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Medical Oncology

, 36:87 | Cite as

Comparison of conventional versus liposomal irinotecan in combination with fluorouracil for advanced pancreatic cancer: a single-institution experience

  • Justin C. Tossey
  • Joshua Reardon
  • Jeffrey B. VanDeusen
  • Anne M. Noonan
  • Kyle Porter
  • Matthew J. ArangoEmail author
Original Paper

Abstract

The majority of pancreatic cancers are diagnosed at an advanced stage, when surgical options are limited and treatment relies on systemic chemotherapy. In the NAPOLI-1 trial, liposomal irinotecan in combination with fluorouracil (nal-iri/5FU) was shown to improve overall survival when compared to fluorouracil alone for metastatic pancreatic cancer. Other retrospective studies have shown the combination of fluorouracil and conventional irinotecan (FOLFIRI) to be a viable option, though no randomized trials have compared nal-iri/5FU to FOLFIRI. The purpose of this single-center, retrospective, cohort study was to determine if nal-iri/5FU and FOLFIRI are similarly effective for the treatment of advanced pancreatic cancer. Due to the potential for treatment bias, inverse probability of treatment weighting was utilized to correct for baseline differences between the groups. The primary outcome of progression-free survival was similar at 4.1 months for nal-iri/5FU and 3.1 months for FOLFIRI. Overall survival and adverse effect frequency were also similar. Pegfilgrastim was used in 16% and 15% of patients, respectively, and nal-iri/5FU patients required significantly less atropine during treatment (36 vs. 70%). A cost analysis was conducted and concluded that the treatment with nal-iri/5FU was nearly 30 times more expensive than FOLFIRI treatment. Together, these data suggest a potential role for FOLFIRI for the treatment of advanced pancreatic cancer in the absence of clear benefits in effectiveness, toxicity, or cost for nal-iri/5FU.

Keywords

Metastatic pancreatic adenocarcinoma Nanoliposomal irinotecan FOLFIRI Cost-effective 

Notes

Compliance with ethical standards

Conflict of interest

Anne Noonan served as a paid member of the Data Safety Monitoring Board for Helsinn in 2015–2016 and a paid advisory board member for QED Therapeutics and Exelixis in 2019. No other authors have any potential conflicts to declare.

References

  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7–30.CrossRefGoogle Scholar
  2. 2.
    Ryan DP, Hong TS, Bardeesy N. Pancreatic adenocarcinoma. N Engl J Med. 2014;371(22):2140–1.PubMedGoogle Scholar
  3. 3.
    Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817–25.CrossRefPubMedGoogle Scholar
  4. 4.
    Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691–703.CrossRefGoogle Scholar
  5. 5.
    Onivyde (irinotecan liposome) [package insert]. Basking Ridge: Ipsen Biopharmaceuticals, Inc.; 2017.Google Scholar
  6. 6.
    Wang-Gillam A, Li CP, Bodoky G, Dean A, Shan YS, Jameson G, et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet. 2016;387(10018):545–57.CrossRefPubMedGoogle Scholar
  7. 7.
    Gill S, Ko YJ, Cripps C, Beaudoin A, Dhesy-Thind S, Zulfiqar M, et al. PANCREOX: a randomized phase III study of fluorouracil/leucovorin with or without oxaliplatin for second-line advanced pancreatic cancer in patients who have received gemcitabine-based chemotherapy. J Clin Oncol. 2016;34(32):3914–20.CrossRefPubMedGoogle Scholar
  8. 8.
    Oettle H, Riess H, Stieler JM, Heil G, Schwaner I, Seraphin J, et al. Second-line oxaliplatin, folinic acid, and fluorouracil versus folinic acid and fluorouracil alone for gemcitabine-refractory pancreatic cancer: outcomes from the CONKO-003 trial. J Clin Oncol. 2014;32(23):2423–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Gebbia V, Maiello E, Giuliani F, Borsellino N, Arcara C, Colucci G. Irinotecan plus bolus/infusional 5-Fluorouracil and leucovorin in patients with pretreated advanced pancreatic carcinoma: a multicenter experience of the Gruppo Oncologico Italia Meridionale. Am J Clin Oncol. 2010;33(5):461–4.CrossRefPubMedGoogle Scholar
  10. 10.
    Neuzillet C, Hentic O, Rousseau B, Rebours V, Bengrine-Lefevre L, Bonnetain F, et al. FOLFIRI regimen in metastatic pancreatic adenocarcinoma resistant to gemcitabine and platinum-salts. World J Gastroenterol. 2012;18(33):4533–41.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Yoo C, Hwang JY, Kim JE, Kim TW, Lee JS, Park DH, et al. A randomised phase II study of modified FOLFIRI.3 vs modified FOLFOX as second-line therapy in patients with gemcitabine-refractory advanced pancreatic cancer. Br J Cancer. 2009;101(10):1658–63.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Zaniboni A, Aitini E, Barni S, Ferrari D, Cascinu S, Catalano V, et al. FOLFIRI as second-line chemotherapy for advanced pancreatic cancer: a GISCAD multicenter phase II study. Cancer Chemother Pharmacol. 2012;69(6):1641–5.CrossRefPubMedGoogle Scholar
  13. 13.
    Kalra AV, Kim J, Klinz SG, Paz N, Cain J, Drummond DC, et al. Preclinical activity of nanoliposomal irinotecan is governed by tumor deposition and intratumor prodrug conversion. Cancer Res. 2014;74(23):7003–13.CrossRefPubMedGoogle Scholar
  14. 14.
    Goldstein DA, Krishna K, Flowers CR, El-Rayes BF, Bekaii-Saab T, Noonan AM. Cost description of chemotherapy regimens for the treatment of metastatic pancreas cancer. Med Oncol. 2016;33(5):48.CrossRefPubMedGoogle Scholar
  15. 15.
    ASP drug pricing files. Centers for Medicare and Medicaid Services. https://www.cms.gov/Medicare/Medicare-Fee-for-Service-Part-B-Drugs/McrPartBDrugAvgSalesPrice/2019ASPFiles.html. Accessed 10 Apr 2019.
  16. 16.
    Fryar CD, Kruszon-Moran D, Gu Q, Ogden CL. Mean body weight, height, waist circumference, and body mass index among adults: United States, 1999–2000 through 2015–2016. Natl Health Stat Rep. 2018;122:1–16.Google Scholar
  17. 17.
    Tumeh JW, Moore SG, Shapiro R, Flowers CR. Practical approach for using Medicare data to estimate costs for cost-effectiveness analysis. Expert Rev Pharmacoecon Outcomes Res. 2005;5(2):153–62.CrossRefPubMedGoogle Scholar
  18. 18.
    Wang-Gillam A, Hubner RA, Siveke JT, Von Hoff DD, Belanger B, de Jong FA, et al. NAPOLI-1 phase 3 study of liposomal irinotecan in metastatic pancreatic cancer: final overall survival analysis and characteristics of long-term survivors. Eur J Cancer. 2019;108:78–87.CrossRefPubMedGoogle Scholar
  19. 19.
    Glassman DC, Palmaira RL, Covington CM, Desai AM, Ku GY, Li J, et al. Nanoliposomal irinotecan with fluorouracil for the treatment of advanced pancreatic cancer, a single institution experience. BMC Cancer. 2018;18(1):693.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Ahn DH, Krishna K, Blazer M, Reardon J, Wei L, Wu C, 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;9(2):75–82.CrossRefPubMedGoogle Scholar
  21. 21.
    Fleeman N, Abdulla A, Bagust A, Beale S, Richardson M, Stainthorpe A, et al. Pegylated liposomal irinotecan hydrochloride trihydrate for treating pancreatic cancer after gemcitabine: an evidence review group perspective of a NICE single technology appraisal. Pharmacoeconomics. 2018;36(3):289–99.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of PharmacyThe Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research InstituteColumbusUSA
  2. 2.Division of Medical Oncology, Department of Internal MedicineThe Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research InstituteColumbusUSA
  3. 3.Department of Biomedical Informatics, Center for BiostatisticsThe Ohio State UniversityColumbusUSA

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