Skip to main content

Advertisement

Log in

Systemic Combination Chemotherapy in Elderly Pancreatic Cancer: a Review

  • Review Article
  • Published:
Journal of Gastrointestinal Cancer Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Howlader N, Noone AM, Krapcho M, et al. (eds). SEER Cancer Statistics Review, 1975-2013, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2013/, based on November 2015 SEER data submission, posted to the SEER web site, April 2016.

  2. 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. 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. 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. 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. Nagrial AM, Chang DK, Nguyen NQ, et al. Adjuvant chemotherapy in elderly patients with pancreatic cancer. Br J Cancer. 2014;110:313–9.

  7. 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. 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. 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. 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. 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. 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. Lichtman SM, Boparai MK. Anticancer drug therapy in the older cancer patient: pharmacology and polypharmacy. Curr Treat Options Oncol. 2008;9:191–203.

  14. XELODA® (capecitabine). Available at: https://www.gene.com/download/pdf/xeloda_prescribing.pdf. Accessed 15 Feb 2017.

  15. CAMPTOSAR® (irinotecan). Available at: http://labeling.pfizer.com/showlabeling.aspx?id=533. Accessed 13 Feb 2017.

  16. ONIVYDE™ (irinotecan liposome injection). Available at: https://www.onivyde.com/_assets/pdf/ONIVYDE_USPI.pdf. Accessed 15 Feb 2017.

  17. ABRAXANE® (nab-paclitaxel). Available at: http://www.celgene.com/content/uploads/abraxane-pi.pdf. Accessed 29 Jan 2017.

  18. 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. 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. 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. 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. Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–25.

  23. 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. 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. 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. 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. 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. 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. 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. Sanoff HK, Bleiberg H, Goldberg RM. Managing older patients with colorectal cancer. J Clin Oncol. 2007;25:1891–7.

  31. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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.

  42. Clinical Trials.gov. NCT02391662: a phase II study of nab-paclitaxel and gemcitabine, in elderly patients with previously untreated, metastatic pancreatic adenocarcinoma. Available at: https://clinicaltrials.gov/ct2/show/NCT02391662. Accessed 15 Feb 2017.

  43. Clinical Trials.gov. NCT02812992: a multicenter phase 4 geriatric assessment directed trial to evaluate gemcitabine +/- nab-paclitaxel in elderly pancreatic cancer patients. Available at: https://clinicaltrials.gov/ct2/show/NCT02812992. Accessed 15 Feb 2017.

  44. 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. 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. Hubner RA, Worsnop F, Cunningham D, Chau I. Gemcitabine plus capecitabine in unselected patients with advanced pancreatic cancer. Pancreas. 2013;42:511–5.

    Article  CAS  PubMed  Google Scholar 

  47. 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.

    Article  CAS  PubMed  Google Scholar 

  48. 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. 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.

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gwenalyn Garcia.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Garcia, G., Odaimi, M. Systemic Combination Chemotherapy in Elderly Pancreatic Cancer: a Review. J Gastrointest Canc 48, 121–128 (2017). https://doi.org/10.1007/s12029-017-9930-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12029-017-9930-0

Keywords

Navigation