary drainage for cancer of the head of the pancreas. N Engl J Med. 2010;362:129–37.PubMed

50.

Tol JA, van Hooft JE, Timmer R, et al. Metal or plastic stents for preoperative biliary drainage in resectable pancreatic cancer. Gut. 2016;65:1981–7.PubMed

51.

Slim K, Blay JY, Brouquet A, et al. Digestive oncology: surgical practices. J Chir. 2009;146(Suppl 2):S11–80.

52.

Mitchem JB, Hamilton N, Gao F, et al. Long-term results of resection of adenocarcinoma of the body and tail of the pancreas using radical antegrade modular pancreatosplenectomy procedure. J Am Coll Surg. 2012;214:46–52.PubMed

53.

Verbeke CS, Menon KV. Redefining resection margin status in pancreatic cancer. HPB (Oxford). 2009;11:282–9.

54.

Bryant J, Day R. Incorporating toxicity considerations into the design of two-stage phase II clinical trials. Biometrics. 1995;51:1372–83.PubMed

55.

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; 776–782; discussion 782–774.

56.

Spitz FR, Abbruzzese JL, Lee JE, et al. Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas. J Clin Oncol. 1997;15:928–37.PubMed

57.

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.PubMed

58.

Herman JM, Swartz 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.PubMed

59.

Schorn S, Demir IE, Reyes CM, et al. The impact of neoadjuvant therapy on the histopathological features of pancreatic ductal adenocarcinoma - a systematic review and meta-analysis. Cancer Treat Rev. 2017;55:96–106.PubMed

60.

Kanda M, Fujii T, Sahin TT, et al. Invasion of the splenic artery is a crucial prognostic factor in carcinoma of the body and tail of the pancreas. Ann Surg. 2010;251:483–7.PubMed

61.

Schnelldorfer T, Ware AL, Sarr MG, et al. Long-term survival after pancreatoduodenectomy for pancreatic adenocarcinoma: is cure possible? Ann Surg. 2008;247:456–62.PubMed

62.

Rajagopalan MS, Heron DE, Wegner RE, et al. Pathologic response with neoadjuvant chemotherapy and stereotactic body radiotherapy for borderline resectable and locally-advanced pancreatic cancer. Radiat Oncol. 2013;8:254.PubMedPubMedCentral

63.

Katz MH, Shi Q, Ahmad SA, et al. Preoperative modified FOLFIRINOX treatment followed by Capecitabine-based Chemoradiation for borderline Resectable pancreatic Cancer: alliance for clinical trials in oncology trial A021101. JAMA Surg. 2016;151:e161137.PubMedPubMedCentral

64.

Burris HA 3rd, Moore MJ, Andersen J, et al. 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;15:2403–13.PubMed

65.

Maisey N, Chau I, Cunningham D, et al. Multicenter randomized phase III trial comparing protracted venous infusion (PVI) fluorouracil (5-FU) with PVI 5-FU plus mitomycin in inoperable pancreatic cancer. J Clin Oncol. 2002;20:3130–6.PubMed

66.

Colucci G, Giuliani F, Gebbia V, et al. Gemcitabine alone or with cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma: a prospective, randomized phase III study of the Gruppo Oncologia dell'Italia Meridionale. Cancer. 2002;94:902–10.PubMed

67.

Colucci G, Labianca R, Di Costanzo F, et al. Randomized phase III trial of gemcitabine plus cisplatin compared with single-agent gemcitabine as first-line treatment of patients with advanced pancreatic cancer: the GIP-1 study. J Clin Oncol. 2010;28:1645–51.PubMed

68.

Heinemann V, Wilke H, Mergenthaler HG, et al. Gemcitabine and cisplatin in the treatment of advanced or metastatic pancreatic cancer. Ann Oncol. 2000;11:1399–403.PubMed

69.

Louvet C, Labianca R, Hammel P, et al. Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol. 2005;23:3509–16.PubMed

70.

Poplin E, Feng Y, Berlin J, et al. Phase III, randomized study of gemcitabine and oxaliplatin versus gemcitabine (fixed-dose rate infusion) compared with gemcitabine (30-minute infusion) in patients with pancreatic carcinoma E6201: a trial of the eastern cooperative oncology group. J Clin Oncol. 2009;27:3778–85.PubMedPubMedCentral

71.

Wagner AD, Buechner-Steudel P, Wein A, et al. Gemcitabine, oxaliplatin and weekly high-dose 5-FU as 24-h infusion in chemonaive patients with advanced or metastatic pancreatic adenocarcinoma: a multicenter phase II trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Ann Oncol. 2007;18:82–7.PubMed

72.

Novarino A, Chiappino I, Bertelli GF, et al. Phase II study of cisplatin, gemcitabine and 5-fluorouracil in advanced pancreatic cancer. Ann Oncol. 2004;15:474–7.PubMed

73.

Hess V, Pratsch S, Potthast S, et al. Combining gemcitabine, oxaliplatin and capecitabine (GEMOXEL) for patients with advanced pancreatic carcinoma (APC): a phase I/II trial. Ann Oncol. 2010;21:2390–5.PubMed

74.

Correale P, Montagnani F, Miano S, et al. Biweekly triple combination chemotherapy with gemcitabine, oxaliplatin, levofolinic acid and 5-fluorouracil (GOLF) is a safe and active treatment for patients with inoperable pancreatic cancer. J Chemother. 2008;20:119–25.PubMed

75.

Conroy T, Paillot B, Francois E, et al. Irinotecan plus oxaliplatin and leucovorin-modulated fluorouracil in advanced pancreatic cancer--a Groupe Tumeurs digestives of the federation Nationale des Centres de Lutte Contre le Cancer study. J Clin Oncol. 2005;23:1228–36.PubMed

76.

Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. New England J medicine. 2011;364:1817–25.

77.

Gunturu KS, Yao X, Cong X, et al. FOLFIRINOX for locally advanced and metastatic pancreatic cancer: single institution retrospective review of efficacy and toxicity. Med Oncol. 2013;30(361)

78.

Marthey L, Sa-Cunha A, Blanc JF, et al. FOLFIRINOX for locally advanced pancreatic adenocarcinoma: results of an AGEO multicenter prospective observational cohort. Ann Surg Oncol. 2015;22:295-301.PubMed

79.

Goel A, Grossbard ML, Malamud S, et al. Pooled efficacy analysis from a phase I-II study of biweekly irinotecan in combination with gemcitabine, 5-fluorouracil, leucovorin and cisplatin in patients with metastatic pancreatic cancer. Anti-Cancer Drugs. 2007;18:263–71.PubMed

80.

Reni M, Sartori N, Mambrini A, et al. An Italian study on treatment trends and outcomes of patients with stage III pancreatic adenocarcinoma in the gemcitabine era: is it time to change? Anti-Cancer Drugs. 2010;21:459–64.PubMed

81.

Farrell JJ, Elsaleh H, Garcia M, et al. Human equilibrative nucleoside transporter 1 levels predict response to gemcitabine in patients with pancreatic cancer. Gastroenterology. 2009;136:187–95.PubMed

82.

Marechal R, Bachet JB, Mackey JR, et al. Levels of gemcitabine transport and metabolism proteins predict survival times of patients treated with gemcitabine for pancreatic adenocarcinoma. Gastroenterology. 2012;143:664–74. e661–666PubMed

83.

Bird NT, Elmasry M, Jones R, et al. Immunohistochemical hENT1 expression as a prognostic biomarker in patients with resected pancreatic ductal adenocarcinoma undergoing adjuvant gemcitabine-based chemotherapy. Br J Surg. 2017;104:328–36.PubMed

84.

Yamada R, Mizuno S, Uchida K, et al. Human Equilibrative nucleoside transporter 1 expression in endoscopic ultrasonography-guided fine-needle aspiration biopsy samples is a strong predictor of clinical response and survival in the patients with pancreatic ductal adenocarcinoma undergoing gemcitabine-based Chemoradiotherapy. Pancreas. 2016;45:761–71.PubMedPubMedCentral

85.

Lutz MP, Zalcberg JR, Ducreux M, et al. 3rd St. Gallen EORTC gastrointestinal Cancer conference: consensus recommendations on controversial issues in the primary treatment of pancreatic cancer. Eur J Cancer. 2017;79:41–9.PubMed

86.

Hosein PJ, Macintyre J, Kawamura C, et al. A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma. BMC Cancer. 2012;12(199)

87.

Faris JE, Blaszkowsky LS, McDermott S, et al. FOLFIRINOX in locally advanced pancreatic cancer: the Massachusetts General Hospital Cancer center experience. Oncologist. 2013;18:543–8.PubMedPubMedCentral

88.

Ducreux M, Mitry E, Ould-Kaci M, et al. Randomized phase II study evaluating oxaliplatin alone, oxaliplatin combined with infusional 5-FU, and infusional 5-FU alone in advanced pancreatic carcinoma patients. Ann Oncol. 2004;15:467–73.PubMed

89.

Ghosn M, Farhat F, Kattan J, et al. FOLFOX-6 combination as the first-line treatment of locally advanced and/or metastatic pancreatic cancer. Am J Clin Oncol. 2007;30:15–20.PubMed

90.

Gebbia V, Maiello E, Giuliani F, et al. Second-line chemotherapy in advanced pancreatic carcinoma: a multicenter survey of the Gruppo Oncologico Italia Meridionale on the activity and safety of the FOLFOX4 regimen in clinical practice. Ann Oncol. 2007;18(Suppl 6):vi124–7.PubMed

91.

Novarino A, Satolli MA, Chiappino I, et al. Oxaliplatin, 5-fluorouracil, and leucovorin as second-line treatment for advanced pancreatic cancer. Am J Clin Oncol. 2009;32:44–8.PubMed

92.

Pelzer U, Schwaner I, Stieler J, et al. Best supportive care (BSC) versus oxaliplatin, folinic acid and 5-fluorouracil (OFF) plus BSC in patients for second-line advanced pancreatic cancer: a phase III-study from the German CONKO-study group. Eur J Cancer. 2011;47:1676–81.PubMed

93.

Yoo C, Hwang JY, Kim JE, et al. A randomised phase II study of modified FOLFIRI.3 vs modified FOLFOX as second-line therapy in patients with gemcitabine-refractory advanced pancreatic cancer. Br J Cancer. 2009;101:1658–63.PubMedPubMedCentral

94.

Zaanan A, Trouilloud I, Markoutsaki T, et al. FOLFOX as second-line chemotherapy in patients with pretreated metastatic pancreatic cancer from the FIRGEM study. BMC Cancer. 2014;14(441)

Title: Resectable pancreatic adenocarcinoma neo-adjuvant FOLF(IRIN)OX-based chemotherapy - a multicenter, non-comparative, randomized, phase II trial (PANACHE01-PRODIGE48 study)
Authors: Lilian Schwarz
Dewi Vernerey
Jean-Baptiste Bachet
Jean-Jacques Tuech
Fabienne Portales
Pierre Michel
Antonio Sa Cunha
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-018-4663-4

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