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Neoadjuvante und adjuvante Therapie beim Pankreaskarzinom

Neoadjuvant and adjuvant treatment of pancreatic cancer

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Zusammenfassung

Hintergrund

Die Resektion ist die einzige kurative Therapieoption beim Pankreaskarzinom. Adjuvante Chemotherapie kann das krankheitsfreie Überleben und Gesamtüberleben nach Resektion verbessern. Zurzeit werden darüber hinaus neoadjuvante Konzepte in zahlreichen Studien untersucht.

Ziel der Arbeit

Zusammenfassung der aktuellen Datenlage bezüglich adjuvanter und neoadjuvanter Therapie des Pankreaskarzinoms.

Material und Methoden

Analyse der wissenschaftlichen Literatur und Leitlinien.

Ergebnisse und Diskussion

Nach Resektion eines Pankreaskarzinoms sollte eine möglichst intensive Chemotherapie mit mFOLFIRINOX, Gemcitabin plus Capecitabin oder Gemcitabin/5-Fluorouracil(5-FU)-Monotherapie durchgeführt werden. Neoadjuvante Konzepte sind vielversprechend, sollten aber in prospektiven Studien weiter evaluiert werden.

Abstract

Background

Resection is the only curative treatment option for pancreatic cancer patients. Adjuvant chemotherapy can improve disease-free survival and overall survival after resection. Furthermore, neoadjuvant treatment protocols are currently being investigated in a large number of studies.

Objective

Summary of the current evidence for adjuvant and neoadjuvant treatment.

Material and methods

Review of the current scientific literature and guidelines.

Results and conclusion

After resection for pancreatic cancer patients should receive intensive chemotherapy with mFOLFIRINOX, gemcitabine plus capecitabine or gemcitabine/5-fluorouracil (5-FU) monotherapy. Neoadjuvant treatment concepts are promising but have to be further evaluated in prospective studies.

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Literatur

  1. Badiyan SN, Molitoris JK, Chuong MD et al (2017) The role of radiation therapy for pancreatic cancer in the adjuvant and neoadjuvant settings. Surg Oncol Clin N Am 26:431–453

    PubMed  Google Scholar 

  2. Balachandran VP, Luksza M, Zhao JN et al (2017) Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer. Nature 551:512–516

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Burris HA 3rd, Moore MJ, Andersen 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 Oncol 15:2403–2413

    CAS  PubMed  Google Scholar 

  4. Chuong MD, Boggs DH, Patel KN et al (2014) Adjuvant chemoradiation for pancreatic cancer: what does the evidence tell us? J Gastrointest Oncol 5:166–177

    PubMed  PubMed Central  Google Scholar 

  5. Collisson EA, Bailey P, Chang DK et al (2019) Molecular subtypes of pancreatic cancer. Nat Rev Gastroenterol Hepatol 16:207–220

    PubMed  Google Scholar 

  6. Conroy T, Desseigne F, Ychou M et al (2011) FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364:1817–1825

    CAS  PubMed  Google Scholar 

  7. Conroy T, Hammel P, Hebbar M et al (2018) FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med 379:2395–2406

    CAS  PubMed  Google Scholar 

  8. Cunningham D, Chau I, Stocken DD et al (2009) Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol 27:5513–5518

    CAS  PubMed  Google Scholar 

  9. Dhir M, Zenati MS, Hamad A et al (2018) FOLFIRINOX versus gemcitabine/nab-paclitaxel for neoadjuvant treatment of resectable and borderline resectable pancreatic head adenocarcinoma. Ann Surg Oncol 25:1896–1903

    PubMed  Google Scholar 

  10. Drilon A, Laetsch TW, Kummar S et al (2018) Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. N Engl J Med 378:731–739

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Ducreux M, Cuhna AS, Caramella C et al (2015) Cancer of the pancreas: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 26(5):v56–68

    PubMed  Google Scholar 

  12. Ettrich TJ, Berger AW, Perkhofer L et al (2018) Neoadjuvant plus adjuvant or only adjuvant nab-paclitaxel plus gemcitabine for resectable pancreatic cancer—the NEONAX trial (AIO-PAK-0313), a prospective, randomized, controlled, phase II study of the AIO pancreatic cancer group. BMC Cancer 18:1298

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Furuse J, Shibahara J, Sugiyama M (2018) Development of chemotherapy and significance of conversion surgery after chemotherapy in unresectable pancreatic cancer. J Hepatobiliary Pancreat Sci 25:261–268

    PubMed  Google Scholar 

  14. Gemenetzis G, Groot VP, Blair AB et al (2019) Survival in locally advanced pancreatic cancer after neoadjuvant therapy and surgical resection. Ann Surg 270:340–347

    PubMed  Google Scholar 

  15. Ghaneh P, Kleeff J, Halloran CM et al (2019) The impact of positive resection margins on survival and recurrence following resection and adjuvant chemotherapy for pancreatic ductal adenocarcinoma. Ann Surg 269:520–529

    PubMed  Google Scholar 

  16. Golan T, Hammel P, Reni M et al (2019) Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med 381:317–327

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Hackert T, Sachsenmaier M, Hinz U et al (2016) Locally advanced pancreatic cancer: neoadjuvant therapy with folfirinox results in resectability in 60 % of the patients. Ann Surg 264:457–463

    PubMed  Google Scholar 

  18. Hall WA, Goodman KA (2019) Radiation therapy for pancreatic adenocarcinoma, a treatment option that must be considered in the management of a devastating malignancy. Radiat Oncol 14:114

    PubMed  PubMed Central  Google Scholar 

  19. Hammel P, Huguet F, van Laethem JL et al (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 315:1844–1853

    CAS  PubMed  Google Scholar 

  20. Heining C, Horak P, Uhrig S et al (2018) NRG1 fusions in KRAS wild-type pancreatic cancer. Cancer Discov 8:1087–1095

    CAS  PubMed  Google Scholar 

  21. Jang JY, Han Y, Lee H et al (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 268:215–222

    PubMed  Google Scholar 

  22. Janssen QP, Buettner S, Suker M et al (2019) Neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer: a systematic review and patient-level meta-analysis. J Natl Cancer Inst 111:782–794

    PubMed  PubMed Central  Google Scholar 

  23. Jones RP, Psarelli EE, Jackson R et al (2019) Patterns of recurrence after resection of pancreatic ductal adenocarcinoma: a secondary analysis of the ESPAC‑4 randomized adjuvant chemotherapy trial. JAMA Surg. https://doi.org/10.1001/jamasurg.2019.3337

    Article  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  25. Klinkenbijl JH, Jeekel J, Sahmoud T et al (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 230:776–782

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Kunzmann V, Algül H, Goekkurt E et al (2019) Conversion rate in locally advanced pancreatic cancer (LAPC) after nab-paclitaxel/gemcitabine- or FOLFIRINOX-based induction chemotherapy (NEOLAP): final results of a multicenter randomised phase II AIO trial. Ann Oncol 30:v253–v324

    Google Scholar 

  27. Mokdad AA, Minter RM, Zhu H et al (2017) Neoadjuvant therapy followed by resection versus upfront resection for resectable pancreatic cancer: a propensity score matched analysis. J Clin Oncol 35:515–522

    PubMed  Google Scholar 

  28. Neoptolemos JP, Dunn JA, Stocken DD et al (2001) Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet 358:1576–1585

    CAS  PubMed  Google Scholar 

  29. Neoptolemos JP, Palmer DH, Ghaneh P et al (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 389:1011–1024

    CAS  PubMed  Google Scholar 

  30. Neoptolemos JP, Stocken DD, Bassi C et al (2010) Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA 304:1073–1081

    CAS  PubMed  Google Scholar 

  31. 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 350:1200–1210

    CAS  PubMed  Google Scholar 

  32. Oettle H, Neuhaus P, Hochhaus A et al (2013) Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA 310:1473–1481

    CAS  PubMed  Google Scholar 

  33. 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 297:267–277

    CAS  PubMed  Google Scholar 

  34. Rahib L, Smith BD, Aizenberg R et al (2014) Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res 74:2913–2921

    CAS  PubMed  Google Scholar 

  35. Robert-Koch-Institut (2019) Krebs in Deutschland für 2015/2016. Robert-Koch-Institut, Berlin

    Google Scholar 

  36. Rombouts SJ, Walma MS, Vogel JA et al (2016) Systematic review of resection rates and clinical outcomes after FOLFIRINOX-based treatment in patients with locally advanced pancreatic cancer. Ann Surg Oncol 23:4352–4360

    PubMed  PubMed Central  Google Scholar 

  37. Roth MT, Berlin JD (2018) Current concepts in the treatment of resectable pancreatic cancer. Curr Oncol Rep 20:39

    PubMed  Google Scholar 

  38. Scheufele F, Hartmann D, Friess H (2019) Treatment of pancreatic cancer-neoadjuvant treatment in borderline resectable/locally advanced pancreatic cancer. Transl Gastroenterol Hepatol 4:32

    PubMed  PubMed Central  Google Scholar 

  39. Seufferlein T, Ettrich TJ (2019) Treatment of pancreatic cancer-neoadjuvant treatment in resectable pancreatic cancer (PDAC). Transl Gastroenterol Hepatol 4:21

    PubMed  PubMed Central  Google Scholar 

  40. Seufferlein T, Hammel P, Delpero JR et al (2019) Optimizing the management of locally advanced pancreatic cancer with a focus on induction chemotherapy: expert opinion based on a review of current evidence. Cancer Treat Rev 77:1–10

    PubMed  Google Scholar 

  41. Sohal DPS (2018) Point: weighing the risks and benefits of neoadjuvant therapy in resectable pancreatic cancer. Oncology (Williston Park) 32:39–44

    Google Scholar 

  42. Springfeld C, Jäger D, Büchler MW et al (2019) Chemotherapy for pancreatic cancer. Presse Med 48:e159–e174

    PubMed  Google Scholar 

  43. Strobel O, Neoptolemos J, Jäger D et al (2019) Optimizing the outcomes of pancreatic cancer surgery. Nat Rev Clin Oncol 16:11–26

    CAS  PubMed  Google Scholar 

  44. Tempero MA, Reni M, Riess H et al (2019) APACT: phase III, multicenter, international, open-label, randomized trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P/G) vs gemcitabine (G) for surgically resected pancreatic adenocarcinoma. J Clin Oncol 37:4000

    Google Scholar 

  45. Uesaka K, Boku N, Fukutomi A et al (2016) Adjuvant chemotherapy of S‑1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet 388:248–257

    CAS  PubMed  Google Scholar 

  46. Valle JW, Palmer D, Jackson R et al (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 32:504–512

    PubMed  Google Scholar 

  47. Versteijne E, Vogel JA, Besselink MG et al (2018) Meta-analysis comparing upfront surgery with neoadjuvant treatment in patients with resectable or borderline resectable pancreatic cancer. Br J Surg 105(8):946–958. https://doi.org/10.1002/bjs.10870

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Von Hoff DD, Ervin T, Arena FP et al (2013) Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369:1691–1703

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Wittel UA, Lubgan D, Ghadimi M et al (2019) Consensus in determining the resectability of locally progressed pancreatic ductal adenocarcinoma—results of the Conko-007 multicenter trial. BMC Cancer 19:979

    CAS  PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. Abteilung Medizinische Onkologie, Nationales Zentrum für Tumorerkrankungen, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 460, 69120, Heidelberg, Deutschland

    C. Springfeld & D. Jäger

  2. Klinik für Allgemein‑, Viszeral- und Transplantationschirurgie, Universitätsklinikum Heidelberg, Heidelberg, Deutschland

    T. Hackert, M. W. Büchler & J. P. Neoptolemos

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  1. C. Springfeld
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  2. T. Hackert
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  3. D. Jäger
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  4. M. W. Büchler
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  5. J. P. Neoptolemos
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Corresponding author

Correspondence to C. Springfeld.

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Interessenkonflikt

C. Springfeld, T. Hackert, D. Jäger, M.W. Büchler und J. P. Neoptolemos geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Springfeld, C., Hackert, T., Jäger, D. et al. Neoadjuvante und adjuvante Therapie beim Pankreaskarzinom. Chirurg 91, 636–641 (2020). https://doi.org/10.1007/s00104-020-01169-9

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  • DOI: https://doi.org/10.1007/s00104-020-01169-9

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