Skip to main content
Top
Published in: Annals of Surgical Oncology 7/2018

01-07-2018 | Pancreatic Tumors

FOLFIRINOX Versus Gemcitabine/Nab-Paclitaxel for Neoadjuvant Treatment of Resectable and Borderline Resectable Pancreatic Head Adenocarcinoma

Authors: Mashaal Dhir, MD, Mazen S. Zenati, MD, PhD, Ahmad Hamad, MD, Aatur D. Singhi, MD, Nathan Bahary, MD, Melissa E. Hogg, MD, Herbert J. Zeh III, MD, Amer H. Zureikat, MD, FACS

Published in: Annals of Surgical Oncology | Issue 7/2018

Login to get access

Abstract

Background

Both FOLFIRINOX and gemcitabine/nab-paclitaxel (G-nP) are used increasingly in the neoadjuvant treatment (NAT) of pancreatic ductal adenocarcinoma (PDA). This study aimed to compare neoadjuvant FOLFIRINOX and G-nP in the treatment of resectable (R) and borderline resectable (BR) head PDA.

Methods

A single-institution retrospective review of R and BR patients undergoing pancreaticoduodenectomy after NAT with FOLFIRINOX or G-nP was performed. Comparative analysis was performed using inverse-probability-weighted (IPW) estimators. The end points of the study were overall survival (OS) and an 80% reduction in CA19-9 with NAT.

Results

In this study, 193 patients were analyzed, with 73 patients receiving FOLFIRINOX and 120 patients receiving G-nP. The median OS was 38.7 months for FOLFIRINOX versus 28.6 months for G-nP (p = 0.214). The patients who received FOLFIRINOX were younger and had fewer comorbidities, more BR disease, and larger tumors than those treated with G-nP (all p < 0.05). The two regimens were equally effective in achieving an 80% decline in CA19-9 (p = 0.8). The R0 resection rates were similar (80%), but FOLFIRINOX was associated with a reduction in pN1 disease (56% vs. 72%; p = 0.028). The receipt of adjuvant therapy was similar (74 vs. 75%; p = 0.79). In the Cox regression analysis with adjustment for baseline and treatment-related variables (FOLFIRINOX vs. G-nP, age, gender, computed tomography (CT) tumor size, BR vs. R, pre-NAT CA19-9), regimen type was not associated with a survival benefit. In the IPW analysis of 166 patients, however, the average treatment effect of FOLFIRINOX was to increase OS by 4.9 months compared with G-nP (p = 0.012).

Conclusions

Both FOLFIRINOX and G-nP are viable options for neoadjuvant treatment of PDA. In this study, neoadjuvant FOLFIRINOX was associated with a 4.9-month improvement in survival compared with G-nP after adjustment for covariates.
Appendix
Available only for authorised users
Literature
3.
go back to reference Corsini MM, Miller RC, Haddock MG, et al. Adjuvant radiotherapy and chemotherapy for pancreatic carcinoma: the Mayo Clinic experience (1975–2005). J Clin Oncol. 2008;26:3511–6.CrossRefPubMed Corsini MM, Miller RC, Haddock MG, et al. Adjuvant radiotherapy and chemotherapy for pancreatic carcinoma: the Mayo Clinic experience (1975–2005). J Clin Oncol. 2008;26:3511–6.CrossRefPubMed
4.
go back to reference Herman JM, Swartz MJ, Hsu CC, et al. Analysis of fluorouracil-based adjuvant chemotherapy and radiation after pancreaticoduodenectomy for ductal adenocarcinoma of the pancreas: results of a large, prospectively collected database at the Johns Hopkins Hospital. J Clin Oncol. 2008;26:3503–10.CrossRefPubMed Herman JM, Swartz MJ, Hsu CC, et al. Analysis of fluorouracil-based adjuvant chemotherapy and radiation after pancreaticoduodenectomy for ductal adenocarcinoma of the pancreas: results of a large, prospectively collected database at the Johns Hopkins Hospital. J Clin Oncol. 2008;26:3503–10.CrossRefPubMed
5.
go back to reference Parmar AD, Vargas GM, Tamirisa NP, Sheffield KM, Riall TS. Trajectory of care and use of multimodality therapy in older patients with pancreatic adenocarcinoma. Surgery. 2014;156:280–9.CrossRefPubMed Parmar AD, Vargas GM, Tamirisa NP, Sheffield KM, Riall TS. Trajectory of care and use of multimodality therapy in older patients with pancreatic adenocarcinoma. Surgery. 2014;156:280–9.CrossRefPubMed
6.
go back to reference Evans DB, Varadhachary GR, Crane CH, et al. Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26:3496–502.CrossRefPubMed Evans DB, Varadhachary GR, Crane CH, et al. Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26:3496–502.CrossRefPubMed
7.
go back to reference Katz MH, Pisters PW, Evans DB, et al. Borderline resectable pancreatic cancer: the importance of this emerging stage of disease. J Am Coll Surg. 2008;206:833–46.CrossRefPubMedPubMedCentral Katz MH, Pisters PW, Evans DB, et al. Borderline resectable pancreatic cancer: the importance of this emerging stage of disease. J Am Coll Surg. 2008;206:833–46.CrossRefPubMedPubMedCentral
8.
go back to reference Varadhachary GR, Wolff RA, Crane CH, et al. Preoperative gemcitabine and cisplatin followed by gemcitabine-based chemoradiation for resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26:3487–95.CrossRefPubMed Varadhachary GR, Wolff RA, Crane CH, et al. Preoperative gemcitabine and cisplatin followed by gemcitabine-based chemoradiation for resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26:3487–95.CrossRefPubMed
9.
go back to reference Andriulli A, Festa V, Botteri E, et al. Neoadjuvant/preoperative gemcitabine for patients with localized pancreatic cancer: a meta-analysis of prospective studies. Ann Surg Oncol. 2012;19:1644–62.CrossRefPubMed Andriulli A, Festa V, Botteri E, et al. Neoadjuvant/preoperative gemcitabine for patients with localized pancreatic cancer: a meta-analysis of prospective studies. Ann Surg Oncol. 2012;19:1644–62.CrossRefPubMed
10.
go back to reference Assifi MM, Lu X, Eibl G, Reber HA, Li G, Hines OJ. Neoadjuvant therapy in pancreatic adenocarcinoma: a meta-analysis of phase II trials. Surgery. 2011;150:466–73.CrossRefPubMed Assifi MM, Lu X, Eibl G, Reber HA, Li G, Hines OJ. Neoadjuvant therapy in pancreatic adenocarcinoma: a meta-analysis of phase II trials. Surgery. 2011;150:466–73.CrossRefPubMed
11.
go back to reference Gillen S, Schuster T, Meyer Zum Buschenfelde C, Friess H, Kleeff J. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med. 2010;7:e1000267.CrossRefPubMedPubMedCentral Gillen S, Schuster T, Meyer Zum Buschenfelde C, Friess H, Kleeff J. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med. 2010;7:e1000267.CrossRefPubMedPubMedCentral
12.
go back to reference Burris HA III, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997;15:2403–13.CrossRefPubMed Burris HA III, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997;15:2403–13.CrossRefPubMed
13.
go back to reference Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–25.CrossRefPubMed Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–25.CrossRefPubMed
14.
go back to reference 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.CrossRef 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.CrossRef
15.
go back to reference Tempero MA, Malafa MP, Al-Hawary M, et al. Pancreatic adenocarcinoma, version 2.2017, NCCN Clinical Practice Guidelines in Oncology. JNCCN J Natl Comp Cancer Network. 2017;15:1028–61.CrossRef Tempero MA, Malafa MP, Al-Hawary M, et al. Pancreatic adenocarcinoma, version 2.2017, NCCN Clinical Practice Guidelines in Oncology. JNCCN J Natl Comp Cancer Network. 2017;15:1028–61.CrossRef
16.
18.
go back to reference de Geus SW, Evans DB, Bliss LA, et al. Neoadjuvant therapy versus upfront surgical strategies in resectable pancreatic cancer: a Markov decision analysis. Eur J Surg Oncol. 2016;42:1552–60.CrossRefPubMed de Geus SW, Evans DB, Bliss LA, et al. Neoadjuvant therapy versus upfront surgical strategies in resectable pancreatic cancer: a Markov decision analysis. Eur J Surg Oncol. 2016;42:1552–60.CrossRefPubMed
19.
go back to reference Mokdad AA, Minter RM, Zhu H, et al. Neoadjuvant therapy followed by resection versus upfront resection for resectable pancreatic cancer: a propensity score-matched analysis. J Clin Oncol. 2017;35:515–22.CrossRefPubMed Mokdad AA, Minter RM, Zhu H, et al. Neoadjuvant therapy followed by resection versus upfront resection for resectable pancreatic cancer: a propensity score-matched analysis. J Clin Oncol. 2017;35:515–22.CrossRefPubMed
20.
go back to reference Dhir M, Malhotra GK, Sohal DPS, et al. Neoadjuvant treatment of pancreatic adenocarcinoma: a systematic review and meta-analysis of 5520 patients. World J Surg Oncol. 2017;15:183.CrossRefPubMedPubMedCentral Dhir M, Malhotra GK, Sohal DPS, et al. Neoadjuvant treatment of pancreatic adenocarcinoma: a systematic review and meta-analysis of 5520 patients. World J Surg Oncol. 2017;15:183.CrossRefPubMedPubMedCentral
21.
go back to reference Epelboym I, Zenati MS, Hamad A, et al. Analysis of perioperative chemotherapy in resected pancreatic cancer: identifying the number and sequence of chemotherapy cycles needed to optimize survival. Ann Surg Oncol. 2017;24:2744–51.CrossRefPubMed Epelboym I, Zenati MS, Hamad A, et al. Analysis of perioperative chemotherapy in resected pancreatic cancer: identifying the number and sequence of chemotherapy cycles needed to optimize survival. Ann Surg Oncol. 2017;24:2744–51.CrossRefPubMed
22.
go back to reference Sohal D, McDonough SL, Ahmad SA, et al. SWOG S1505: a randomized phase II study of perioperative mFOLFIRINOX vs gemcitabine/nab-paclitaxel as therapy for resectable pancreatic adenocarcinom. J Clin Oncol. 2017;35(4 Suppl):TPS508–TPS508.CrossRef Sohal D, McDonough SL, Ahmad SA, et al. SWOG S1505: a randomized phase II study of perioperative mFOLFIRINOX vs gemcitabine/nab-paclitaxel as therapy for resectable pancreatic adenocarcinom. J Clin Oncol. 2017;35(4 Suppl):TPS508–TPS508.CrossRef
23.
go back to reference Katz MH, Fleming JB, Bhosale P, et al. Response of borderline resectable pancreatic cancer to neoadjuvant therapy is not reflected by radiographic indicators. Cancer. 2012;118:5749–56.CrossRefPubMed Katz MH, Fleming JB, Bhosale P, et al. Response of borderline resectable pancreatic cancer to neoadjuvant therapy is not reflected by radiographic indicators. Cancer. 2012;118:5749–56.CrossRefPubMed
24.
go back to reference Ferrone CR, Marchegiani G, Hong TS, et al. Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg. 2015;261:12–7.CrossRefPubMed Ferrone CR, Marchegiani G, Hong TS, et al. Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg. 2015;261:12–7.CrossRefPubMed
25.
go back to reference Boone BA, Steve J, Zenati MS, et al. Serum CA19-9 response to neoadjuvant therapy is associated with outcome in pancreatic adenocarcinoma. Ann Surg Oncol. 2014;21:4351–8.CrossRefPubMed Boone BA, Steve J, Zenati MS, et al. Serum CA19-9 response to neoadjuvant therapy is associated with outcome in pancreatic adenocarcinoma. Ann Surg Oncol. 2014;21:4351–8.CrossRefPubMed
Metadata
Title
FOLFIRINOX Versus Gemcitabine/Nab-Paclitaxel for Neoadjuvant Treatment of Resectable and Borderline Resectable Pancreatic Head Adenocarcinoma
Authors
Mashaal Dhir, MD
Mazen S. Zenati, MD, PhD
Ahmad Hamad, MD
Aatur D. Singhi, MD
Nathan Bahary, MD
Melissa E. Hogg, MD
Herbert J. Zeh III, MD
Amer H. Zureikat, MD, FACS
Publication date
01-07-2018
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 7/2018
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-018-6512-8

Other articles of this Issue 7/2018

Annals of Surgical Oncology 7/2018 Go to the issue