Systematic Review of Resection Rates and Clinical Outcomes After FOLFIRINOX-Based Treatment in Patients with Locally Advanced Pancreatic Cancer

Steffi J Rombouts, Marieke S Walma, Jantien A Vogel, Lennart B van Rijssen, Johanna W Wilmink, Nadia Haj Mohammad, Hjalmar C van Santvoort, I Quintus Molenaar, Marc G Besselink, Steffi J Rombouts, Marieke S Walma, Jantien A Vogel, Lennart B van Rijssen, Johanna W Wilmink, Nadia Haj Mohammad, Hjalmar C van Santvoort, I Quintus Molenaar, Marc G Besselink

Abstract

Background: FOLFIRINOX prolongs survival in patients with metastatic pancreatic cancer and may also benefit patients with locally advanced pancreatic cancer (LAPC). Furthermore, it may downstage a proportion of LAPC into (borderline) resectable disease, however data are lacking. This review assessed outcomes after FOLFIRINOX-based therapy in LAPC.

Methods: The PubMed, EMBASE and Cochrane library databases were systematically searched for studies published to 31 August 2015. Primary outcome was the (R0) resection rate.

Results: Fourteen studies involving 365 patients with LAPC were included; three studies administered a modified FOLFIRINOX regimen. Of all patients, 57 % (n = 208) received radiotherapy. The pooled resection rate was 28 % (n = 103, 77 % R0), with a perioperative mortality of 3 % (n = 2), and median overall survival ranged from 8.9 to 25.0 months. Survival data after resection were scarce, with only one study reporting a median overall survival of 24.9 months in 28 patients. A complete pathologic response was found in 6 of 85 (7 %) resected specimens. Dose reductions were described in up to 65 % of patients, grade 3-4 toxicity occurred in 23 % (n = 51) of patients, and 2 % (n = 5) had to discontinue treatment. Data of patients treated solely with FOLFIRINOX, without additional radiotherapy, were available from 292 patients: resection rate was 12 % (n = 29, 70 % R0), with 15.7 months median overall survival and 19 % (n = 34) grade 3-4 toxicity.

Conclusions: Outcomes after FOLFIRINOX-based therapy in patients with LAPC seem very promising but further prospective studies are needed, especially with regard to survival after resection.

Figures

Fig. 1
Fig. 1
Study selection process

References

    1. Vincent A, Herman J, Schulick R, Hruban RH, Goggins M. Pancreatic cancer. Lancet. 2011;378(9791):607–620. doi: 10.1016/S0140-6736(10)62307-0.
    1. Burris HA, 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, 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(6):2403–2413.
    1. 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):1817–1825. doi: 10.1056/NEJMoa1011923.
    1. National Comprehensive Cancer Network. NCCN guidelines version 2.2015. Pancreatic adenocarcinoma. 2015. . Accessed 15 Sep 2015.
    1. Moher D, Liberati A, Tetzlaff J, Altman DG. PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg. 2010;8(5):336–341. doi: 10.1016/j.ijsu.2010.02.007.
    1. Oxford Centre for Evidence-Based Medicine, Levels of Evidence Working Group. The 2011 OCEBM levels of evidence. 2014. . Accessed 14 Sep 2015.
    1. Critical Appraisal Skills Programme. 12 questions to help you make sense of cohort study. Cohort Study Checklist 2013. 2011. . Accessed 14 Sep 2015.
    1. Blazer M, Wu C, Goldberg RM, Phillips G, Schmidt C, Muscarella P, et al. Neoadjuvant modified (m) FOLFIRINOX for locally advanced unresectable (LAPC) and borderline resectable (BRPC) adenocarcinoma of the pancreas. Ann Surg Oncol. 2015;22(4):1153–1159. doi: 10.1245/s10434-014-4225-1.
    1. Boone BA, Steve J, Krasinskas AM, Zureikat AH, Lembersky BC, Gibson MK, et al. Outcomes with FOLFIRINOX for borderline resectable and locally unresectable pancreatic cancer. J Surg Oncol. 2013;108(4):236–241. doi: 10.1002/jso.23392.
    1. Conroy T, Paillot B, Francois E, Bugat R, Jacob JH, Stein U, et al. Irinotecan plus oxaliplatin and leucovorin-modulated fluorouracil in advanced pancreatic cancer. A Groupe Tumeurs Digestives of the Federation Nationale des Centres de Lutte Contre le Cancer study. J Clin Oncol. 2005;23(6):1228–1236. doi: 10.1200/JCO.2005.06.050.
    1. Faris JE, Blaszkowsky LS, McDermott S, Guimaraes AR, Szymonifka J, Huynh MA, et al. FOLFIRINOX in locally advanced pancreatic cancer: the Massachusetts General Hospital Cancer Center experience. Oncologist. 2013;18(5):543–548. doi: 10.1634/theoncologist.2012-0435.
    1. Gunturu KS, Yao X, Cong X, Thumar JR, Hochster HS, Stein SM, et al. FOLFIRINOX for locally advanced and metastatic pancreatic cancer: single institution retrospective review of efficacy and toxicity. Med Oncol. 2013;30(1):361. doi: 10.1007/s12032-012-0361-2.
    1. Hohla F, Hopfinger G, Romeder F, Rinnerthaler G, Bezan A, Stattner S, et al. Female gender may predict response to FOLFIRINOX in patients with unresectable pancreatic cancer: a single institution retrospective review. Int J Oncol. 2014;44(1):319–326.
    1. Hosein PJ, Macintyre J, Kawamura C, Maldonado JC, Ernani V, Loaiza-Bonilla A, et al. A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma. BMC Cancer. 2012;12:199. doi: 10.1186/1471-2407-12-199.
    1. Kraemer PC, Schmidt HH, Ladekarl M. Danish experiences with FOLFIRINOX as first-line therapy in patients with inoperable pancreatic cancer. Dan Med J. 2014;61(4):A4819.
    1. Mahaseth H, Brutcher E, Kauh J, Hawk N, Kim S, Chen Z, et al. Modified FOLFIRINOX regimen with improved safety and maintained efficacy in pancreatic adenocarcinoma. Pancreas. 2013;42(8):1311–1315. doi: 10.1097/MPA.0b013e31829e2006.
    1. Marthey L, Sa-Cunha A, Blanc JF, Gauthier M, Cueff A, Francois E, et al. FOLFIRINOX for locally advanced pancreatic adenocarcinoma: results of an AGEO multicenter prospective observational cohort. Ann Surg Oncol. 2015;22(1):295–301. doi: 10.1245/s10434-014-3898-9.
    1. Mellon EA, Hoffe SE, Springett GM, Frakes JM, Strom TJ, Hodul PJ, et al. Long-term outcomes of induction chemotherapy and neoadjuvant stereotactic body radiotherapy for borderline resectable and locally advanced pancreatic adenocarcinoma. Acta Oncol. 2015;54(7):979–985. doi: 10.3109/0284186X.2015.1004367.
    1. Moorcraft SY, Khan K, Peckitt C, Watkins D, Rao S, Cunningham D, et al. FOLFIRINOX for locally advanced or metastatic pancreatic ductal adenocarcinoma: the Royal Marsden experience. Clin Colorectal Cancer. 2014;13(4):232–238. doi: 10.1016/j.clcc.2014.09.005.
    1. Peddi PF, Lubner S, McWilliams R, Tan BR, Picus J, Sorscher SM, et al. Multi-institutional experience with FOLFIRINOX in pancreatic adenocarcinoma. JOP. 2012;13(5):497–501.
    1. Sadot E, Doussot A, O’Reilly EM, Lowery MA, Goodman KA, Do RK, et al. FOLFIRINOX induction therapy for stage 3 pancreatic adenocarcinoma. Ann Surg Oncol. 2015;22(11):3512–3521. doi: 10.1245/s10434-015-4647-4.
    1. Callery MP, Chang KJ, Fishman EK, Talamonti MS. William Traverso L, Linehan DC. Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement. Ann Surg Oncol. 2009;16(7):1727–1733. doi: 10.1245/s10434-009-0408-6.
    1. Petrelli F, Coinu A, Borgonovo K, Cabiddu M, Ghilardi M, Lonati V, et al. FOLFIRINOX-based neoadjuvant therapy in borderline resectable or unresectable pancreatic cancer: a meta-analytical review of published studies. Pancreas. 2015;44(4):515–521. doi: 10.1097/MPA.0000000000000314.
    1. Ferrone CR, Marchegiani G, Hong TS, Ryan DP, Deshpande V, McDonnell EI, et al. Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg. 2015;261(1):12–17. doi: 10.1097/SLA.0000000000000867.
    1. Pietrasz D, Marthey L, Wagner M, Blanc JF, Laurent C, Turrini O, et al. Pathologic major response after FOLFIRINOX is prognostic for patients secondary resected for borderline or locally advanced pancreatic adenocarcinoma: an AGEO-FRENCH, prospective, multicentric cohort. Ann Surg Oncol. 2015;22(Suppl 3):1196–1205. doi: 10.1245/s10434-015-4783-x.
    1. Serrano PE, Cleary SP, Dhani N, Kim PT, Greig PD, Leung K, et al. Improved long-term outcomes after resection of pancreatic adenocarcinoma: a comparison between two time periods. Ann Surg Oncol. 2015;22(4):1160–1167. doi: 10.1245/s10434-014-4196-2.
    1. Hata T, Motoi F, Ishida M, Naitoh T, Katayose Y, Egawa S, et al. Effect of hospital volume on surgical outcomes after pancreaticoduodenectomy: a systematic review and meta-analysis. Ann Surg. 2016;263(4):664–672. doi: 10.1097/SLA.0000000000001437.
    1. Pugalenthi A, Protic M, Gonen M, Kingham TP, Angelica MI, Dematteo RP, et al. Postoperative complications and overall survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. J Surg Oncol. 2016;113(2):188–193. doi: 10.1002/jso.24125.
    1. Louvet C, Labianca R, Hammel P, Lledo G, Zampino MG, Andre T, et al. Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol. 2005;23(15):3509–3516. doi: 10.1200/JCO.2005.06.023.
    1. Rocha Lima CM, Green MR, Rotche R, Miller WH, Jr, Jeffrey GM, Cisar LA, et al. Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate. J Clin Oncol. 2004;22(18):3776–3783. doi: 10.1200/JCO.2004.12.082.
    1. Conroy T, Bachet JB, Ayav A, Huguet F, Lambert A, Caramella C, et al. Current standards and new innovative approaches for treatment of pancreatic cancer. Eur J Cancer. 2016;57:10–22. doi: 10.1016/j.ejca.2015.12.026.
    1. Pietryga JA, Morgan DE. Imaging preoperatively for pancreatic adenocarcinoma. J Gastrointest Oncol. 2015;6(4):343–357.
    1. Bockhorn M, Uzunoglu FG, Adham M, Imrie C, Milicevic M, Sandberg AA, et al. Borderline resectable pancreatic cancer: a consensus statement by the International Study Group of Pancreatic Surgery (ISGPS) Surgery. 2014;155(6):977–988. doi: 10.1016/j.surg.2014.02.001.

Source: PubMed

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