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Current Oncology Reports

, 18:60 | Cite as

Update on the Management of Pancreatic Cancer in Older Adults

  • Shin Yin Lee
  • Moussa Sissoko
  • Kevan L. Hartshorn
Geriatric Oncology (AR MacKenzie, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Geriatric Oncology

Abstract

Pancreatic cancer is more common in older adults, who are underrepresented in clinical trials and frequently under treated. Chronological age alone should not deter clinicians from offering treatment to geriatric patients, as they are a heterogeneous population. Geriatric assessment, frailty assessment tools, and toxicity risk scores help clinicians select appropriate patients for therapy. For resectable disease, surgery can be safe but should be done at a high-volume center. Adjuvant therapy is important; though there remains controversy on the role of radiation, chemotherapy is well studied and efficacious. In locally advanced unresectable disease, chemoradiation or chemotherapy alone is an option. Neoadjuvant therapy improves the chances of resectability in borderline resectable disease. Chemotherapy extends survival in metastatic disease, but treatment goals and risk-benefit ratios have to be clarified. Adequate symptom management and supportive care are important. There are now many new treatment strategies and novel therapies for this disease.

Keywords

Pancreatic adenocarcinoma Older adults Geriatric oncology Comprehensive geriatric assessment Frailty scores Toxicity scores Update Surgery Chemotherapy Radiation Chemoradiation Novel therapies Symptom management 

Notes

Compliance with Ethical Standards

Conflict of Interest

Shin Yin Lee, Moussa Sissoko, and Kevan L. Hartshorn declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, et al. Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin. 2014;64:252–71.CrossRefPubMedGoogle Scholar
  2. 2.
    Howlader N, Noone A, Krapcho M, Garshell J, Miller D, Altekruse S, et al. SEER Cancer Statistics Review, 1975–2012, National Cancer Institute. Bethesda, MD, based on November 2014 SEER data submission, posted to the SEER website, April 2015. [Internet]. [cited 2016 Feb 7]. Available from: http://seer.cancer.gov/csr/1975_2012/.
  3. 3.
    Yancik R. Population aging and cancer: a cross-national concern. Cancer J Sudbury Mass. 2005;11:437–41.CrossRefGoogle Scholar
  4. 4.
    Hanson LC, Muss HB. Cancer in the oldest old: making better treatment decisions. J Clin Oncol. 2010;28:1975–6.CrossRefPubMedGoogle Scholar
  5. 5.
    Ryan DP, Hong TS, Bardeesy N. Pancreatic adenocarcinoma. N Engl J Med. 2014;371:1039–49.CrossRefPubMedGoogle Scholar
  6. 6.
    Cancer of the pancreas—SEER Stat Fact Sheets [Internet]. [cited 2016 Jan 3]. Available from: http://seer.cancer.gov/statfacts/html/pancreas.html.
  7. 7.
    Hurria A, Togawa K, Mohile SG, Owusu C, Klepin HD, Gross CP, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol Off J Am Soc Clin Oncol. 2011;29:3457–65.CrossRefGoogle Scholar
  8. 8.
    Zeng C, Wen W, Morgans AK, Pao W, Shu X-O, Zheng W. Disparities by race, age, and sex in the improvement of survival for major cancers: results from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Program in the United States, 1990 to 2010. JAMA Oncol. 2015;1:88–96.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    He W, Zhao H, Chan W, Lopez D, Shroff RT, Giordano SH. Underuse of surgical resection among elderly patients with early-stage pancreatic cancer. Surgery. 2015;158:1226–34.CrossRefPubMedGoogle Scholar
  10. 10.
    Amin S, Lucas AL, Frucht H. Evidence for treatment and survival disparities by age in pancreatic adenocarcinoma: a population-based analysis. Pancreas. 2013;42:249–53.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Jacobson SD, Alberts SR, O’Connell MJ. Pancreatic cancer in the older patient. Oncol Williston Park N. 2001;15:926–32.Google Scholar
  12. 12.
    Parmar AD, Vargas GM, Tamirisa NP, Sheffield KM, Riall TS. Trajectory of care and use of multimodality therapy in older patients with pancreatic adenocarcinoma. Surgery. 2014;156:280–9.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Foster JA, Salinas GD, Mansell D, Williamson JC, Casebeer LL. How does older age influence oncologists’ cancer management? Oncologist. 2010;15:584–92.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Lipitz-Snyderman A, Sepkowitz KA, Elkin EB, Pinheiro LC, Sima CS, Son CH, et al. Long-term central venous catheter use and risk of infection in older adults with cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2014;32:2351–6.CrossRefGoogle Scholar
  15. 15.
    Talarico L, Chen G, Pazdur R. Enrollment of elderly patients in clinical trials for cancer drug registration: a 7-year experience by the US Food and Drug Administration. J Clin Oncol Off J Am Soc Clin Oncol. 2004;22:4626–31.CrossRefGoogle Scholar
  16. 16.
    Murthy VH, Krumholz HM, Gross CP. Participation in cancer clinical trials: race-, sex-, and age-based disparities. JAMA. 2004;291:2720–6.CrossRefPubMedGoogle Scholar
  17. 17.
    Higuera O, Ghanem I, Nasimi R, Prieto I, Koren L, Feliu J. Management of pancreatic cancer in the elderly. World J Gastroenterol. 2016;22:764–75.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Hurria A, Lichtman SM. Clinical pharmacology of cancer therapies in older adults. Br J Cancer. 2008;98:517–22.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Chen H, Cantor A, Meyer J, Beth Corcoran M, Grendys E, Cavanaugh D, et al. Can older cancer patients tolerate chemotherapy? A prospective pilot study. Cancer. 2003;97:1107–14.CrossRefPubMedGoogle Scholar
  20. 20.
    Ramjaun A, Nassif MO, Krotneva S, Huang AR, Meguerditchian AN. Improved targeting of cancer care for older patients: a systematic review of the utility of comprehensive geriatric assessment. J Geriatr Oncol. 2013;4:271–81.CrossRefPubMedGoogle Scholar
  21. 21.
    Extermann M, Hurria A. Comprehensive geriatric assessment for older patients with cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2007;25:1824–31.CrossRefGoogle Scholar
  22. 22.
    Puts MTE, Santos B, Hardt J, Monette J, Girre V, Atenafu EG, et al. An update on a systematic review of the use of geriatric assessment for older adults in oncology. Ann Oncol Off J Eur Soc Med Oncol ESMO. 2014;25:307–15.CrossRefGoogle Scholar
  23. 23.•
    Kalsi T, Babic-Illman G, Ross PJ, Maisey NR, Hughes S, Fields P, et al. The impact of comprehensive geriatric assessment interventions on tolerance to chemotherapy in older people. Br J Cancer. 2015;112:1435–44. This study showed that geriatrician-delivered geriatric assessment improves completion rates of chemotherapy, fewer treatment modifications, and decreased toxicity. CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.•
    Dale W, Hemmerich J, Kamm A, Posner MC, Matthews JB, Rothman R, et al. Geriatric assessment improves prediction of surgical outcomes in older adults undergoing pancreaticoduodenectomy: a prospective cohort study. Ann Surg. 2014;259:960–5. This is a prospective outcome study which showed that the geriatric assessment prospectively and independently predicted adverse surgical outcomes in older patients undergoing pancreaticoduodenectomy. CrossRefPubMedGoogle Scholar
  25. 25.
    Wildiers H, Heeren P, Puts M, Topinkova E, Janssen-Heijnen MLG, Extermann M, et al. International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2014;32:2595–603.CrossRefGoogle Scholar
  26. 26.
    Luciani A, Biganzoli L, Colloca G, Falci C, Castagneto B, Floriani I, et al. Estimating the risk of chemotherapy toxicity in older patients with cancer: the role of the Vulnerable Elders Survey-13 (VES-13). J Geriatr Oncol. 2015;6:272–9.CrossRefPubMedGoogle Scholar
  27. 27.
    Bellera CA, Rainfray M, Mathoulin-Pélissier S, Mertens C, Delva F, Fonck M, et al. Screening older cancer patients: first evaluation of the G-8 geriatric screening tool. Ann Oncol Off J Eur Soc Med Oncol ESMO. 2012;23:2166–72.CrossRefGoogle Scholar
  28. 28.•
    Decoster L, Van Puyvelde K, Mohile S, Wedding U, Basso U, Colloca G, et al. Screening tools for multidimensional health problems warranting a geriatric assessment in older cancer patients: an update on SIOG recommendations†. Ann Oncol Off J Eur Soc Med Oncol ESMO. 2015;26:288–300. This is the latest SIOG recommendation on screening tools for frailty in older cancer patients. It is also a good systemic review of studies comparing various screening tools with the comprehensive geriatric assessment and with each other. CrossRefGoogle Scholar
  29. 29.
    Extermann M, Boler I, Reich RR, Lyman GH, Brown RH, DeFelice J, et al. Predicting the risk of chemotherapy toxicity in older patients: the Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score. Cancer. 2012;118:3377–86.CrossRefPubMedGoogle Scholar
  30. 30.
    Goodman MD, Saif MW. Adjuvant therapy for pancreatic cancer. JOP J Pancreas. 2014;15:87–90.Google Scholar
  31. 31.
    Matsuda Y, Ishiwata T, Yachida S, Suzuki A, Hamashima Y, Hamayasu H, et al. Clinicopathological features of 15 occult and 178 clinical pancreatic ductal adenocarcinomas in 8339 autopsied elderly patients. Pancreas. 2016;45:234–40.Google Scholar
  32. 32.
    Brentnall TA. Management strategies for patients with hereditary pancreatic cancer. Curr Treat Options Oncol. 2005;6:437–45.CrossRefPubMedGoogle Scholar
  33. 33.
    Brand RE, Lerch MM, Rubinstein WS, Neoptolemos JP, Whitcomb DC, Hruban RH, et al. Advances in counselling and surveillance of patients at risk for pancreatic cancer. Gut. 2007;56:1460–9.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Riall TS, Sheffield KM, Kuo Y-F, Townsend CM, Goodwin JS. Resection benefits older adults with locoregional pancreatic cancer despite greater short-term morbidity and mortality. J Am Geriatr Soc. 2011;59:647–54.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Riall TS. What is the effect of age on pancreatic resection? Adv Surg. 2009;43:233–49.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Cameron JL, Riall TS, Coleman J, Belcher KA. One thousand consecutive pancreaticoduodenectomies. Ann Surg. 2006;244:10–5.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Cameron JL, He J. Two thousand consecutive pancreaticoduodenectomies. J Am Coll Surg. 2015;220:530–6.CrossRefPubMedGoogle Scholar
  38. 38.
    Fong Y, Blumgart LH, Fortner JG, Brennan MF. Pancreatic or liver resection for malignancy is safe and effective for the elderly. Ann Surg. 1995;222:426–34.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.•
    Turrini O, Paye F, Bachellier P, Sauvanet A, Sa Cunha A, Le Treut YP, et al. Pancreatectomy for adenocarcinoma in elderly patients: postoperative outcomes and long term results: a study of the French Surgical Association. Eur J Surg Oncol. 2013;39:171–8. Large study composing of more than 900 patients in Europe with pancreatic cancer undergoing pancreatectomy showing similar postoperative mortality and morbidity rates in patients of three age groups: <70, 70–79, and ≥80 years.CrossRefPubMedGoogle Scholar
  40. 40.
    Oliveira-Cunha M, Malde DJ, Aldouri A, Morris-Stiff G, Menon KV, Smith AM. Results of pancreatic surgery in the elderly: is age a barrier? HPB. 2013;15:24–30.CrossRefPubMedGoogle Scholar
  41. 41.
    Hayman TJ, Strom T, Springett GM, Balducci L, Hoffe SE, Meredith KL, et al. Outcomes of resected pancreatic cancer in patients age ≥70. J Gastrointest Oncol. 2015;6:498–504.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Beltrame V, Gruppo M, Pastorelli D, Pedrazzoli S, Merigliano S, Sperti C. Outcome of pancreaticoduodenectomy in octogenarians: single institution’s experience and review of the literature. J Visc Surg. 2015;152:279–84.CrossRefPubMedGoogle Scholar
  43. 43.
    Hatzaras I, Schmidt C, Klemanski D, Muscarella P, Melvin WS, Ellison EC, et al. Pancreatic resection in the octogenarian: a safe option for pancreatic malignancy. J Am Coll Surg. 2011;212:373–7.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Makary MA, Winter JM, Cameron JL, Campbell KA, Chang D, Cunningham SC, et al. Pancreaticoduodenectomy in the very elderly. J Gastrointest Surg Off J Soc Surg Aliment Tract. 2006;10:347–56.CrossRefGoogle Scholar
  45. 45.
    van der Geest LGM, Besselink MGH, van Gestel YRBM, Busch ORC, de Hingh IHJT, de Jong KP, et al. Pancreatic cancer surgery in elderly patients: balancing between short-term harm and long-term benefit. A population-based study in the Netherlands. Acta Oncol Stockh Swed. 2016;55:278–85.Google Scholar
  46. 46.
    Shah BC, Smith LM, Ullrich F, Are C. Discharge disposition after pancreatic resection for malignancy: analysis of national trends. HPB. 2012;14:201–8.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Finlayson E, Fan Z, Birkmeyer JD. Outcomes in octogenarians undergoing high-risk cancer operation: a national study. J Am Coll Surg. 2007;205:729–34.CrossRefPubMedGoogle Scholar
  48. 48.
    Paniccia A, Hosokawa P, Henderson W, Schulick RD, Edil BH, McCarter MD, et al. Characteristics of 10-year survivors of pancreatic ductal adenocarcinoma. JAMA Surg. 2015;150:701–10.CrossRefPubMedGoogle Scholar
  49. 49.
    Horowitz DP, Hsu CC, Wang J, Makary MA, Winter JM, Robinson R, et al. Adjuvant chemoradiation therapy after pancreaticoduodenectomy in elderly patients with pancreatic adenocarcinoma. Int J Radiat Oncol Biol Phys. 2011;80:1391–7.CrossRefPubMedGoogle Scholar
  50. 50.
    Frakes JM, Strom T, Springett GM, Hoffe SE, Balducci L, Hodul P, et al. Resected pancreatic cancer outcomes in the elderly. J Geriatr Oncol. 2015;6:127–32.CrossRefPubMedGoogle Scholar
  51. 51.
    Nagrial AM, Chang DK, Nguyen NQ, Johns AL, Chantrill LA, Humphris JL, et al. Adjuvant chemotherapy in elderly patients with pancreatic cancer. Br J Cancer. 2014;110:313–9.CrossRefPubMedGoogle Scholar
  52. 52.
    Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004;350:1200–10.CrossRefPubMedGoogle Scholar
  53. 53.•
    Oettle H, Neuhaus P, Hochhaus A, Hartmann JT, Gellert K, Ridwelski K, 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. This trial established that adjuvant chemotherapy with gemcitabine provides survival benefit in the adjuvant setting. CrossRefPubMedGoogle Scholar
  54. 54.
    Neoptolemos JP, Stocken DD, Bassi C, Ghaneh P, Cunningham D, Goldstein D, et al. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA. 2010;304:1073–81.CrossRefPubMedGoogle Scholar
  55. 55.•
    Neoptolemos JP, Palmer D, Ghaneh P, Valle JW, Cunningham D, Wadsley J, et al. ESPAC-4: a multicenter, international, open-label randomized controlled phase III trial of adjuvant combination chemotherapy of gemcitabine (GEM) and capecitabine (CAP) versus monotherapy gemcitabine in patients with resected pancreatic ductal adenocarcinoma. ASCO Meet Abstr. 2016;34:LBA4006. This large randomized study showed superiority of adjuvant gemcitabine with capecitabine over gemcitabine alone and may change standard of care. Google Scholar
  56. 56.
    Murakawa M, Aoyama T, Katayama Y, Asari M, Sawazaki S, Yamaoku K, et al. Safety and feasibility of S-1 adjuvant chemotherapy for pancreatic cancer in elderly patients. ASCO Meet Abstr. 2015;33:486.Google Scholar
  57. 57.
    Kalser MH, Ellenberg SS. Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg Chic Ill 1960. 1985;120:899–903.Google Scholar
  58. 58.
    Regine WF, Winter KA, Abrams RA, Safran H, Hoffman JP, Konski A, 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.CrossRefPubMedGoogle Scholar
  59. 59.•
    Valle JW, Palmer D, Jackson R, Cox T, Neoptolemos JP, Ghaneh P, 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 Off J Am Soc Clin Oncol. 2014;32:504–12. This study showed that completion of all 6 cycles of adjuvant chemotherapy was more important than timing of adjuvant therapy. CrossRefGoogle Scholar
  60. 60.
    Sultana A, Tudur Smith C, Cunningham D, Starling N, Tait D, Neoptolemos JP, et al. Systematic review, including meta-analyses, on the management of locally advanced pancreatic cancer using radiation/combined modality therapy. Br J Cancer. 2007;96:1183–90.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Krzyzanowska MK, Weeks JC, Earle CC. Treatment of locally advanced pancreatic cancer in the real world: population-based practices and effectiveness. J Clin Oncol Off J Am Soc Clin Oncol. 2003;21:3409–14.CrossRefGoogle Scholar
  62. 62.
    Morizane C, Okusaka T, Ito Y, Ueno H, Ikeda M, Takezako Y, et al. Chemoradiotherapy for locally advanced pancreatic carcinoma in elderly patients. Oncology. 2005;68:432–7.CrossRefPubMedGoogle Scholar
  63. 63.
    Loehrer PJ, Feng Y, Cardenes H, Wagner L, Brell JM, Cella D, et al. Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial. J Clin Oncol Off J Am Soc Clin Oncol. 2011;29:4105–12.CrossRefGoogle Scholar
  64. 64.•
    Hammel P, Huguet F, Van Laethem J-L, Goldstein D, Glimelius B, Artru P, et al. Comparison of chemoradiotherapy (CRT) and chemotherapy (CT) in patients with a locally advanced pancreatic cancer (LAPC) controlled after 4 months of gemcitabine with or without erlotinib: final results of the international phase III LAP 07 study. ASCO Meet Abstr. 2013;31:LBA4003. This is the largest phase III trial to date comparing chemoradiotherapy to chemotherapy alone in locally advanced disease. This study showed no survival benefit with chemoradiation. Google Scholar
  65. 65.
    Kim CH, Ling DC, Wegner RE, Flickinger JC, Heron DE, Zeh H, et al. Stereotactic body radiotherapy in the treatment of pancreatic adenocarcinoma in elderly patients. Radiat Oncol Lond Engl. 2013;8:240.CrossRefGoogle Scholar
  66. 66.
    Tozzi A, Comito T, Alongi F, Navarria P, Iftode C, Mancosu P, et al. SBRT in unresectable advanced pancreatic cancer: preliminary results of a mono-institutional experience. Radiat Oncol Lond Engl. 2013;8:148.CrossRefGoogle Scholar
  67. 67.
    Alagappan M, Pollom EL, von Eyben R, Kozak MM, Aggarwal S, Poultsides GA, et al. Albumin and neutrophil-lymphocyte ratio (NLR) predict survival in patients with pancreatic adenocarcinoma treated with SBRT. Am J Clin Oncol. 2016. doi: 10.1097/COC.0000000000000263.
  68. 68.•
    Chuong MD, Springett GM, Freilich JM, Park CK, Weber JM, Mellon EA, et al. Stereotactic body radiation therapy for locally advanced and borderline resectable pancreatic cancer is effective and well tolerated. Int J Radiat Oncol. 2013;86:516–22. This is one of the larger series on the effectiveness of SBRT in locally advanced and borderline resectable pancreatic cancer. CrossRefGoogle Scholar
  69. 69.
    Callery MP, Chang KJ, Fishman EK, Talamonti MS, William Traverso L, Linehan DC. Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement. Ann Surg Oncol. 2009;16:1727–33.CrossRefPubMedGoogle Scholar
  70. 70.
    Katz MHG, Pisters PWT, Evans DB, Sun CC, Lee JE, Fleming JB, et al. Borderline resectable pancreatic cancer: the importance of this emerging stage of disease. J Am Coll Surg. 2008;206:833–46.CrossRefPubMedGoogle Scholar
  71. 71.
    Laurence JM, Tran PD, Morarji K, Eslick GD, Lam VWT, Sandroussi C. A systematic review and meta-analysis of survival and surgical outcomes following neoadjuvant chemoradiotherapy for pancreatic cancer. J Gastrointest Surg Off J Soc Surg Aliment Tract. 2011;15:2059–69.CrossRefGoogle Scholar
  72. 72.
    Assifi MM, Lu X, Eibl G, Reber HA, Li G, Hines OJ. Neoadjuvant therapy in pancreatic adenocarcinoma: a meta-analysis of phase II trials. Surgery. 2011;150:466–73.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.•
    Miura JT, Krepline AN, George B, Ritch PS, Erickson BA, Johnston FM, et al. Use of neoadjuvant therapy in patients 75 years of age and older with pancreatic cancer. Surgery. 2015;158:1545–55. This study showed that older patients can derive similar benefits from neoadjuvant therapy compared to younger patients in resectable or borderline resectable pancreatic cancer. CrossRefPubMedGoogle Scholar
  74. 74.
    Hosein PJ, Macintyre J, Kawamura C, Maldonado JC, Ernani V, Loaiza-Bonilla A, et al. A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma. BMC Cancer. 2012;12:199.CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Christians KK, Tsai S, Mahmoud A, Ritch P, Thomas JP, Wiebe L, et al. Neoadjuvant FOLFIRINOX for borderline resectable pancreas cancer: a new treatment paradigm? Oncologist. 2014;19:266–74.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Peddi PF, Lubner S, McWilliams R, Tan BR, Picus J, Sorscher SM, et al. Multi-institutional experience with FOLFIRINOX in pancreatic adenocarcinoma. JOP J Pancreas. 2012;13:497–501.Google Scholar
  77. 77.•
    Blazer M, Wu C, Goldberg RM, Phillips G, Schmidt C, Muscarella P, et al. Neoadjuvant modified (m) FOLFIRINOX for locally advanced unresectable (LAPC) and borderline resectable (BRPC) adenocarcinoma of the pancreas. Ann Surg Oncol. 2015;22:1153–9. Although effective, FOLFIRINOX has significant toxicity. This study described the experience with a modified FOLFIRINOX regimen in the neoadjuvant setting and showed that it is an effective and well-tolerated regimen. CrossRefPubMedGoogle Scholar
  78. 78.
    Katz MHG, Shi Q, Ahmad SA, Herman JM, Marsh R de w, Collisson EA, et al. Preoperative modified FOLFIRINOX (mFOLFIRINOX) followed by chemoradiation (CRT) for borderline resectable (BLR) pancreatic cancer (PDAC): initial results from Alliance Trial A021101. ASCO Meet Abstr. 2015;33:4008.Google Scholar
  79. 79.
    Varadhachary GR, Fleming JB, Crane CH, Fogelman DR, Shroff RT, Lee JE, et al. Phase II study of preoperation mFOLFIRINOX and chemoradiation for high-risk resectable and borderline resectable pancreatic adenocarcinoma. ASCO Meet Abstr. 2015;33:362.Google Scholar
  80. 80.
    Capello M, Lee M, Wang H, Babel I, Katz MH, Fleming JB, et al. Carboxylesterase 2 as a determinant of response to irinotecan and neoadjuvant FOLFIRINOX therapy in pancreatic ductal adenocarcinoma. J Natl Cancer Inst. 2015;107:djv132.Google Scholar
  81. 81.
    Kunzmann V, Herrmann K, Bluemel C, Kapp M, Hartlapp I, Steger U. Intensified neoadjuvant chemotherapy with nab-paclitaxel plus gemcitabine followed by FOLFIRINOX in a patient with locally advanced unresectable pancreatic cancer. Case Rep Oncol. 2014;7:648–55.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Trial to investigate intensified neoadjuvant chemotherapy in locally advanced pancreatic cancer—full text view—ClinicalTrials.gov [Internet]. [cited 2016 Mar 4]. Available from: https://clinicaltrials.gov/ct2/show/NCT02125136.
  83. 83.
    Tas F, Sen F, Keskin S, Kilic L, Yildiz I. Prognostic factors in metastatic pancreatic cancer: older patients are associated with reduced overall survival. Mol Clin Oncol. 2013;1:788–92.PubMedPubMedCentralGoogle Scholar
  84. 84.
    Maréchal R, Demols A, Gay F, de Maertelaer V, Arvanitaki M, Hendlisz A, et al. Tolerance and efficacy of gemcitabine and gemcitabine-based regimens in elderly patients with advanced pancreatic cancer. Pancreas. 2008;36:e16–21.CrossRefPubMedGoogle Scholar
  85. 85.
    Aldoss IT, Tashi T, Gonsalves W, Kalaiah RK, Fang X, Silberstein P, et al. Role of chemotherapy in the very elderly patients with metastatic pancreatic cancer—a Veterans Affairs Cancer Registry analysis. J Geriatr Oncol. 2011;2:209–14.CrossRefGoogle Scholar
  86. 86.
    Burris HA, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, 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 Off J Am Soc Clin Oncol. 1997;15:2403–13.Google Scholar
  87. 87.
    Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–25.CrossRefPubMedGoogle Scholar
  88. 88.•
    Alessandretti MB, Moreira RB, Brandao EP, Gomes JR, Amarante MPF, Lino ADR, et al. Safety and efficacy of modified dose-attenuated FOLFIRINOX chemotherapy in patients over 65 years with advanced pancreatic adenocarcinoma. ASCO Meet Abstr. 2015;33:468. This study suggested that in older adults, the modified FOLFIRINOX regimen can be a reasonable option in advanced pancreatic cancer. Google Scholar
  89. 89.
    Efficacy and tolerance evaluation in FOLFIRINOX dose adjusted in elderly patients with a metastatic pancreatic cancer—full text view—ClinicalTrials.gov [Internet]. [cited 2016 Feb 15]. Available from: https://clinicaltrials.gov/ct2/show/NCT02143219.
  90. 90.••
    Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369:1691–703. This is a phase III randomized study which showed survival benefit of adding nab-paclitaxel to gemcitabine and is one of the most important recent trials, along with the FOLFIRINOX study by Conroy et al., to have changed the paradigm of treatment in advanced pancreatic cancer. CrossRefGoogle Scholar
  91. 91.
    Giordano G, Vaccaro V, Lucchini E, Musettini G, Bertocchi P, Bergamo F, et al. Nab-paclitaxel (Nab-P) and gemcitabine (G) as first-line chemotherapy (CT) in advanced pancreatic cancer (APDAC) elderly patients (pts): a “real-life” study. ASCO Meet Abstr. 2015;33:424.Google Scholar
  92. 92.
    Krishna K, Blazer MA, Wei L, Ahn DH, Wu CS-Y, Ciombor KK, et al. Modified gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer (MPC): a single-institution experience. ASCO Meet Abstr. 2015;33:366.Google Scholar
  93. 93.
    Gourgou-Bourgade S, Bascoul-Mollevi C, Desseigne F, Ychou M, Bouché O, Guimbaud R, et al. Impact of FOLFIRINOX compared with gemcitabine on quality of life in patients with metastatic pancreatic cancer: results from the PRODIGE 4/ACCORD 11 randomized trial. J Clin Oncol Off J Am Soc Clin Oncol. 2013;31:23–9.CrossRefGoogle Scholar
  94. 94.•
    Wang-Gillam A, Li C-P, Bodoky G, Dean A, Shan Y-S, Jameson G, et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet Lond Engl. 2016;387:545–57. This phase III study of 417 patients showed survival benefit of adding nanoliposomal irinotecan in combination with fluorouracil and folinic acid in patients previously treated with gemcitabine-based therapy. This study led to the approval of nanoliposomal irinotecan by the FDA for this indication.CrossRefGoogle Scholar
  95. 95.
    Portal A, Pernot S, Tougeron D, Arbaud C, Bidault AT, de la Fouchardière C, et al. Nab-paclitaxel plus gemcitabine for metastatic pancreatic adenocarcinoma after Folfirinox failure: an AGEO prospective multicentre cohort. Br J Cancer. 2015;113:989–95.CrossRefPubMedGoogle Scholar
  96. 96.
    Rivera F, Gallego J, Guillen C, Benavides M, Lopez-Martin JA, Betticher DC, et al. PANOVA: a pilot study of TTFields concomitant with gemcitabine for front-line therapy in patients with advanced pancreatic adenocarcinoma. ASCO Meet Abstr. 2016;34:269.Google Scholar
  97. 97.
    Le DT, Wang-Gillam A, Picozzi V, Greten TF, Crocenzi T, Springett G, et al. Safety and survival with GVAX pancreas prime and Listeria monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2015;33:1325–33.CrossRefGoogle Scholar
  98. 98.
    Neoadjuvant/adjuvant GVAX pancreas vaccine (with CY) with or without nivolumab trial for surgically resectable pancreatic cancer—full text view—ClinicalTrials.gov [Internet]. [cited 2016 Mar 3]. Available from: https://clinicaltrials.gov/ct2/show/NCT02451982?term=pancreatic+pd1&rank=2.
  99. 99.
    Safety study of nivolumab with nab-paclitaxel plus or minus gemcitabine in pancreatic cancer, nab-paclitaxel/carboplatin in stage IIIb/IV non-small cell lung cancer or nab-paclitaxel in recurrent metastatic breast cancer—full text view—ClinicalTrials.gov [Internet]. [cited 2016 Mar 3]. Available from: https://clinicaltrials.gov/ct2/show/NCT02309177?term=pancreatic+pd1&rank=5.
  100. 100.
    Safety and immunological effect of pembrolizumab in resectable or borderline resectable pancreatic cancer—full text view—ClinicalTrials.gov [Internet]. [cited 2016 Mar 3]. Available from: https://clinicaltrials.gov/ct2/show/NCT02305186.
  101. 101.
    WHO | WHO’s cancer pain ladder for adults [Internet]. WHO. [cited 2016 Mar 3]. Available from: http://www.who.int/cancer/palliative/painladder/en/.
  102. 102.
    Wyse JM, Carone M, Paquin SC, Usatii M, Sahai AV. Randomized, double-blind, controlled trial of early endoscopic ultrasound-guided celiac plexus neurolysis to prevent pain progression in patients with newly diagnosed, painful, inoperable pancreatic cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2011;29:3541–6.CrossRefGoogle Scholar
  103. 103.
    Maire F, Hammel P, Ponsot P, Aubert A, O’Toole D, Hentic O, et al. Long-term outcome of biliary and duodenal stents in palliative treatment of patients with unresectable adenocarcinoma of the head of pancreas. Am J Gastroenterol. 2006;101:735–42.CrossRefPubMedGoogle Scholar
  104. 104.
    Nagaraja V, Eslick GD, Cox MR. Endoscopic stenting versus operative gastrojejunostomy for malignant gastric outlet obstruction-a systematic review and meta-analysis of randomized and non-randomized trials. J Gastrointest Oncol. 2014;5:92–8.PubMedPubMedCentralGoogle Scholar
  105. 105.
    Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008;111:4902–7.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Shin Yin Lee
    • 1
  • Moussa Sissoko
    • 2
  • Kevan L. Hartshorn
    • 1
  1. 1.Section of Hematology/OncologyBoston University School of Medicine, Boston Medical CenterBostonUSA
  2. 2.Charleston Area Medical Center Cancer CenterCharlestonUSA

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