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05.11.2018 | REVIEW ARTICLE

Neoadjuvant and adjuvant chemotherapy in pancreatic cancer

verfasst von: Ulla Klaiber, Carl-Stephan Leonhardt, Oliver Strobel, Christine Tjaden, Thilo Hackert, John P. Neoptolemos

Erschienen in: Langenbeck's Archives of Surgery | Ausgabe 8/2018

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Abstract

Background

Only 15–20% of patients with pancreatic ductal adenocarcinoma (PDAC) have a resectable tumor at the time of diagnosis. Effective multimodal treatment concepts including neoadjuvant chemotherapy are therefore needed. Following upfront resection, adjuvant chemotherapy has become mandatory to prevent early tumor recurrence.

Purpose

The aim of this article was to summarize existing evidence on neoadjuvant and adjuvant chemotherapy in PDAC with a focus on high-level evidence based on randomized controlled phase III clinical trials.

Results and conclusions

Neoadjuvant chemotherapy represents an emerging concept for borderline resectable and locally advanced PDAC. To date, randomized trials have failed to provide proof-of-concept outcomes, mostly because of failure to achieve recruitment targets. Nevertheless, this approach needs to be further evaluated scientifically as recent data from a large single-arm cohort study showed that neoadjuvant multimodal therapy could achieve a resection rate in the order of 60% of patients with locally advanced PDAC. For patients with a primarily resectable tumor, however, study results remain unconvincing, and therefore, neoadjuvant therapy should not be used routinely outside of a clinical trial. Adjuvant chemotherapy with gemcitabine and capecitabine in unselected patients can double 5-year overall survival to around 30% compared to mono-chemotherapy with either 5-fluorouracil with folinic acid or gemcitabine. In selected patients, adjuvant modified FOLFIRINOX can produce a 5-year survival rate of around 50%. Further potential gains are to be made in the selection of patients for particular therapies based on the transcriptomic and genetic signature of individual tumors.

Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68(1):7–30. https://doi.org/10.3322/caac.21442 CrossRefPubMed

Kleeff J, Korc M, Apte M, La Vecchia C, Johnson CD, Biankin AV, Neale RE, Tempero M, Tuveson DA, Hruban RH, Neoptolemos JP (2016) Pancreatic cancer. Nat Dis Primers 2:16022. https://doi.org/10.1038/nrdp.2016.22 CrossRef

Neoptolemos JP, Kleeff J, Michl P, Costello E, Greenhalf W, Palmer DH (2018) Therapeutic developments in pancreatic cancer: current and future perspectives. Nat Rev Gastroenterol Hepatol 15(6):333–348. https://doi.org/10.1038/s41575-018-0005-x CrossRefPubMed

Tuveson DA, Neoptolemos JP (2012) Understanding metastasis in pancreatic cancer: a call for new clinical approaches. Cell 148(1–2):21–23. https://doi.org/10.1016/j.cell.2011.12.021 CrossRefPubMed

Strobel O NJ, Jäger D, Markus W. Büchler MW (2018) Optimizing the outcomes of pancreatic cancer surgery. Nat Rev Clin Oncol. https://doi.org/10.1038/s41571-018-0112-1

Hackert T (2018) Surgery for pancreatic cancer after neoadjuvant treatment. Ann Gastroenterol Surg. https://doi.org/10.1002/ags3.12203

Callery MP, Chang KJ, Fishman EK, Talamonti MS, William Traverso L, Linehan DC (2009) Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement. Ann Surg Oncol 16(7):1727–1733. https://doi.org/10.1245/s10434-009-0408-6 CrossRefPubMed

Varadhachary GR, Tamm EP, Abbruzzese JL, Xiong HQ, Crane CH, Wang H, Lee JE, Pisters PW, Evans DB, Wolff RA (2006) Borderline resectable pancreatic cancer: definitions, management, and role of preoperative therapy. Ann Surg Oncol 13(8):1035–1046. https://doi.org/10.1245/aso.2006.08.011 CrossRefPubMed

Katz MH, Pisters PW, Evans DB, Sun CC, Lee JE, Fleming JB, Vauthey JN, Abdalla EK, Crane CH, Wolff RA, Varadhachary GR, Hwang RF (2008) Borderline resectable pancreatic cancer: the importance of this emerging stage of disease. J Am Coll Surg 206(5):833–846; discussion 846-838. https://doi.org/10.1016/j.jamcollsurg.2007.12.020 CrossRefPubMedPubMedCentral

10.

Bockhorn M, Uzunoglu FG, Adham M, Imrie C, Milicevic M, Sandberg AA, Asbun HJ, Bassi C, Buchler M, Charnley RM, Conlon K, Cruz LF, Dervenis C, Fingerhutt A, Friess H, Gouma DJ, Hartwig W, Lillemoe KD, Montorsi M, Neoptolemos JP, Shrikhande SV, Takaori K, Traverso W, Vashist YK, Vollmer C, Yeo CJ, Izbicki JR (2014) Borderline resectable pancreatic cancer: a consensus statement by the International Study Group of Pancreatic Surgery (ISGPS). Surgery 155(6):977–988. https://doi.org/10.1016/j.surg.2014.02.001 CrossRefPubMed

11.

Hackert T, Ulrich A, Buchler MW (2017) Can neoadjuvant therapy in pancreatic cancer increase the pool of patients eligible for pancreaticoduodenectomy? Adv Surg 51(1):1–10. https://doi.org/10.1016/j.yasu.2017.03.001 CrossRefPubMed

12.

Isaji S, Mizuno S, Windsor JA, Bassi C, Fernandez-Del Castillo C, Hackert T, Hayasaki A, Katz MHG, Kim SW, Kishiwada M, Kitagawa H, Michalski CW, Wolfgang CL (2018) International consensus on definition and criteria of borderline resectable pancreatic ductal adenocarcinoma 2017. Pancreatology 18(1):2–11. https://doi.org/10.1016/j.pan.2017.11.011 CrossRefPubMed

13.

Katz MH, Fleming JB, Bhosale P, Varadhachary G, Lee JE, Wolff R, Wang H, Abbruzzese J, Pisters PW, Vauthey JN, Charnsangavej C, Tamm E, Crane CH, Balachandran A (2012) Response of borderline resectable pancreatic cancer to neoadjuvant therapy is not reflected by radiographic indicators. Cancer 118(23):5749–5756. https://doi.org/10.1002/cncr.27636 CrossRefPubMed

14.

Wolfgang CL, Herman JM, Laheru DA, Klein AP, Erdek MA, Fishman EK, Hruban RH (2013) Recent progress in pancreatic cancer. CA Cancer J Clin 63(5):318–348. https://doi.org/10.3322/caac.21190 CrossRefPubMedPubMedCentral

15.

Lee ES, Lee JM (2014) Imaging diagnosis of pancreatic cancer: a state-of-the-art review. World J Gastroenterol 20(24):7864–7877. https://doi.org/10.3748/wjg.v20.i24.7864 CrossRefPubMedPubMedCentral

16.

Somers I, Bipat S (2017) Contrast-enhanced CT in determining resectability in patients with pancreatic carcinoma: a meta-analysis of the positive predictive values of CT. Eur Radiol 27(8):3408–3435. https://doi.org/10.1007/s00330-016-4708-5 CrossRefPubMedPubMedCentral

17.

Motosugi U, Ichikawa T, Morisaka H, Sou H, Muhi A, Kimura K, Sano K, Araki T (2011) Detection of pancreatic carcinoma and liver metastases with gadoxetic acid-enhanced MR imaging: comparison with contrast-enhanced multi-detector row CT. Radiology 260(2):446–453. https://doi.org/10.1148/radiol.11103548 CrossRefPubMed

18.

Tsurusaki M, Sofue K, Murakami T (2016) Current evidence for the diagnostic value of gadoxetic acid-enhanced magnetic resonance imaging for liver metastasis. Hepatol Res 46(9):853–861. https://doi.org/10.1111/hepr.12646 CrossRefPubMed

19.

Pancreatic cancer in adults: diagnosis and management NICE guideline [NG85]. Published date: 7th February 2018. Guideline Committee Clinical Lead: JP Neoptolemos. https://www.nice.org.uk/guidance/ng85

20.

Allen VB, Gurusamy KS, Takwoingi Y, Kalia A, Davidson BR (2016) Diagnostic accuracy of laparoscopy following computed tomography (CT) scanning for assessing the resectability with curative intent in pancreatic and periampullary cancer. Cochrane Database Syst Rev 7:Cd009323. https://doi.org/10.1002/14651858.CD009323.pub3 CrossRefPubMed

21.

Halloran CM, Ghaneh P, Connor S, Sutton R, Neoptolemos JP, Raraty MG (2008) Carbohydrate antigen 19.9 accurately selects patients for laparoscopic assessment to determine resectability of pancreatic malignancy. Br J Surg 95(4):453–459. https://doi.org/10.1002/bjs.6043 CrossRefPubMed

22.

Ghaneh P, Hanson R, Titman A, Lancaster G, Plumpton C, Lloyd-Williams H, Yeo ST, Edwards RT, Johnson C, Abu Hilal M, Higginson AP, Armstrong T, Smith A, Scarsbrook A, McKay C, Carter R, Sutcliffe RP, Bramhall S, Kocher HM, Cunningham D, Pereira SP, Davidson B, Chang D, Khan S, Zealley I, Sarker D, Al Sarireh B, Charnley R, Lobo D, Nicolson M, Halloran C, Raraty M, Sutton R, Vinjamuri S, Evans J, Campbell F, Deeks J, Sanghera B, Wong WL, Neoptolemos JP (2018) PET-PANC: multicentre prospective diagnostic accuracy and health economic analysis study of the impact of combined modality 18fluorine-2-fluoro-2-deoxy-d-glucose positron emission tomography with computed tomography scanning in the diagnosis and management of pancreatic cancer. Health Technol Assess (Winchester, England) 22(7):1–114. https://doi.org/10.3310/hta22070 CrossRef

23.

Gillen S, Schuster T, Meyer Zum Buschenfelde C, Friess H, Kleeff J (2010) Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med 7(4):e1000267. https://doi.org/10.1371/journal.pmed.1000267 CrossRefPubMedPubMedCentral

24.

Klaassen DJ, MacIntyre JM, Catton GE, Engstrom PF, Moertel CG (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(3):373–378. https://doi.org/10.1200/jco.1985.3.3.373 CrossRefPubMed

25.

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(10):751–755CrossRef

26.

Chauffert B, Mornex F, Bonnetain F, Rougier P, Mariette C, Bouche O, Bosset JF, Aparicio T, Mineur L, Azzedine A, Hammel P, Butel J, Stremsdoerfer N, Maingon P, Bedenne L (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):1592–1599. https://doi.org/10.1093/annonc/mdn281 CrossRefPubMed

27.

Loehrer PJ Sr, Feng Y, Cardenes H, Wagner L, Brell JM, Cella D, Flynn P, Ramanathan RK, Crane CH, Alberts SR, Benson AB III (2011) Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial. J Clin Oncol 29(31):4105–4112. https://doi.org/10.1200/jco.2011.34.8904 CrossRefPubMedPubMedCentral

28.

Hammel P, Huguet F, van Laethem JL, Goldstein D, Glimelius B, Artru P, Borbath I, Bouche O, Shannon J, Andre T, Mineur L, Chibaudel B, Bonnetain F, Louvet C (2016) Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: the LAP07 randomized clinical trial. JAMA 315(17):1844–1853. https://doi.org/10.1001/jama.2016.4324 CrossRefPubMed

29.

Golcher H, Brunner TB, Witzigmann H, Marti L, Bechstein WO, Bruns C, Jungnickel H, Schreiber S, Grabenbauer GG, Meyer T, Merkel S, Fietkau R, Hohenberger W (2015) Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer: results of the first prospective randomized phase II trial. Strahlenther Onkol 191(1):7–16. https://doi.org/10.1007/s00066-014-0737-7 CrossRefPubMed

30.

Casadei R, Di Marco M, Ricci C, Santini D, Serra C, Calculli L, D'Ambra M, Guido A, Morselli-Labate AM, Minni F (2015) Neoadjuvant chemoradiotherapy and surgery versus surgery alone in resectable pancreatic cancer: a single-center prospective, randomized, controlled trial which failed to achieve accrual targets. J Gastrointest Surg 19(10):1802–1812. https://doi.org/10.1007/s11605-015-2890-4 CrossRefPubMed

31.

Jang JY, Han Y, Lee H, Kim SW, Kwon W, Lee KH, Oh DY, Chie EK, Lee JM, Heo JS, Park JO, Lim DH, Kim SH, Park SJ, Lee WJ, Koh YH, Park JS, Yoon DS, Lee IJ, Choi SH (2018) Oncological benefits of neoadjuvant chemoradiation with gemcitabine versus upfront surgery in patients with borderline resectable pancreatic cancer: a prospective, randomized, open-label, multicenter phase 2/3 trial. Ann Surg 268(2):215–222. https://doi.org/10.1097/sla.0000000000002705 CrossRefPubMed

32.

Van Tienhoven GSM, Groothuis KB, Busch OR, Bonsing BA, de Hingh IH et al (2018) Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC-1) : a randomized, controlled, multicenter phase III trial. Journal Clinical Oncology 36, abstr:LBA4002CrossRef

33.

Strobel O, Hank T, Hinz U, Bergmann F, Schneider L, Springfeld C, Jager D, Schirmacher P, Hackert T, Buchler MW (2017) Pancreatic cancer surgery: the new R-status counts. Ann Surg 265(3):565–573. https://doi.org/10.1097/sla.0000000000001731 CrossRefPubMed

34.

Hank T, Hinz U, Tarantino I, Kaiser J, Niesen W, Bergmann F, Hackert T, Buchler MW, Strobel O (2018) Validation of at least 1 mm as cut-off for resection margins for pancreatic adenocarcinoma of the body and tail. Br J Surg 105:1171–1181. https://doi.org/10.1002/bjs.10842 CrossRefPubMed

35.

Merkow RP, Bilimoria KY, Tomlinson JS, Paruch JL, Fleming JB, Talamonti MS, Ko CY, Bentrem DJ (2014) Postoperative complications reduce adjuvant chemotherapy use in resectable pancreatic cancer. Ann Surg 260(2):372–377. https://doi.org/10.1097/sla.0000000000000378 CrossRefPubMed

36.

Bassi C, Stocken DD, Olah A, Friess H, Buckels J, Hickey H, Dervenis C, Dunn JA, Deakin M, Carter R, Ghaneh P, Neoptolemos JP, Buchler MW (2005) Influence of surgical resection and post-operative complications on survival following adjuvant treatment for pancreatic cancer in the ESPAC-1 randomized controlled trial. Dig Surg 22(5):353–363. https://doi.org/10.1159/000089771 CrossRefPubMed

37.

Motoi F, Ishida K, Fujishima F, Ottomo S, Oikawa M, Okada T, Shimamura H, Takemura S, Ono F, Akada M, Nakagawa K, Katayose Y, Egawa S, Unno M (2013) 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 20(12):3794–3801. https://doi.org/10.1245/s10434-013-3129-9 CrossRefPubMed

38.

Hoffman JP, Lipsitz S, Pisansky T, Weese JL, Solin L, Benson AB 3rd (1998) Phase II trial of preoperative radiation therapy and chemotherapy for patients with localized, resectable adenocarcinoma of the pancreas: an Eastern Cooperative Oncology gGroup Study. J Clin Oncol 16(1):317–323. https://doi.org/10.1200/jco.1998.16.1.317 CrossRefPubMed

39.

Schwarz L, Vernerey D, Bachet J-B, Tuech J-J, Portales F, Michel P, Cunha AS (2018) Resectable pancreatic adenocarcinoma neo-adjuvant FOLF(IRIN)OX-based chemotherapy - a multicenter, non-comparative, randomized, phase II trial (PANACHE01-PRODIGE48 study). BMC Cancer 18:762. https://doi.org/10.1186/s12885-018-4663-4 CrossRefPubMedPubMedCentral

40.

Heinrich S, Pestalozzi B, Lesurtel M, Berrevoet F, Laurent S, Delpero JR, Raoul JL, Bachellier P, Dufour P, Moehler M, Weber A, Lang H, Rogiers X, Clavien PA (2011) Adjuvant gemcitabine versus NEOadjuvant gemcitabine/oxaliplatin plus adjuvant gemcitabine in resectable pancreatic cancer: a randomized multicenter phase III study (NEOPAC study). BMC Cancer 11:346. https://doi.org/10.1186/1471-2407-11-346 CrossRefPubMedPubMedCentral

41.

Murphy JE, Wo JY, Ryan DP, Jiang W, Yeap BY, Drapek LC, Blaszkowsky LS, Kwak EL, Allen JN, Clark JW, Faris JE, Zhu AX, Goyal L, Lillemoe KD, DeLaney TF, Fernandez-Del Castillo C, Ferrone CR, Hong TS (2018) Total neoadjuvant therapy with FOLFIRINOX followed by individualized chemoradiotherapy for borderline resectable pancreatic adenocarcinoma: a phase 2 clinical trial. JAMA Oncol 4(7):963–969. https://doi.org/10.1001/jamaoncol.2018.0329 CrossRefPubMedPubMedCentral

42.

Hartwig W, Gluth A, Hinz U, Koliogiannis D, Strobel O, Hackert T, Werner J, Buchler MW (2016) Outcomes after extended pancreatectomy in patients with borderline resectable and locally advanced pancreatic cancer. Br J Surg 103(12):1683–1694. https://doi.org/10.1002/bjs.10221 CrossRefPubMed

43.

Hackert T, Ulrich A, Buchler MW (2016) Borderline resectable pancreatic cancer. Cancer Lett 375(2):231–237. https://doi.org/10.1016/j.canlet.2016.02.039 CrossRefPubMed

44.

ISRCTN: https://doi.org/10.1186/ISRCTN89500674

45.

Hackert T, Sachsenmaier M, Hinz U, Schneider L, Michalski CW, Springfeld C, Strobel O, Jager D, Ulrich A, Buchler MW (2016) Locally advanced pancreatic cancer: neoadjuvant therapy with Folfirinox results in resectability in 60% of the patients. Ann Surg 264(3):457–463. https://doi.org/10.1097/sla.0000000000001850 CrossRefPubMed

46.

Suker M, Beumer BR, Sadot E, Marthey L, Faris JE, Mellon EA, El-Rayes BF, Wang-Gillam A, Lacy J, Hosein PJ, Moorcraft SY, Conroy T, Hohla F, Allen P, Taieb J, Hong TS, Shridhar R, Chau I, van Eijck CH, Koerkamp BG (2016) FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. Lancet Oncol 17(6):801–810. https://doi.org/10.1016/s1470-2045(16)00172-8 CrossRefPubMedPubMedCentral

47.

Ferrone CR, Marchegiani G, Hong TS, Ryan DP, Deshpande V, McDonnell EI, Sabbatino F, Santos DD, Allen JN, Blaszkowsky LS, Clark JW, Faris JE, Goyal L, Kwak EL, Murphy JE, Ting DT, Wo JY, Zhu AX, Warshaw AL, Lillemoe KD, Fernandez-del Castillo C (2015) Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg 261(1):12–17. https://doi.org/10.1097/sla.0000000000000867 CrossRefPubMed

48.

Hackert T, Strobel O, Michalski CW, Mihaljevic AL, Mehrabi A, Muller-Stich B, Berchtold C, Ulrich A, Buchler MW (2017) The TRIANGLE operation - radical surgery after neoadjuvant treatment for advanced pancreatic cancer: a single arm observational study. HPB 19(11):1001–1007. https://doi.org/10.1016/j.hpb.2017.07.007 CrossRefPubMed

49.

Hartwig W, Gluth A, Hinz U, Bergmann F, Spronk PE, Hackert T, Werner J, Buchler MW (2015) Total pancreatectomy for primary pancreatic neoplasms: renaissance of an unpopular operation. Ann Surg 261(3):537–546. https://doi.org/10.1097/sla.0000000000000791 CrossRefPubMed

50.

Weitz J, Rahbari N, Koch M, Buchler MW (2010) The “artery first” approach for resection of pancreatic head cancer. J Am Coll Surg 210(2):e1–e4. https://doi.org/10.1016/j.jamcollsurg.2009.10.019 CrossRefPubMed

51.

Klompmaker S, van Hilst J, Gerritsen SL, Adham M, Teresa Albiol Quer M, Bassi C, Berrevoet F, Boggi U, Busch OR, Cesaretti M, Dalla Valle R, Darnis B, De Pastena M, Del Chiaro M, Grutzmann R, Diener MK, Dumitrascu T, Friess H, Ivanecz A, Karayiannakis A, Fusai GK, Labori KJ, Lombardo C, Lopez-Ben S, Mabrut JY, Niesen W, Pardo F, Perinel J, Popescu I, Roeyen G, Sauvanet A, Prasad R, Sturesson C, Lesurtel M, Kleeff J, Salvia R, Besselink MG (2018) Outcomes after distal pancreatectomy with celiac axis resection for pancreatic cancer: a pan-European retrospective cohort study. Ann Surg Oncol 25(5):1440–1447. https://doi.org/10.1245/s10434-018-6391-z CrossRefPubMedPubMedCentral

52.

Kalser MH, Ellenberg SS (1985) Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg 120(8):899–903CrossRefPubMed

53.

Gastrointestinal Tumor Study Group (1987) Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Cancer 59(12):2006–2010CrossRef

54.

Bakkevold KE, Arnesjo B, Dahl O, Kambestad B (1993) Adjuvant combination chemotherapy (AMF) following radical resection of carcinoma of the pancreas and papilla of Vater--results of a controlled, prospective, randomised multicentre study. Eur J Cancer 29a(5):698–703CrossRefPubMed

55.

Takada T, Amano H, Yasuda H, Nimura Y, Matsushiro T, Kato H, Nagakawa T, Nakayama T (2002) Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma. Cancer 95(8):1685–1695. https://doi.org/10.1002/cncr.10831 CrossRefPubMed

56.

Klinkenbijl JH, Jeekel J, Sahmoud T, van Pel R, Couvreur ML, Veenhof CH, Arnaud JP, Gonzalez DG, de Wit LT, Hennipman A, Wils J (1999) 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 230(6):776–782 discussion 782-774CrossRefPubMedPubMedCentral

57.

Smeenk HG, van Eijck CH, Hop WC, Erdmann J, Tran KC, Debois M, van Cutsem E, van Dekken H, Klinkenbijl JH, Jeekel J (2007) Long-term survival and metastatic pattern of pancreatic and periampullary cancer after adjuvant chemoradiation or observation: long-term results of EORTC trial 40891. Ann Surg 246(5):734–740. https://doi.org/10.1097/SLA.0b013e318156eef3 CrossRefPubMed

58.

Neoptolemos JP, Dunn JA, Stocken DD, Almond J, Link K, Beger H, Bassi C, Falconi M, Pederzoli P, Dervenis C, Fernandez-Cruz L, Lacaine F, Pap A, Spooner D, Kerr DJ, Friess H, Buchler MW (2001) Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet (London, England) 358(9293):1576–1585CrossRef

59.

Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, Beger H, Fernandez-Cruz L, Dervenis C, Lacaine F, Falconi M, Pederzoli P, Pap A, Spooner D, Kerr DJ, Buchler MW (2004) A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 350(12):1200–1210. https://doi.org/10.1056/NEJMoa032295 CrossRefPubMed

60.

Carter R, Stocken DD, Ghaneh P, Bramhall SR, Olah A, Kelemen D, Bassi C, Friess H, Dervenis C, Spry N, Buchler MW, Neoptolemos JP (2009) Longitudinal quality of life data can provide insights on the impact of adjuvant treatment for pancreatic cancer-subset analysis of the ESPAC-1 data. Int J Cancer 124(12):2960–2965. https://doi.org/10.1002/ijc.24270 CrossRefPubMed

61.

Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, Schramm H, Fahlke J, Zuelke C, Burkart C, Gutberlet K, Kettner E, Schmalenberg H, Weigang-Koehler K, Bechstein WO, Niedergethmann M, Schmidt-Wolf I, Roll L, Doerken B, Riess H (2007) Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 297(3):267–277. https://doi.org/10.1001/jama.297.3.267 CrossRefPubMed

62.

Oettle H, Neuhaus P, Hochhaus A, Hartmann JT, Gellert K, Ridwelski K, Niedergethmann M, Zulke C, Fahlke J, Arning MB, Sinn M, Hinke A, Riess H (2013) Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA 310(14):1473–1481. https://doi.org/10.1001/jama.2013.279201 CrossRefPubMed

63.

Ueno H, Kosuge T, Matsuyama Y, Yamamoto J, Nakao A, Egawa S, Doi R, Monden M, Hatori T, Tanaka M, Shimada M, Kanemitsu K (2009) 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 101(6):908–915. https://doi.org/10.1038/sj.bjc.6605256 CrossRefPubMedPubMedCentral

64.

Regine WF, Winter KA, Abrams RA, Safran H, Hoffman JP, Konski A, Benson AB, Macdonald JS, Kudrimoti MR, Fromm ML, Haddock MG, Schaefer P, Willett CG, Rich TA (2008) Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA 299(9):1019–1026. https://doi.org/10.1001/jama.299.9.1019 CrossRefPubMed

65.

Regine WF, Winter KA, Abrams R, Safran H, Hoffman JP, Konski A, Benson AB, Macdonald JS, Rich TA, Willett CG (2011) 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(5):1319–1326. https://doi.org/10.1245/s10434-011-1630-6 CrossRefPubMedPubMedCentral

66.

Neoptolemos JP, Stocken DD, Bassi C, Ghaneh P, Cunningham D, Goldstein D, Padbury R, Moore MJ, Gallinger S, Mariette C, Wente MN, Izbicki JR, Friess H, Lerch MM, Dervenis C, Olah A, Butturini G, Doi R, Lind PA, Smith D, Valle JW, Palmer DH, Buckels JA, Thompson J, McKay CJ, Rawcliffe CL, Buchler MW (2010) Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA 304(10):1073–1081. https://doi.org/10.1001/jama.2010.1275 CrossRefPubMed

67.

Schmidt J, Abel U, Debus J, Harig S, Hoffmann K, Herrmann T, Bartsch D, Klein J, Mansmann U, Jager D, Capussotti L, Kunz R, Buchler MW (2012) Open-label, multicenter, randomized phase III trial of adjuvant chemoradiation plus interferon Alfa-2b versus fluorouracil and folinic acid for patients with resected pancreatic adenocarcinoma. J Clin Oncol 30(33):4077–4083. https://doi.org/10.1200/jco.2011.38.2960 CrossRefPubMed

68.

Uesaka K, Boku N, Fukutomi A, Okamura Y, Konishi M, Matsumoto I, Kaneoka Y, Shimizu Y, Nakamori S, Sakamoto H, Morinaga S, Kainuma O, Imai K, Sata N, Hishinuma S, Ojima H, Yamaguchi R, Hirano S, Sudo T, Ohashi Y (2016) Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet (London, England) 388(10041):248–257. https://doi.org/10.1016/s0140-6736(16)30583-9 CrossRef

69.

Sinn M, Bahra M, Liersch T, Gellert K, Messmann H, Bechstein W, Waldschmidt D, Jacobasch L, Wilhelm M, Rau BM, Grutzmann R, Weinmann A, Maschmeyer G, Pelzer U, Stieler JM, Striefler JK, Ghadimi M, Bischoff S, Dorken B, Oettle H, Riess H (2017) CONKO-005: adjuvant chemotherapy with gemcitabine plus erlotinib versus gemcitabine alone in patients after R0 resection of pancreatic Cancer: a multicenter randomized phase III trial. J Clin Oncol 35(29):3330–3337. https://doi.org/10.1200/jco.2017.72.6463 CrossRefPubMed

70.

Sinn M, Liersch T, Gellert K, Riess H, Stübs P, Waldschmidt DT, Pelzer U, Stieler J, Striefler JK, Bahra M, Dörken B, Oettle H (2014) LBA18CONKO-006: a randomized double-blinded phase IIB-study of adjuvant therapy with gemcitabine + SORAFENIB/placebo for patients with R1-resection of pancreatic cancer. Ann Oncol 25(suppl_4):mdu438.418–mdu438.418. https://doi.org/10.1093/annonc/mdu438.18 CrossRef

71.

Neoptolemos JP, Palmer DH, Ghaneh P, Psarelli EE, Valle JW, Halloran CM, Faluyi O, O'Reilly DA, Cunningham D, Wadsley J, Darby S, Meyer T, Gillmore R, Anthoney A, Lind P, Glimelius B, Falk S, Izbicki JR, Middleton GW, Cummins S, Ross PJ, Wasan H, McDonald A, Crosby T, Ma YT, Patel K, Sherriff D, Soomal R, Borg D, Sothi S, Hammel P, Hackert T, Jackson R, Buchler MW (2017) 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 (London, England) 389(10073):1011–1024. https://doi.org/10.1016/s0140-6736(16)32409-6 CrossRef

72.

Conroy T, Hammel P, Hebbar M, Ben Abdelghani M, AC-c W, Raoul J-L, Chone L, Francois E, Artru P, Biagi JJ, Lecomte T, Assenat E, Faroux R, Ychou M, Volet J, Sauvanet A, Jouffroy-Zeller C, Rat P, Castan F, Bachet J-B (2018) Unicancer GI PRODIGE 24/CCTG PA.6 trial: a multicenter international randomized phase III trial of adjuvant mFOLFIRINOX versus gemcitabine (gem) in patients with resected pancreatic ductal adenocarcinomas. J Clin Oncol 36(18_suppl):LBA4001–LBA4001. https://doi.org/10.1200/JCO.2018.36.18_suppl.LBA4001 CrossRef

73.

Twombly R (2008) Adjuvant chemoradiation for pancreatic cancer: few good data, much debate. J Natl Cancer Inst 100(23):1670–1671. https://doi.org/10.1093/jnci/djn428 CrossRefPubMed

74.

Valle JW, Palmer D, Jackson R, Cox T, Neoptolemos JP, Ghaneh P, Rawcliffe CL, Bassi C, Stocken DD, Cunningham D, O'Reilly D, Goldstein D, Robinson BA, Karapetis C, Scarfe A, Lacaine F, Sand J, Izbicki JR, Mayerle J, Dervenis C, Olah A, Butturini G, Lind PA, Middleton MR, Anthoney A, Sumpter K, Carter R, Buchler MW (2014) 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 32(6):504–512. https://doi.org/10.1200/jco.2013.50.7657 CrossRefPubMed

75.

Neoptolemos JP, Stocken DD, Tudur Smith C, Bassi C, Ghaneh P, Owen E, Moore M, Padbury R, Doi R, Smith D, Buchler MW (2009) Adjuvant 5-fluorouracil and folinic acid vs observation for pancreatic cancer: composite data from the ESPAC-1 and -3(v1) Trials. Br J Cancer 100(2):246–250. https://doi.org/10.1038/sj.bjc.6604838 CrossRefPubMedPubMedCentral

76.

Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Parulekar W (2007) 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 25(15):1960–1966. https://doi.org/10.1200/jco.2006.07.9525 CrossRefPubMed

77.

Cunningham D, Chau I, Stocken DD, Valle JW, Smith D, Steward W, Harper PG, Dunn J, Tudur-Smith C, West J, Falk S, Crellin A, Adab F, Thompson J, Leonard P, Ostrowski J, Eatock M, Scheithauer W, Herrmann R, Neoptolemos JP (2009) Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J ClinOncol 27(33):5513–5518. https://doi.org/10.1200/jco.2009.24.2446 CrossRef

78.

Sultana A, Ghaneh P, Cunningham D, Starling N, Neoptolemos JP, Smith CT (2008) Gemcitabine based combination chemotherapy in advanced pancreatic cancer-indirect comparison. BMC Cancer 8:192. https://doi.org/10.1186/1471-2407-8-192 CrossRefPubMedPubMedCentral

79.

Khorana AA, Mangu PB, Katz MHG (2017) Potentially curable pancreatic cancer: American Society of Clinical Oncology Clinical Practice Guideline Update Summary. J Oncol Pract 13(6):388–391. https://doi.org/10.1200/jop.2017.023044 CrossRefPubMed

80.

Mahaseth H, Brutcher E, Kauh J, Hawk N, Kim S, Chen Z, Kooby DA, Maithel SK, Landry J, El-Rayes BF (2013) Modified FOLFIRINOX regimen with improved safety and maintained efficacy in pancreatic adenocarcinoma. Pancreas 42(8):1311–1315. https://doi.org/10.1097/MPA.0b013e31829e2006 CrossRefPubMed

81.

Aguirre AJ, Nowak JA, Camarda ND, Moffitt RA, Ghazani AA, Hazar-Rethinam M, Raghavan S, Kim J, Brais LK, Ragon D, Welch MW, Reilly E, McCabe D, Marini L, Anderka K, Helvie K, Oliver N, Babic A, Da Silva A, Nadres B, Van Seventer EE, Shahzade HA, St Pierre JP, Burke KP, Clancy TE, Cleary JM, Doyle LA, Jajoo K, McCleary NJ, Meyerhardt JA, Murphy JE, Ng K, Patel AK, Perez K, Rosenthal MH, Rubinson DA, Ryou M, Shapiro GI, Sicinska E, Silverman SG, Nagy RJ, Lanman RB, Knoerzer D, Welsch DJ, Yurgelun MB, Fuchs CS, Garraway LA, Getz G, Hornick JL, Johnson BE, Kulke MH, Mayer RJ, Miller JW, Shyn PB, Tuveson DA, Wagle N, Yeh JJ, Hahn WC, Corcoran RB, Carter SL, Wolpin BM (2018) Real-time genomic characterization of advanced pancreatic cancer to enable precision medicine. Cancer Discov 8:1096–1111. https://doi.org/10.1158/2159-8290.Cd-18-0275 CrossRefPubMedPubMedCentral

82.

Tiriac H, Belleau P, Engle DD, Plenker D, Deschenes A, Somerville T, Froeling FEM, Burkhart RA, Denroche RE, Jang GH, Miyabayashi K, Young CM, Patel H, Ma M, LaComb JF, Palmaira RLD, Javed AA, Huynh JA, Johnson M, Arora K, Robine N, Shah M, Sanghvi R, Goetz AB, Lowder CY, Martello L, Driehuis E, Lecomte N, Askan G, Iacobuzio-Donahue CA, Clevers H, Wood LD, Hruban RH, Thompson ED, Aguirre AJ, Wolpin BM, Sasson A, Kim J, Wu M, Bucobo JC, Allen PJ, Sejpal DV, Nealon W, Sullivan JD, Winter JM, Gimotty PA, Grem JL, DiMaio DJ, Buscaglia JM, Grandgenett PM, Brody JR, Hollingsworth MA, O'Kane GM, Notta F, Kim EJ, Crawford JM, Devoe CE, Ocean A, Wolfgang CL, Yu KH, Li E, Vakoc CR, Hubert B, Fischer SE, Wilson JM, Moffitt RA, Knox JJ, Krasnitz A, Gallinger S, Tuveson DA (2018) Organoid profiling identifies common responders to chemotherapy in pancreatic cancer. Cancer Discov 8:1112–1129. https://doi.org/10.1158/2159-8290.Cd-18-0349 CrossRefPubMedPubMedCentral

Titel: Neoadjuvant and adjuvant chemotherapy in pancreatic cancer
verfasst von: Ulla Klaiber
Carl-Stephan Leonhardt
Oliver Strobel
Christine Tjaden
Thilo Hackert
John P. Neoptolemos
Publikationsdatum: 05.11.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: Langenbeck's Archives of Surgery / Ausgabe 8/2018
Print ISSN: 1435-2443
Elektronische ISSN: 1435-2451
DOI: https://doi.org/10.1007/s00423-018-1724-8

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