Skip to main content
Erschienen in: Drugs & Aging 3/2013

01.03.2013 | Review Article

Adjuvant Pharmacotherapy in the Management of Elderly Patients with Pancreatic Cancer

verfasst von: Raphaël Maréchal, Anne Demols, Jean-Luc Van Laethem

Erschienen in: Drugs & Aging | Ausgabe 3/2013

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat Jemal A, Siegel R, Ward E, et al. Cancer statistics 2008. CA Cancer J Clin. 2008;58(2):71–96.PubMedCrossRef Jemal A, Siegel R, Ward E, et al. Cancer statistics 2008. CA Cancer J Clin. 2008;58(2):71–96.PubMedCrossRef
2.
Zurück zum Zitat Jemal A, Siegel R, Ward E, et al. Cancer statistics 2006. CA Cancer J Clin. 2006;58(2):106–30.CrossRef Jemal A, Siegel R, Ward E, et al. Cancer statistics 2006. CA Cancer J Clin. 2006;58(2):106–30.CrossRef
4.
Zurück zum Zitat Geer RJ, Brennan MF. Prognostic indicators for survival after resection of pancreatic adenocarcinoma. Am J Surg. 1993;165(1):68–72.PubMedCrossRef Geer RJ, Brennan MF. Prognostic indicators for survival after resection of pancreatic adenocarcinoma. Am J Surg. 1993;165(1):68–72.PubMedCrossRef
5.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
6.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
7.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
8.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
9.
Zurück zum Zitat Emick DM, Riall TS, Cameron JL, et al. Hospital readmission after pancreaticoduodenectomy. J Gastrointest Surg. 2006;10(9):1243–52.PubMedCrossRef Emick DM, Riall TS, Cameron JL, et al. Hospital readmission after pancreaticoduodenectomy. J Gastrointest Surg. 2006;10(9):1243–52.PubMedCrossRef
10.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
11.
12.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
13.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
14.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
15.
Zurück zum Zitat Brozzetti S, Mazzoni G, Miccini M, et al. Surgical treatment of pancreatic head carcinoma in elderly patients. Arch Surg. 2006;141(2):137–42.PubMedCrossRef Brozzetti S, Mazzoni G, Miccini M, et al. Surgical treatment of pancreatic head carcinoma in elderly patients. Arch Surg. 2006;141(2):137–42.PubMedCrossRef
16.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
17.
Zurück zum Zitat 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.PubMed 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.PubMed
18.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
19.
Zurück zum Zitat Trede M, Schwall G, Saeger HD. Survival after pancreatoduodenectomy. 118 consecutive resections without an operative mortality. Ann Surg. 1990;211(4):447–58.PubMedCrossRef Trede M, Schwall G, Saeger HD. Survival after pancreatoduodenectomy. 118 consecutive resections without an operative mortality. Ann Surg. 1990;211(4):447–58.PubMedCrossRef
20.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
21.
Zurück zum Zitat 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).CrossRef 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).CrossRef
22.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
23.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
24.
Zurück zum Zitat 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. 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.
25.
Zurück zum Zitat 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.CrossRef 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.CrossRef
26.
Zurück zum Zitat 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).PubMedCrossRef 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).PubMedCrossRef
27.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
28.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
29.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
30.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
31.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
32.
Zurück zum Zitat 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. 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.
34.
Zurück zum Zitat 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. 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.
35.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
36.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
37.
Zurück zum Zitat Schwartz JB. Race but not age affects erythromycin breath test results in older hypertensive men. J Clin Pharmacol. 2001;41(3):324–9.PubMedCrossRef Schwartz JB. Race but not age affects erythromycin breath test results in older hypertensive men. J Clin Pharmacol. 2001;41(3):324–9.PubMedCrossRef
38.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
39.
Zurück zum Zitat Evans WE, McLeod HL. Pharmacogenomics—drug disposition, drug targets, and side effects. N Engl J Med. 2003;348(6):538–49.PubMedCrossRef Evans WE, McLeod HL. Pharmacogenomics—drug disposition, drug targets, and side effects. N Engl J Med. 2003;348(6):538–49.PubMedCrossRef
40.
Zurück zum Zitat Flockhart DA, Rae JM. Cytochrome P450 3A pharmacogenetics: the road that needs travelled. Pharmacogenomics J. 2003;3(1):3–5.PubMedCrossRef Flockhart DA, Rae JM. Cytochrome P450 3A pharmacogenetics: the road that needs travelled. Pharmacogenomics J. 2003;3(1):3–5.PubMedCrossRef
41.
Zurück zum Zitat 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.PubMed 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.PubMed
42.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
43.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
44.
Zurück zum Zitat 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.PubMed 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.PubMed
45.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
46.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
47.
Zurück zum Zitat Morizane C, Okusaka T, Ito Y, et al. Chemoradiotherapy for locally advanced pancreatic carcinoma in elderly patients. Oncology. 2005;68(4–6):432–7.PubMedCrossRef Morizane C, Okusaka T, Ito Y, et al. Chemoradiotherapy for locally advanced pancreatic carcinoma in elderly patients. Oncology. 2005;68(4–6):432–7.PubMedCrossRef
48.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
49.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
50.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
51.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
52.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
53.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
54.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
55.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
56.
Zurück zum Zitat 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.CrossRef 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.CrossRef
57.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
58.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
59.
Zurück zum Zitat 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.PubMed 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.PubMed
60.
Zurück zum Zitat 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.PubMed 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.PubMed
61.
Zurück zum Zitat Huang P, Plunkett W. Induction of apoptosis by gemcitabine. Sem Oncol. 1995;22(4 Suppl 11):19–25. Huang P, Plunkett W. Induction of apoptosis by gemcitabine. Sem Oncol. 1995;22(4 Suppl 11):19–25.
62.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
63.
Zurück zum Zitat Plunkett W, Huang P, Searcy CE, et al. Gemcitabine: preclinical pharmacology and mechanisms of action. Semin Oncol. 1996;23(5 Suppl 10):3–15.PubMed Plunkett W, Huang P, Searcy CE, et al. Gemcitabine: preclinical pharmacology and mechanisms of action. Semin Oncol. 1996;23(5 Suppl 10):3–15.PubMed
64.
Zurück zum Zitat 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.PubMed 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.PubMed
65.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
66.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
67.
Zurück zum Zitat Galmarini CM. Correlation of hENT1 expression and function with gemcitabine cytotoxicity in mantle cell lymphoma lines and clinical samples. Haematologica. 2006;91(7):866B.PubMed Galmarini CM. Correlation of hENT1 expression and function with gemcitabine cytotoxicity in mantle cell lymphoma lines and clinical samples. Haematologica. 2006;91(7):866B.PubMed
68.
Zurück zum Zitat 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.PubMed 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.PubMed
69.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
70.
Zurück zum Zitat 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.PubMed 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.PubMed
71.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
72.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
73.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
74.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
75.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
76.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
77.
Zurück zum Zitat 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.CrossRef 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.CrossRef
78.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
79.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
80.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
81.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
82.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
83.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
84.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
85.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
86.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
87.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
88.
Zurück zum Zitat Extermann M. Geriatric oncology: an overview of progresses and challenges. Cancer Res Treat. 2010;42(2):61–8.PubMedCrossRef Extermann M. Geriatric oncology: an overview of progresses and challenges. Cancer Res Treat. 2010;42(2):61–8.PubMedCrossRef
Metadaten
Titel
Adjuvant Pharmacotherapy in the Management of Elderly Patients with Pancreatic Cancer
verfasst von
Raphaël Maréchal
Anne Demols
Jean-Luc Van Laethem
Publikationsdatum
01.03.2013
Verlag
Springer International Publishing AG
Erschienen in
Drugs & Aging / Ausgabe 3/2013
Print ISSN: 1170-229X
Elektronische ISSN: 1179-1969
DOI
https://doi.org/10.1007/s40266-013-0049-0

Weitere Artikel der Ausgabe 3/2013

Drugs & Aging 3/2013 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Echinokokkose medikamentös behandeln oder operieren?

06.05.2024 DCK 2024 Kongressbericht

Die Therapie von Echinokokkosen sollte immer in spezialisierten Zentren erfolgen. Eine symptomlose Echinokokkose kann – egal ob von Hunde- oder Fuchsbandwurm ausgelöst – konservativ erfolgen. Wenn eine Op. nötig ist, kann es sinnvoll sein, vorher Zysten zu leeren und zu desinfizieren. 

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Proximale Humerusfraktur: Auch 100-Jährige operieren?

01.05.2024 DCK 2024 Kongressbericht

Mit dem demographischen Wandel versorgt auch die Chirurgie immer mehr betagte Menschen. Von Entwicklungen wie Fast-Track können auch ältere Menschen profitieren und bei proximaler Humerusfraktur können selbst manche 100-Jährige noch sicher operiert werden.

Die „Zehn Gebote“ des Endokarditis-Managements

30.04.2024 Endokarditis Leitlinie kompakt

Worauf kommt es beim Management von Personen mit infektiöser Endokarditis an? Eine Kardiologin und ein Kardiologe fassen die zehn wichtigsten Punkte der neuen ESC-Leitlinie zusammen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.