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Erschienen in: Journal of Gastrointestinal Cancer 2/2017

16.03.2017 | Review Article

Systemic Combination Chemotherapy in Elderly Pancreatic Cancer: a Review

verfasst von: Gwenalyn Garcia, Marcel Odaimi

Erschienen in: Journal of Gastrointestinal Cancer | Ausgabe 2/2017

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Abstract

Purpose

In recent years, significant progress in survival has been achieved using systemic combination chemotherapy in patients with pancreatic cancer. However, the elderly are largely underrepresented in clinical trials, and gains made from these may not necessarily apply to this important subgroup of patients. We review the currently available data regarding contemporary combination chemotherapy regimens, including FOLFIRINOX, gemcitabine plus nab-paclitaxel, nanoliposomal irinotecan plus 5-fluorouracil and leucovorin, and gemcitabine plus capecitabine, in elderly pancreatic cancer patients.

Methods

We performed a search of Pubmed using the terms “pancreatic cancer”, “elderly”, “FOLFIRINOX”, “gemcitabine”, “nab-paclitaxel”, “capecitabine”, and “nanoliposomal irinotecan” and included articles investigating the use of combination chemotherapy in the elderly with pancreatic adenocarcinoma. Relevant abstracts from American Society of Clinical Oncology and European Society of Medical Oncology meetings were included.

Results

Current clinical evidence and experience suggests that relatively fit elderly pancreatic cancer patients may derive significant benefit from contemporary combination chemotherapy regimens. Strategies to improve tolerability without decreasing efficacy include dose reduction, schedule modification, and growth factor support. Phase III clinical trials are ongoing to determine the optimal use of combination chemotherapy regimens in elderly patients with pancreatic cancer.

Conclusion

Identifying elderly patients who will benefit from combination chemotherapy for pancreatic cancer remains a significant clinical challenge. An assessment of medical comorbidities and functional status plays a key role in determining fitness for intensive chemotherapeutic regimens in this important subset of patients.
Literatur
2.
Zurück zum Zitat Sohal DP, Mangu PB, Khoraria AA, et al. Metastatic pancreatic cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2016;2784–96. Sohal DP, Mangu PB, Khoraria AA, et al. Metastatic pancreatic cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2016;2784–96.
3.
Zurück zum Zitat Neoptolemos JP, Palmer D, Ghaneh P, et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2017. Neoptolemos JP, Palmer D, Ghaneh P, et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2017.
4.
Zurück zum Zitat King JC, Zenati M, Steve J, et al. Deviations from expected treatment of pancreatic cancer in octogenarians: analysis of patient and surgeon factors. Ann Surg Oncol. 2016;23:4149–55. King JC, Zenati M, Steve J, et al. Deviations from expected treatment of pancreatic cancer in octogenarians: analysis of patient and surgeon factors. Ann Surg Oncol. 2016;23:4149–55.
5.
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;36:316–21. 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;36:316–21.
6.
Zurück zum Zitat Nagrial AM, Chang DK, Nguyen NQ, et al. Adjuvant chemotherapy in elderly patients with pancreatic cancer. Br J Cancer. 2014;110:313–9. Nagrial AM, Chang DK, Nguyen NQ, et al. Adjuvant chemotherapy in elderly patients with pancreatic cancer. Br J Cancer. 2014;110:313–9.
7.
Zurück zum Zitat Miura JT, Krepline AN, George B, et al. Use of neoadjuvant therapy in patients 75 years of age and older with pancreatic cancer. Surgery. 2015;158:1545–55. Miura JT, Krepline AN, George B, et al. Use of neoadjuvant therapy in patients 75 years of age and older with pancreatic cancer. Surgery. 2015;158:1545–55.
8.
Zurück zum Zitat Cooper AB, Holmes HM, des Bordes JKA, et al. Role of neoadjuvant therapy in the multimodality treatment of older patients with pancreatic cancer. J Am Coll Surg. 2014;219:111–21. Cooper AB, Holmes HM, des Bordes JKA, et al. Role of neoadjuvant therapy in the multimodality treatment of older patients with pancreatic cancer. J Am Coll Surg. 2014;219:111–21.
9.
Zurück zum Zitat Berger AK, Abel U, Komander, C, Harig S, Jäger D, Springfield C. Chemotherapy for advanced pancreatic adenocarcinoma in elderly patients (≥70 years of age): a retrospective cohort study at the National Center for Tumor Diseases Heidelberg. Pancreatology. 2014;14:211–5. Berger AK, Abel U, Komander, C, Harig S, Jäger D, Springfield C. Chemotherapy for advanced pancreatic adenocarcinoma in elderly patients (≥70 years of age): a retrospective cohort study at the National Center for Tumor Diseases Heidelberg. Pancreatology. 2014;14:211–5.
10.
Zurück zum Zitat Wildiers H, Highley MS, de Bruijn EA, van Oosterom AT. Pharmacology of anticancer drugs in the elderly population. Clin Pharmacokinet. 2003;42;1213–42. Wildiers H, Highley MS, de Bruijn EA, van Oosterom AT. Pharmacology of anticancer drugs in the elderly population. Clin Pharmacokinet. 2003;42;1213–42.
11.
Zurück zum Zitat Crombag MBS, Joerger M, Thürlimann B, Schellens JHM, Beijnen JH, Huietma ADR. Pharmacokinetics of selected anticancer drugs in elderly cancer patients: focus on breast cancer. Cancers (Basel). 2016. Crombag MBS, Joerger M, Thürlimann B, Schellens JHM, Beijnen JH, Huietma ADR. Pharmacokinetics of selected anticancer drugs in elderly cancer patients: focus on breast cancer. Cancers (Basel). 2016.
12.
Zurück zum Zitat Lichtman SM, Wildiers H, Chatelut E, et al. International Society of Geriatric Oncology Chemotherapy Taskforce: evaluation of chemotherapy in older patients—an analysis of the medical literature. J Clin Oncol. 2007;25:1832–43. Lichtman SM, Wildiers H, Chatelut E, et al. International Society of Geriatric Oncology Chemotherapy Taskforce: evaluation of chemotherapy in older patients—an analysis of the medical literature. J Clin Oncol. 2007;25:1832–43.
13.
Zurück zum Zitat Lichtman SM, Boparai MK. Anticancer drug therapy in the older cancer patient: pharmacology and polypharmacy. Curr Treat Options Oncol. 2008;9:191–203. Lichtman SM, Boparai MK. Anticancer drug therapy in the older cancer patient: pharmacology and polypharmacy. Curr Treat Options Oncol. 2008;9:191–203.
18.
Zurück zum Zitat Caudle KE, Thorn CF, Klein TE, et al. Clinical pharmacogenetics implementation consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing. Clin Pharmacol Ther. 2013;94:640–5. Caudle KE, Thorn CF, Klein TE, et al. Clinical pharmacogenetics implementation consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing. Clin Pharmacol Ther. 2013;94:640–5.
19.
Zurück zum Zitat Ezzeldin H, Diasio R. Dihydropyrimidine dehydrogenase deficiency, a pharmacogenetic syndrome associated with potentially life-threatening toxicity following 5-fluorouracil administration. Clin Colorectal Cancer. 2004;4:181–9. Ezzeldin H, Diasio R. Dihydropyrimidine dehydrogenase deficiency, a pharmacogenetic syndrome associated with potentially life-threatening toxicity following 5-fluorouracil administration. Clin Colorectal Cancer. 2004;4:181–9.
20.
Zurück zum Zitat Lee A, Ezzeldin H, Fourie J, Diasio R. Dihidropyrimidine dehydrogenase deficiency: impact of pharmacogenetics on 5-fluorouracil therapy. Clin Adv Hematol Oncol. 2004;2:527–32. Lee A, Ezzeldin H, Fourie J, Diasio R. Dihidropyrimidine dehydrogenase deficiency: impact of pharmacogenetics on 5-fluorouracil therapy. Clin Adv Hematol Oncol. 2004;2:527–32.
21.
Zurück zum Zitat Etienne-Grimaldi MC, Boyer JC, Thomas F, et al. UGT1A1 genotype and irinotecan therapy: general review and implementation in routine practice. Fundam Clin Pharmacol. 2015;29:219–37. Etienne-Grimaldi MC, Boyer JC, Thomas F, et al. UGT1A1 genotype and irinotecan therapy: general review and implementation in routine practice. Fundam Clin Pharmacol. 2015;29:219–37.
22.
Zurück zum Zitat Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–25. Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–25.
23.
Zurück zum Zitat Baldini C, Escande A, Bouché, et al. Safety and efficacy of FOLFIRINOX in elderly patients with metastatic or locally advanced pancreatic adenocarcinoma: a retrospective analysis. Pancreatology. 2017;17:146–9. Baldini C, Escande A, Bouché, et al. Safety and efficacy of FOLFIRINOX in elderly patients with metastatic or locally advanced pancreatic adenocarcinoma: a retrospective analysis. Pancreatology. 2017;17:146–9.
24.
Zurück zum Zitat Guion-Dusserre JF, Bertaut A, Ghiringhelli F, et al. Folfirinox in elderly patients with pancreatic or colorectal cancer-tolerance and efficacy. World J Gastroenterol. 2016;22:9378–86. Guion-Dusserre JF, Bertaut A, Ghiringhelli F, et al. Folfirinox in elderly patients with pancreatic or colorectal cancer-tolerance and efficacy. World J Gastroenterol. 2016;22:9378–86.
25.
Zurück zum Zitat Yamamoto T, Sunakawa Y, Kubota Y, et al. Tolerability and clinical outcomes in elderly patients with advanced pancreatic cancer treated with FOLFIRINOX. J Clin Oncol. 2016;34(suppl 4S; abstr 404). Yamamoto T, Sunakawa Y, Kubota Y, et al. Tolerability and clinical outcomes in elderly patients with advanced pancreatic cancer treated with FOLFIRINOX. J Clin Oncol. 2016;34(suppl 4S; abstr 404).
26.
Zurück zum Zitat Stein SM, James ES, Deng Y, et al. Final analysis of a phase II study of modified FOLFIRINOX in locally advanced or metastatic pancreatic cancer. Br J Cancer. 2016;114:737–43. Stein SM, James ES, Deng Y, et al. Final analysis of a phase II study of modified FOLFIRINOX in locally advanced or metastatic pancreatic cancer. Br J Cancer. 2016;114:737–43.
27.
Zurück zum Zitat Alessandretti MB, Brandao EP, Abrahão CM, et al. Safety and efficacy of modified dose-attenuated FOLFIRINOX chemotherapy in patients over 65 years with advanced pancreatic adenocarcinoma. J Clin Oncol. 2013;31(suppl; abstr e15176). Alessandretti MB, Brandao EP, Abrahão CM, et al. Safety and efficacy of modified dose-attenuated FOLFIRINOX chemotherapy in patients over 65 years with advanced pancreatic adenocarcinoma. J Clin Oncol. 2013;31(suppl; abstr e15176).
28.
Zurück zum Zitat Mulvey A, Dean A, Hayden I. Modified FOLFIRINOX retains efficacy in pancreatic adenocarcinoma: an Australian experience. Ann Oncol. 2014;25(suppl 4):iv210–53. Mulvey A, Dean A, Hayden I. Modified FOLFIRINOX retains efficacy in pancreatic adenocarcinoma: an Australian experience. Ann Oncol. 2014;25(suppl 4):iv210–53.
29.
Zurück zum Zitat Blazer MA, Wu CS, Goldberg RM, et al. Tolerability and efficacy of modified FOLFIRINOX (mFOLFIRINOX) in patients with borderline-resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAURPC). J Clin Oncol. 2014;32(suppl 3, abstr 275). Blazer MA, Wu CS, Goldberg RM, et al. Tolerability and efficacy of modified FOLFIRINOX (mFOLFIRINOX) in patients with borderline-resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAURPC). J Clin Oncol. 2014;32(suppl 3, abstr 275).
30.
Zurück zum Zitat Sanoff HK, Bleiberg H, Goldberg RM. Managing older patients with colorectal cancer. J Clin Oncol. 2007;25:1891–7. Sanoff HK, Bleiberg H, Goldberg RM. Managing older patients with colorectal cancer. J Clin Oncol. 2007;25:1891–7.
31.
Zurück zum Zitat Smith TJ, Bohlke K, Lyman GH. Recommendations for the use of WBC growth factors: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2015;33:3199–212. Smith TJ, Bohlke K, Lyman GH. Recommendations for the use of WBC growth factors: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2015;33:3199–212.
32.
Zurück zum Zitat Clinical Trials.gov. NCT02143219: Phase-2 study evaluating overall response rate (efficacy) and autonomy daily living preservation (tolerance) of “FOLFIRINOX” pharmacogenetic dose adjusted, in elderly patients (70 yo. or older) with a metastatic pancreatic adenocarcinoma. Available at: https://clinicaltrials.gov/ct2/show/NCT02143219. Accessed 15 Feb 2017. Clinical Trials.gov. NCT02143219: Phase-2 study evaluating overall response rate (efficacy) and autonomy daily living preservation (tolerance) of “FOLFIRINOX” pharmacogenetic dose adjusted, in elderly patients (70 yo. or older) with a metastatic pancreatic adenocarcinoma. Available at: https://​clinicaltrials.​gov/​ct2/​show/​NCT02143219. Accessed 15 Feb 2017.
33.
Zurück zum Zitat Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369:1691–703. Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369:1691–703.
34.
Zurück zum Zitat Goldstein D, El-Maraghi RH, Heinemann V, et al. Nab-paclitaxel plus gemcitabine for metastatic pancreatic cancer: long-term survival from a phase III trial. J Natl Cancer Inst. 2015. Goldstein D, El-Maraghi RH, Heinemann V, et al. Nab-paclitaxel plus gemcitabine for metastatic pancreatic cancer: long-term survival from a phase III trial. J Natl Cancer Inst. 2015.
35.
Zurück zum Zitat Giordano G, Vaccaro V, Lucchini E, 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. J Clin Oncol. 2015;33(suppl 3; abstr 424). Giordano G, Vaccaro V, Lucchini E, 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. J Clin Oncol. 2015;33(suppl 3; abstr 424).
36.
Zurück zum Zitat Vogl U, Vormittag L, Winkler T, et al. Gemcitabine plus nab-paclitaxel in metastatic or locally inoperable pancreatic cancer – a single center experience. Ann Oncol. 2015;26(suppl 4):iv52. Vogl U, Vormittag L, Winkler T, et al. Gemcitabine plus nab-paclitaxel in metastatic or locally inoperable pancreatic cancer – a single center experience. Ann Oncol. 2015;26(suppl 4):iv52.
37.
Zurück zum Zitat De Vita F, Ventriglia J, Febbraro A, et al. NAB-paclitaxel and gemcitabine in metastatic pancreatic ductal adenocarcinoma (PDAC): from clinical trials to clinical practice. BMC Cancer. 2016;16:709. De Vita F, Ventriglia J, Febbraro A, et al. NAB-paclitaxel and gemcitabine in metastatic pancreatic ductal adenocarcinoma (PDAC): from clinical trials to clinical practice. BMC Cancer. 2016;16:709.
38.
Zurück zum Zitat Scheithauer W, Ramanathan RK, Moore M, et al. Dose modification and efficacy of nab-paclitaxel plus gemcitabine vs. gemcitabine for patients with metastatic pancreatic cancer: phase III MPACT trial. J Gastrointest Oncol. 2016;7:469–78. Scheithauer W, Ramanathan RK, Moore M, et al. Dose modification and efficacy of nab-paclitaxel plus gemcitabine vs. gemcitabine for patients with metastatic pancreatic cancer: phase III MPACT trial. J Gastrointest Oncol. 2016;7:469–78.
39.
Zurück zum Zitat Ahn DH, Krishna K, Blazer M, et al. A modified regimen of biweekly gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer is both tolerable and effective: a retrospective analysis. Ther Adv Med Oncol. 2017. Ahn DH, Krishna K, Blazer M, et al. A modified regimen of biweekly gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer is both tolerable and effective: a retrospective analysis. Ther Adv Med Oncol. 2017.
40.
Zurück zum Zitat Krishna K, Blazer MA, Wei L, et al. Modified gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer (MPC): a single-institution experience. J Clin Oncol. 2015;33(suppl 3; abstr 366). Krishna K, Blazer MA, Wei L, et al. Modified gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer (MPC): a single-institution experience. J Clin Oncol. 2015;33(suppl 3; abstr 366).
41.
Zurück zum Zitat Osman MAM, McDermott R, Fennelly D. A modified regimen of nab-paclitaxel and gemcitabine in advanced pancreatic cancer. Ann Oncol. 2016;27(suppl 6):666P. Osman MAM, McDermott R, Fennelly D. A modified regimen of nab-paclitaxel and gemcitabine in advanced pancreatic cancer. Ann Oncol. 2016;27(suppl 6):666P.
44.
Zurück zum Zitat Wang-Gillam A, Li CP, Bodoky G, et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomized, open-label, phase 3 trial. Lancet. 2016;387:545–57. Wang-Gillam A, Li CP, Bodoky G, et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomized, open-label, phase 3 trial. Lancet. 2016;387:545–57.
45.
Zurück zum Zitat Clinical Trials.gov. NCT02551991: A randomized, open-label phase 2 study of nanoliposomal irinotecan (nal-IRI)-containing regimens versus nab-paclitaxel plus gemcitabine in patients with previously untreated, metastatic pancreatic adenocarcinoma. Available at: https://clinicaltrials.gov/ct2/show/NCT02551991. Accessed 2017. Clinical Trials.gov. NCT02551991: A randomized, open-label phase 2 study of nanoliposomal irinotecan (nal-IRI)-containing regimens versus nab-paclitaxel plus gemcitabine in patients with previously untreated, metastatic pancreatic adenocarcinoma. Available at: https://​clinicaltrials.​gov/​ct2/​show/​NCT02551991. Accessed 2017.
46.
Zurück zum Zitat Hubner RA, Worsnop F, Cunningham D, Chau I. Gemcitabine plus capecitabine in unselected patients with advanced pancreatic cancer. Pancreas. 2013;42:511–5.CrossRefPubMed Hubner RA, Worsnop F, Cunningham D, Chau I. Gemcitabine plus capecitabine in unselected patients with advanced pancreatic cancer. Pancreas. 2013;42:511–5.CrossRefPubMed
47.
Zurück zum Zitat Neoptolemos JP, Stocken DD, Freiss H, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. New Engl J Med. 2004;350:1200–10.CrossRefPubMed Neoptolemos JP, Stocken DD, Freiss H, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. New Engl J Med. 2004;350:1200–10.CrossRefPubMed
48.
Zurück zum Zitat Ben-Josef E, Guthrie KA, El-Khoueiry AB, et al. SWOG S0809: a phase II intergroup trial of adjuvant capecitabine and gemcitabine followed by radiotherapy and concurrent capecitabine in extraheatic cholangiocarcinoma and gallbladder carcinoma. J Clin Oncol. 2015;33:2617–22. Ben-Josef E, Guthrie KA, El-Khoueiry AB, et al. SWOG S0809: a phase II intergroup trial of adjuvant capecitabine and gemcitabine followed by radiotherapy and concurrent capecitabine in extraheatic cholangiocarcinoma and gallbladder carcinoma. J Clin Oncol. 2015;33:2617–22.
49.
Zurück zum Zitat Li D, Capanu M, Yu KH, Lowery MA, Kelsen DP, O’Reilly EM. Treatment, outcomes, and clinical trial participation in elderly patients with metastatic pancreas adenocarcinoma. Clin Colorectal Cancer. 2015;14:269–76. Li D, Capanu M, Yu KH, Lowery MA, Kelsen DP, O’Reilly EM. Treatment, outcomes, and clinical trial participation in elderly patients with metastatic pancreas adenocarcinoma. Clin Colorectal Cancer. 2015;14:269–76.
Metadaten
Titel
Systemic Combination Chemotherapy in Elderly Pancreatic Cancer: a Review
verfasst von
Gwenalyn Garcia
Marcel Odaimi
Publikationsdatum
16.03.2017
Verlag
Springer US
Erschienen in
Journal of Gastrointestinal Cancer / Ausgabe 2/2017
Print ISSN: 1941-6628
Elektronische ISSN: 1941-6636
DOI
https://doi.org/10.1007/s12029-017-9930-0

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