Drugs & Aging

, Volume 30, Issue 3, pp 155–165 | Cite as

Adjuvant Pharmacotherapy in the Management of Elderly Patients with Pancreatic Cancer

  • Raphaël Maréchal
  • Anne Demols
  • Jean-Luc Van Laethem
Review Article

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the fourth or fifth leading cause of death from cancer in Western industrialized countries. Surgical resection is the only chance of cure, but only 15–20 % of cases are potentially resectable at presentation, and despite complete resection, the overall prognosis remains relatively poor. Adjuvant therapy has modestly improved cure rates. The majority of patients with pancreatic cancer are over the age of 65 years. But this age group is underrepresented within clinical trials, and it is unknown whether older patients achieve similar results to younger ones in terms of survival and treatment tolerance. In addition, there are no clinical trials dedicated to the elderly. Retrospective studies coming from the non-resectable setting provide some understanding on outcomes in older patients with PDAC. To date, we can reasonably argue that selected elderly patients with PDAC can benefit from curative surgery and postoperative chemotherapy as do their younger counterparts, without a significant increase in morbidity and mortality. Gemcitabine should be preferred to 5-fluorouracil on the basis of a better risk–benefit balance.

References

  1. 1.
    Jemal A, Siegel R, Ward E, et al. Cancer statistics 2008. CA Cancer J Clin. 2008;58(2):71–96.PubMedCrossRefGoogle Scholar
  2. 2.
    Jemal A, Siegel R, Ward E, et al. Cancer statistics 2006. CA Cancer J Clin. 2006;58(2):106–30.CrossRefGoogle Scholar
  3. 3.
    Shaib YH, Parila JA, El-Serag HB. The epidemiology of pancreatic cancer in the United States: changes below the surface. Medscape. http://www.medscape.com/viewarticle/537123-3. Accessed 2 Sep 2008.
  4. 4.
    Geer RJ, Brennan MF. Prognostic indicators for survival after resection of pancreatic adenocarcinoma. Am J Surg. 1993;165(1):68–72.PubMedCrossRefGoogle Scholar
  5. 5.
    Kennedy EP, Rosato EL, Sauter PK, et al. Initiation of a critical pathway for pancreaticoduodenectomy at an academic institution—the first step in multidisciplinary team building. J Am Coll Surg. 2007;204(5):917–23.PubMedCrossRefGoogle Scholar
  6. 6.
    Porter GA, Pisters PW, Mansyur C, et al. Cost and utilization impact of a clinical pathway for patients undergoing pancreaticoduodenectomy. Ann Surg Oncol. 2000;7(7):484–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Sohn TA, Yeo CJ, Cameron JL, et al. Resected adenocarcinoma of the pancreas—616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg. 2000;4(6):567–79.PubMedCrossRefGoogle Scholar
  8. 8.
    Balcom JH, Rattner DW, Warshaw AL, et al. Ten-year experience with 733 pancreatic resections: changing indications, older patients, and decreasing length of hospitalization. Arch Surg. 2001;136(4):391–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Emick DM, Riall TS, Cameron JL, et al. Hospital readmission after pancreaticoduodenectomy. J Gastrointest Surg. 2006;10(9):1243–52.PubMedCrossRefGoogle Scholar
  10. 10.
    Winter JM, Cameron JL, Campbell KA, et al. 1,423 pancreaticoduodenectomies for pancreatic cancer: a single-institution experience. J Gastrointest Surg. 2006;10(9):1199–210.PubMedCrossRefGoogle Scholar
  11. 11.
    Riall TS. What is the effect of age on pancreatic resection? Adv Surg. 2009;43:233–49.PubMedCrossRefGoogle Scholar
  12. 12.
    Riall TS, Sheffield KM, Kuo YF, Townsend CM Jr, 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.PubMedCrossRefGoogle Scholar
  13. 13.
    Muscari F, Suc B, Kirzin S, et al. Risk factors for mortality and intra-abdominal complications after pancreatoduodenectomy: multivariate analysis in 300 patients. Surgery. 2006;139(5):591–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Lightner AM, Glasgow RE, Jordan TH, Krassner AD, Way LW, Mulvihill SJ, Kirkwood KS. Pancreatic resection in the elderly. J Am Coll Surg. 2004;198(5):697–706.PubMedCrossRefGoogle Scholar
  15. 15.
    Brozzetti S, Mazzoni G, Miccini M, et al. Surgical treatment of pancreatic head carcinoma in elderly patients. Arch Surg. 2006;141(2):137–42.PubMedCrossRefGoogle Scholar
  16. 16.
    Yermilov I, Bentrem D, Sekeris E, et al. Readmissions following pancreaticoduodenectomy for pancreas cancer: a population-based appraisal. Ann Surg Oncol. 2009;16(3):554–61.PubMedCrossRefGoogle Scholar
  17. 17.
    Ouaïssi M, Sielezneff I, Pirrò N, et al. Pancreatic cancer and pancreaticoduodenectomy in elderly patient: morbidity and mortality are increased. Is it the real life? Hepatogastroenterology. 2008;55(88):2242–6.PubMedGoogle Scholar
  18. 18.
    Rubenstein LZ, Josephson KR, Wieland GD, English PA, Sayre JA, Kane RL. Effectiveness of a geriatric evaluation unit. A randomized clinical trial. N Engl J Med. 1984;311(26):1664–70.PubMedCrossRefGoogle Scholar
  19. 19.
    Trede M, Schwall G, Saeger HD. Survival after pancreatoduodenectomy. 118 consecutive resections without an operative mortality. Ann Surg. 1990;211(4):447–58.PubMedCrossRefGoogle Scholar
  20. 20.
    Bakkevold KE, Arnesjø B, Dahl O, Kambestad B. 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. 1993;29A(5):698–703.PubMedCrossRefGoogle Scholar
  21. 21.
    Tsao JI, Rossi RL, Lowell JA. Pylorus-preserving pancreatoduodenectomy. Is it an adequate cancer operation. Arch Surg. 1994;129(11):1164. (Erratum in: Arch Surg 1994 Nov;129(11):1164).CrossRefGoogle Scholar
  22. 22.
    Yeo CJ, Cameron JL, Lillemoe KD, et al. Pancreaticoduodenectomy for cancer of the head of the pancreas. 201 patients. Ann Surg. 1995;221(6):721–31.PubMedCrossRefGoogle Scholar
  23. 23.
    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(3):267–77.PubMedCrossRefGoogle Scholar
  24. 24.
    Neuhaus P, Riess H, Post S, et al. CONKO-001: final results of the randomized, prospective, multicenter phase III trial of adjuvant chemotherapy with gemcitabine versus observation in patients with resected pancreatic cancer (PC). J Clin Oncol 2008;26(May 20 suppl):abstr LBA4504.Google Scholar
  25. 25.
    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. AMA. 2010;304(10):1073–81.CrossRefGoogle Scholar
  26. 26.
    Kalser MH, Ellenberg SS. Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg. 1985;120(8):899–903. (Erratum in: Arch Surg 1986 Sep;121(9):1045).PubMedCrossRefGoogle Scholar
  27. 27.
    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(6):776–82.PubMedCrossRefGoogle Scholar
  28. 28.
    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(9):1019–26.PubMedCrossRefGoogle Scholar
  29. 29.
    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(12):1200–10.PubMedCrossRefGoogle Scholar
  30. 30.
    Sawhney R, Sehl M, Naeim A. Physiologic aspects of aging: impact on cancer management and decision making, part I. Cancer J. 2005;11(6):449–60.PubMedCrossRefGoogle Scholar
  31. 31.
    Sehl M, Sawhney R, Naeim A. Physiologic aspects of aging: impact on cancer management and decision making, part II. Cancer J. 2005;11(6):461–73.PubMedCrossRefGoogle Scholar
  32. 32.
    Duthie ED. Physiology of aging: relevance to symptom perception and treatment tolerance. In: Balducci L, Lyman GH, Ershler WB, et al., editors. Comprehensive geriatric oncology. 2nd ed. London: Taylor & Francis; 2004.Google Scholar
  33. 33.
    Vestal RE. Aging and pharmacology. Cancer. 1997;80(7):1302–10.PubMedCrossRefGoogle Scholar
  34. 34.
    Avorn J, Gurwitz JH. Principles of pharmacology. In: Cassel CK, Cohen HJ, Larson EB, et al., editors. Geriatric Medicine. 3rd ed. New York: Springer; 1996.Google Scholar
  35. 35.
    Baker SD, van Schaik RH, Rivory LP, et al. Factors affecting cytochrome P-450 3A activity in cancer patients. Clin Cancer Res. 2004;10(24):8341–50.PubMedCrossRefGoogle Scholar
  36. 36.
    Hunt CM, Westerkam WR, Stave GM. Effect of age and gender on the activity of human hepatic CYP3A. Biochem Pharmacol. 1992;44(2):275–83.PubMedCrossRefGoogle Scholar
  37. 37.
    Schwartz JB. Race but not age affects erythromycin breath test results in older hypertensive men. J Clin Pharmacol. 2001;41(3):324–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Sotaniemi EA, Arranto AJ, Pelkonen O, et al. Age and cytochrome P450-linked drug metabolism in humans: an analysis of 226 subjects with equal histopathologic conditions. Clin Pharmacol Ther. 1997;61(3):331–9.PubMedCrossRefGoogle Scholar
  39. 39.
    Evans WE, McLeod HL. Pharmacogenomics—drug disposition, drug targets, and side effects. N Engl J Med. 2003;348(6):538–49.PubMedCrossRefGoogle Scholar
  40. 40.
    Flockhart DA, Rae JM. Cytochrome P450 3A pharmacogenetics: the road that needs travelled. Pharmacogenomics J. 2003;3(1):3–5.PubMedCrossRefGoogle Scholar
  41. 41.
    Milano G, Etienne MC, Cassuto-Viguier E, et al. Influence of sex and age on fluorouracil clearance. J Clin Oncol. 1992;10(7):1171–5.PubMedGoogle Scholar
  42. 42.
    Stein BN, Petrelli NJ, Douglass HO, et al. Age and sex are independent predictors of 5-fluorouracil toxicity. Analysis of a large scale phase III trial. Cancer. 1995;75(1):11–7.PubMedCrossRefGoogle Scholar
  43. 43.
    Sloan JA, Goldberg RM, Sargent DJ, et al. Women experience greater toxicity with fluorouracil-based chemotherapy for colorectal cancer. J Clin Oncol. 2002;20(6):1491–8.PubMedCrossRefGoogle Scholar
  44. 44.
    Popescu RA, Norman A, Ross PJ, et al. Adjuvant or palliative chemotherapy for colorectal cancer in patients 70 years or older. J Clin Oncol. 1999;17(8):2412–8.PubMedGoogle Scholar
  45. 45.
    Chiara S, Nobile MT, Vincenti M, et al. Advanced colorectal cancer in the elderly: results of consecutive trials with 5-fluorouracil-based chemotherapy. Cancer Chemother Pharmacol. 1998;42:336–40.PubMedCrossRefGoogle Scholar
  46. 46.
    Sargent DJ, Goldberg RM, Jacobson SD, et al. A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients. N Engl J Med. 2001;345(15):1091–7.PubMedCrossRefGoogle Scholar
  47. 47.
    Morizane C, Okusaka T, Ito Y, et al. Chemoradiotherapy for locally advanced pancreatic carcinoma in elderly patients. Oncology. 2005;68(4–6):432–7.PubMedCrossRefGoogle Scholar
  48. 48.
    Miyamoto DT, Mamon HJ, Ryan DP, et al. Outcomes and tolerability of chemoradiation therapy for pancreatic cancer patients aged 75 years or older. Int J Radiat Oncol Biol Phys. 2010;77(4):1171–7.PubMedCrossRefGoogle Scholar
  49. 49.
    Vickers MM, Powell ED, Asmis TR, et al. Comorbidity, age and overall survival in patients with advanced pancreatic cancer—results from NCIC CTG PA.3: a phase III trial of gemcitabine plus erlotinib or placebo. Eur J Cancer. 2012;48(10):1434–42.PubMedCrossRefGoogle Scholar
  50. 50.
    Nakai Y, Isayama H, Sasaki T, et al. Comorbidity, not age, is prognostic in patients with advanced pancreatic cancer receiving gemcitabine-based chemotherapy. Crit Rev Oncol Hematol. 2011;78(3):252–9.PubMedCrossRefGoogle Scholar
  51. 51.
    Maréchal R, Demols A, Gay F, et al. Tolerance and efficacy of gemcitabine and gemcitabine-based regimens in elderly patients with advanced pancreatic cancer. Pancreas. 2008;36(3):e16–21.PubMedCrossRefGoogle Scholar
  52. 52.
    Locher C, Fabre-Guillevin E, Brunetti F, et al. Fixed-dose rate gemcitabine in elderly patients with advanced pancreatic cancer: an observational study. Crit Rev Oncol Hematol. 2008;68(2):178–82.PubMedCrossRefGoogle Scholar
  53. 53.
    Hentic O, Dreyer C, Rebours V, Zappa M, Lévy P, Raymond E, Ruszniewski P, Hammel P. Gemcitabine in elderly patients with advanced pancreatic cancer. World J Gastroenterol. 2011;17(30):3497–502.PubMedCrossRefGoogle Scholar
  54. 54.
    Gianni L, Eiermann W, Semiglazov V, et al. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet. 2010;375(9712):377–84.PubMedCrossRefGoogle Scholar
  55. 55.
    Lièvre A, Bachet JB, Boige V, et al. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol. 2008;26(3):374–9.PubMedCrossRefGoogle Scholar
  56. 56.
    Mackey JR, Baldwin SA, Young JD, Cass CE. Nucleoside transport and its significance for anticancer drug resistance. Drug Resist Update. 1998;1(5):310–24.CrossRefGoogle Scholar
  57. 57.
    Mackey JR, Yao SY, Smith KM, et al. Gemcitabine transport in Xenophus oocytes expressing recombinant plasma membrane mammalian nucleoside transporters. J Natl Cancer Inst. 1999;91(21):1876–81.PubMedCrossRefGoogle Scholar
  58. 58.
    Ritzel MW, Ng AM, Yao SY, et al. Recent molecular advances in studies of the concentrative nucleoside transporter (CNT): identification and characterization of novel human and mouse proteins (hCNT3 and mCNT3) broadly selective for purine and pyrimidine nucleosides. Mol Membr Biol. 2001;18(1):65–72.PubMedCrossRefGoogle Scholar
  59. 59.
    Mackey JR, Mani RS, Selner M, et al. Functional nucleoside transporters are required for gemcitabine influx and manifestation of toxicity in cancer cell lines. Cancer Res. 1998;58(19):4349–57.PubMedGoogle Scholar
  60. 60.
    Garcia-Manteiga J, Molina-Arcas M, Casado FJ, et al. Nucleoside transporter profiles in human pancreatic cancer cells: role of hCNT1 in 2′,2′-difluorodeoxycitidine-induced cytotoxicity. Clin Cancer Res. 2003;9(13):5000–8.PubMedGoogle Scholar
  61. 61.
    Huang P, Plunkett W. Induction of apoptosis by gemcitabine. Sem Oncol. 1995;22(4 Suppl 11):19–25.Google Scholar
  62. 62.
    Ruiz van Haperen VW, Veerman G, Vermorken JB, et al. 2′,2′-difluoro-deoxycitidine (gemcitabine) incorporation into RNA and DNA of tumour cell lines. Biochem Pharmacol. 1993;46(4):762–6.PubMedCrossRefGoogle Scholar
  63. 63.
    Plunkett W, Huang P, Searcy CE, et al. Gemcitabine: preclinical pharmacology and mechanisms of action. Semin Oncol. 1996;23(5 Suppl 10):3–15.PubMedGoogle Scholar
  64. 64.
    Mori R, Ishikawa T, Ichikawa Y, et al. Human equilibrative nucleoside transporter 1 is associated with the chemosensitivity of gemcitabine in human pancreatic adenocarcinoma and biliary tract carcinoma cells. Oncol Rep. 2007;17(5):1201–5.PubMedGoogle Scholar
  65. 65.
    Nakano Y, Tanno S, Koizumi K, et al. Gemcitabine chemoresistance and molecular markers associated with gemcitabine transport and metabolism in human pancreatic cancer cells. Br J Cancer. 2007;96(3):457–63.PubMedCrossRefGoogle Scholar
  66. 66.
    Achiwa H, Oguri T, Sato S, et al. Determinants of sensitivity and resistance to gemcitabine: the roles of human equilibrative nucleoside transporter 1 and deoxycytidine kinase in non-small cell lung cancer. Cancer Sci. 2004;95(9):753–7.PubMedCrossRefGoogle Scholar
  67. 67.
    Galmarini CM. Correlation of hENT1 expression and function with gemcitabine cytotoxicity in mantle cell lymphoma lines and clinical samples. Haematologica. 2006;91(7):866B.PubMedGoogle Scholar
  68. 68.
    Kroep JR, Loves WJ, van der Wilt CL, et al. Pretreatment deoxycytidine kinase levels predict in vivo gemcitabine sensitivity. Mol Cancer Ther. 2002;1(6):371–6.PubMedGoogle Scholar
  69. 69.
    Sebastiani V, Ricci F, Rubio-Viquiera B, et al. Immunohistochemical and genetic evaluation of deoxycytidine kinase in pancreatic cancer: relationship to molecular mechanisms of gemcitabine resistance and survival. Clin Cancer Res. 2006;12(8):2492–7.PubMedCrossRefGoogle Scholar
  70. 70.
    Cao MY, Lee Y, Feng NP, et al. Adenovirus-mediated ribonucleotide reductase R1 gene therapy of human colon adenocarcinoma. Clin Cancer Res. 2003;9(12):4553–61.PubMedGoogle Scholar
  71. 71.
    Rosell R, Danenberg KD, Alberola V, et al. Ribonucleotide reductase messenger RNA expression and survival in gemcitabine/cisplatin-treated advanced non-small cell lung cancer patients. Clin Cancer Res. 2004;10(4):1318–25.PubMedCrossRefGoogle Scholar
  72. 72.
    Bepler G, Kusmartseva I, Sharma S, et al. RRM1 modulated in vitro and in vivo efficacy of gemcitabine and platinum in non-small-cell lung cancer. J Clin Oncol. 2006;24(29):4731–7.PubMedCrossRefGoogle Scholar
  73. 73.
    Bergman AM, Eijk PP, Ruiz van Haperen VW, et al. In vivo induction of resistance to gemcitabine results in increased expression of ribonucleotide reductase subunit M1 as the major determinant. Cancer Res. 2005;65(20):9510–6.PubMedCrossRefGoogle Scholar
  74. 74.
    Nakahira S, Nakamori S, Tsujie M, et al. Involvement of ribonucleotide reductase M1 subunit overexpression in gemcitabine resistance of human pancreatic cancer. Int J Cancer. 2007;120(6):1355–63.PubMedCrossRefGoogle Scholar
  75. 75.
    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(1):187–95.PubMedCrossRefGoogle Scholar
  76. 76.
    Maréchal R, Mackey JR, Lai R, et al. Deoxycitidine kinase is associated with prolonged survival after adjuvant gemcitabine for resected pancreatic adenocarcinoma. Cancer. 2010;116(22):5200–6.PubMedCrossRefGoogle Scholar
  77. 77.
    Fukunga AK, Marsh S, Murry DJ, Hurley TD, McLeod HL. Identification and analysis of single-nucleotide polymorphisms in the gemcitabine pharmacologic pathway. Pharmacogenomics J. 2004;4:307–14.CrossRefGoogle Scholar
  78. 78.
    Tanaka M, Javle M, Dong X, et al. Gemcitabine metabolism and transporter gene polymorphisms are associated with drug toxicity and efficacy in patients with locally advanced pancreatic cancer. Cancer. 2010;116(22):5325–35.PubMedCrossRefGoogle Scholar
  79. 79.
    Okazaki T, Javle M, Tanaka M, Abbruzzese JL, Li D. Single nucleotide polymorphisms and gemcitabine metabolic genes and pancreatic cancer survival and drug toxicity. Clin Cancer Res. 2010;16(1):320–9.PubMedCrossRefGoogle Scholar
  80. 80.
    Kim SR, Saito Y, Maekawa K, et al. Thirty novel genetic variations in the SLC29A1 gene encoding human equilibrative nucleoside transporter 1 (hENT1). Drug Metab Pharmacokinet. 2006;21(3):248–56.PubMedCrossRefGoogle Scholar
  81. 81.
    Osato DH, Huang CC, Kawamoto M, et al. Fonctional characterization in yeast of genetic variants in the human equilibrative nucleoside transporter, ENT1. Pharmacogenetics. 2003;13(5):297–301.PubMedCrossRefGoogle Scholar
  82. 82.
    Popat S, Matakidou A, Houlston RS. Thymidylate synthase expression and prognosis in colorectal cancer: a systematic review and meta-analysis. J Clin Oncol. 2004;22:529–36.PubMedCrossRefGoogle Scholar
  83. 83.
    Boige V, Mendiboure J, Pignon JP, et al. Pharmacogenetic assessment of toxicity and outcome in patients with metastatic colorectal cancer treated with LV5FU2, FOLFOX, and FOLFIRI: FFCD 2000–05. J Clin Oncol. 2010;28(15):2556–64.PubMedCrossRefGoogle Scholar
  84. 84.
    Locker GY, Hamilton S, Harris J, et al. ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol. 2006;24(33):5313–27.PubMedCrossRefGoogle Scholar
  85. 85.
    Grothey A, Sargent D, Goldberg RM, Schmoll HJ. Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan, and oxaliplatin in the course of treatment. J Clin Oncol. 2004;22(7):1209–14.PubMedCrossRefGoogle Scholar
  86. 86.
    Lurje G, Manegold PC, Ning Y, Pohl A, Zhang W, Lenz HJ. Thymidylate synthase gene variations: predictive and prognostic markers. Mol Cancer Ther. 2009;8(5):1000–7.PubMedCrossRefGoogle Scholar
  87. 87.
    Kleibl Z, Fidlerova J, Kleiblova P, et al. Influence of dihydropyrimidine dehydrogenase gene (DPYD) coding sequence variants on the development of fluoropyrimidine-related toxicity in patients with high-grade toxicity and patients with excellent tolerance of fluoropyrimidine-based chemotherapy. Neoplasma. 2009;56:303–16.PubMedCrossRefGoogle Scholar
  88. 88.
    Extermann M. Geriatric oncology: an overview of progresses and challenges. Cancer Res Treat. 2010;42(2):61–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  • Raphaël Maréchal
    • 1
  • Anne Demols
    • 1
  • Jean-Luc Van Laethem
    • 1
  1. 1.Department of Gastroenterology, GI Cancer Unit, Erasme University HospitalUniversité Libre de BruxellesBrusselsBelgium

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