Efficacy and tolerability of fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) in unselected patients with advanced gastric and gastroesophageal cancer: does age really matter?
ECOG
Elderly patients
FLOT regime
Gastric cancer
Gastroesophageal cancer
Journal
Journal of cancer research and clinical oncology
ISSN: 1432-1335
Titre abrégé: J Cancer Res Clin Oncol
Pays: Germany
ID NLM: 7902060
Informations de publication
Date de publication:
May 2023
May 2023
Historique:
received:
25
03
2022
accepted:
02
06
2022
medline:
14
4
2023
pubmed:
29
6
2022
entrez:
28
6
2022
Statut:
ppublish
Résumé
Fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) regimen has shown strong efficacy as perioperative therapy for patients with locally advanced gastric (GC) and gastroesophageal (AEG) carcinoma. In the palliative situation, FLOT is recommended only for young fit patients. Data of efficacy and tolerability of FLOT in elderly patients are scarce and controversial. Thus, this study aimed to provide real-life experience of elderly patients with GC and AEG treated with FLOT as first-line palliative chemotherapy. Patients with advanced or metastatic GC or AEG and treated with FLOT as first-line palliative therapy between 2010 and 2021 were analyzed. Patients were grouped into < 65 years old (n = 35) and ≥ 65 years old (n = 22) groups. Overall survival (OS), progression-free survival (PFS), feasibility and toxicity were analyzed. The median OS was 10.4 months with no significant difference between both groups (HR 0.86; 95% CI 0.48, 1.57; p = 0.632). The ECOG performance status showed powerful influence on OS in the subgroup analysis with median OS of 12.3 months for ECOG = 0 compared to 5.0 months for ECOG ≥ 1 (p = 0.015) as well as in multivariate analysis (HR 2.62; 95% CI 1.36, 5.04; p = 0.004). In the present study the ECOG performance status showed a stronger prognostic value than patient age in FLOT as first- line therapy in a real-life cohort with advanced and metastatic GC and AEG. The performance status should therefore be considered in the therapeutic decision making of elderly patients with GC and AEG.
Identifiants
pubmed: 35763109
doi: 10.1007/s00432-022-04109-8
pii: 10.1007/s00432-022-04109-8
doi:
Substances chimiques
Docetaxel
15H5577CQD
Leucovorin
Q573I9DVLP
Oxaliplatin
04ZR38536J
Fluorouracil
U3P01618RT
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1849-1862Subventions
Organisme : Deutsche Krebshilfe
ID : 109255
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Références
Al-Batran S, Hartmann J, Hofheinz R, Homann N, Rethwisch V, Probst S, Stoehlmacher J, Clemens MR, Mahlberg R, Fritz M, Seipelt G, Sievert M, Pauligk C, Atmaca A, Jäger E (2008) Biweekly fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) for patients with metastatic adenocarcinoma of the stomach or esophagogastric junction: a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol 19(11):1882–1887. https://doi.org/10.1093/annonc/mdn403
doi: 10.1093/annonc/mdn403
pubmed: 18669868
Al-Batran S et al (2017) Effect of neoadjuvant chemotherapy followed by surgical resection on survival in patients with limited metastatic gastric or gastroesophageal junction cancer: the AIO-FLOT3 trial. JAMA Oncol 3(9):1237–1244. https://doi.org/10.1001/jamaoncol.2017.0515
doi: 10.1001/jamaoncol.2017.0515
pubmed: 28448662
pmcid: 5824287
Al-Batran S et al (2019) Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet (london, England) 393(10184):1948–1957. https://doi.org/10.1016/S0140-6736(18)32557-1
doi: 10.1016/S0140-6736(18)32557-1
pubmed: 30982686
Al-Batran S, Moorahrend E, Maintz C, Goetze T, Hempel D, Thuss-Patience P, Gaillard V, Hegewisch-Becker S (2020) Clinical practice observation of trastuzumab in patients with human epidermal growth receptor 2-positive metastatic adenocarcinoma of the stomach or gastroesophageal junction. Oncologist 25(8):e1181–e1187. https://doi.org/10.1634/theoncologist.2020-0109
doi: 10.1634/theoncologist.2020-0109
pubmed: 32311799
pmcid: 7418356
Al-Batran S, Pauligk C, Homann N, Hartmann J, Moehler M, Probst S, Rethwisch V, Stoehlmacher-Williams J, Prasnikar N, Hollerbach S, Bokemeyer C, Mahlberg R, Hofheinz R, Luley K, Kullmann F, Jäger E (2013) The feasibility of triple-drug chemotherapy combination in older adult patients with oesophagogastric cancer: a randomised trial of the Arbeitsgemeinschaft Internistische Onkologie (FLOT65+). Eur J Cancer (oxford, England: 1990). https://doi.org/10.1016/j.ejca.2012.09.025
doi: 10.1016/j.ejca.2012.09.025
Anter AH, Abdel-Latif RM (2013) The safety and efficacy of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) combination in the front-line treatment for patients with advanced gastric or gastroesophageal adenocarcinoma: phase II trial. Med Oncol 30(1):451. https://doi.org/10.1007/s12032-012-0451-1
doi: 10.1007/s12032-012-0451-1
pubmed: 23307258
Arnold M, Laversanne M, Brown L, Devesa S, Bray F (2017) Predicting the future burden of esophageal cancer by histological subtype: international trends in incidence up to 2030. Am J Gastroenterol 112(8):1247–1255. https://doi.org/10.1038/ajg.2017.155
doi: 10.1038/ajg.2017.155
pubmed: 28585555
Bang Y, Cutsem V, Feyereislova A, Chung H, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang Y (2010) Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 376(9742):687–697. https://doi.org/10.1016/S0140-6736(10)61121-X
doi: 10.1016/S0140-6736(10)61121-X
pubmed: 20728210
Buas M, Vaughan T (2013) Epidemiology and risk factors for gastroesophageal junction tumors: understanding the rising incidence of this disease. Semin Radiat Oncol 23(1):3–9. https://doi.org/10.1016/j.semradonc.2012.09.008
doi: 10.1016/j.semradonc.2012.09.008
pubmed: 23207041
pmcid: 3535292
Cunningham D, Allum W, Stenning SP, Thompson JN, Van de Velde C, Nicolson M, Scarffe H, Lofts F, Falk S, Iveson T, Smith D, Langley R, Verma M, Weeden S, Chua YJ, Trial Participants MAGIC (2006) Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 355(1):11–20. https://doi.org/10.1056/NEJMoa055531
doi: 10.1056/NEJMoa055531
pubmed: 16822992
Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR, Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom (2008) Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 358 (1): 36–46. https://doi.org/10.1056/NEJMoa073149
Epistola RJ, Chao J (2020) Systemic therapy for advanced gastroesophageal cancers: progress and pitfalls. Transl Gastroenterol Hepatol. https://doi.org/10.21037/tgh.2020.01.10
doi: 10.21037/tgh.2020.01.10
pubmed: 33073048
pmcid: 7530312
Gong J, Liu T, Fan Q, Bai L, Bi F, Qin S, Wang J, Xu N, Cheng Y, Ba Y, Liu W, Wang L, Shen L (2016) Optimal regimen of trastuzumab in combination with oxaliplatin/ capecitabine in first-line treatment of HER2-positive advanced gastric cancer (CGOG1001): a multicenter, phase II trial. BMC Cancer 16(1):68. https://doi.org/10.1186/s12885-016-2092-9
doi: 10.1186/s12885-016-2092-9
pubmed: 26857702
pmcid: 4746787
Gürler F, İlhan A, Güven DC, Turhan O, Kurt İnci B, Sütçüoğlu O, Yildiz F, Arik Z, Öksüzoğlu B, Yalçin Ş, Özdemir N, Yazici O, Özet A (2022) Does docetaxel matter in metastatic gastric cancer? FOLFOX versus FLOT regimens as first-line treatment. Anticancer Drugs 33(1):e477. https://doi.org/10.1097/CAD.0000000000001143
doi: 10.1097/CAD.0000000000001143
pubmed: 34261917
Hall PS, Lord SR, Collinson M, Marshall H, Jones M, Lowe C, Howard H, Swinson D, Velikova G, Anthoney A, Roy R, Dent J, Cheeseman S, Last K, Seymour MT (2017) A randomised phase II trial and feasibility study of palliative chemotherapy in frail or elderly patients with advanced gastroesophageal cancer (321GO). Br J Cancer 116(4):472–478. https://doi.org/10.1038/bjc.2016.442
doi: 10.1038/bjc.2016.442
pubmed: 28095397
pmcid: 5318975
Janjigian YY et al (2021) First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet 398(10294):27–40. https://doi.org/10.1016/S0140-6736(21)00797-2
doi: 10.1016/S0140-6736(21)00797-2
pubmed: 34102137
pmcid: 8436782
Jimenez-Fonseca P et al (2021) External validity of docetaxel triplet trials in advanced gastric cancer: are there patients who still benefit? Gastric Cancer 24(2):445–456. https://doi.org/10.1007/s10120-020-01116-x
doi: 10.1007/s10120-020-01116-x
pubmed: 32970266
Knödler M, Körfer J, Kunzmann V, Trojan J, Daum S, Schenk M, Kullmann F, Schroll S, Behringer D, Stahl M, Al-Batran S, Hacker U, Ibach S, Lindhofer H, Lordick F (2018) Randomised phase II trial to investigate catumaxomab (anti-EpCAM × anti-CD3) for treatment of peritoneal carcinomatosis in patients with gastric cancer. Br J Cancer 119(3):296–302. https://doi.org/10.1038/s41416-018-0150-6
doi: 10.1038/s41416-018-0150-6
pubmed: 29988111
pmcid: 6070920
Krebs in Deutschland für 2015/2016 (2019) 12. Ausgabe. Robert Koch-Institut (Hrsg) und die Gesellschaft der epidemiologischen Krebsregister in Deutschland e.V. (Hrsg), Berlin, https://doi.org/10.25646/5977.3
Kripp M, Al-Batran SE, Rosowski J, Pauligk C, Homann N, Hartmann JT, Moehler M, Hofheinz RD (2014) Quality of life of older adult patients receiving docetaxel-based chemotherapy triplets for esophagogastric adenocarcinoma: a randomized study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Gastric Cancer. https://doi.org/10.1007/s10120-013-0242-1
doi: 10.1007/s10120-013-0242-1
pubmed: 23455717
Liu M, Hu G, Wang Y, Guo J, Liu L, Han X, Wang Z (2018) Comparison of FOLFOX and DOF regimens as first-line treatment in East Asian patients with advanced gastric cancer. Onco Targets Ther 11:375–381. https://doi.org/10.2147/OTT.S149624
doi: 10.2147/OTT.S149624
pubmed: 29398919
pmcid: 5775733
Merchant SJ, Kong W, Gyawali B, Hanna TP, Chung W, Nanji S, Patel SV, Booth CM (2021) First-line palliative chemotherapy for esophageal and gastric cancer: practice patterns and outcomes in the general population. JCO Oncol Pract 17(10):e1537–e1550. https://doi.org/10.1200/OP.20.00397
doi: 10.1200/OP.20.00397
pubmed: 33449833
Ronellenfitsch U, Schwarzbach M, Hofheinz R, Kienle P, Kieser M, Slanger TE, Burmeister B, Kelsen D, Niedzwiecki D, Schuhmacher C, Urba S, Velde C, Walsh TN, Ychou M, Jensen K (2013) Preoperative chemo (radio)therapy versus primary surgery for gastroesophageal adenocarcinoma: systematic review with meta-analysis combining individual patient and aggregate data. Eur J Cancer 49(15):3149–3158. https://doi.org/10.1016/j.ejca.2013.05.029
doi: 10.1016/j.ejca.2013.05.029
pubmed: 23800671
Rosenberg AJ, Rademaker A, Hochster HS, Ryan T, Hensing T, Shankaran V, Baddi L, Mahalingam D, Mulcahy MF, Benson A (2019) Docetaxel, Oxaliplatin, and 5-Fluorouracil (DOF) in Metastatic and Unresectable Gastric/Gastroesophageal junction adenocarcinoma: a phase II study with long-term follow-up. Oncologist 24(8):1039-e642. https://doi.org/10.1634/theoncologist.2019-0330
doi: 10.1634/theoncologist.2019-0330
pubmed: 31138725
pmcid: 6693711
Ross P, Nicolson M, Cunningham D, Valle J, Seymour M, Harper P, Price T, Anderson H, Iveson T, Hickish T, Lofts F, Norman A (2002) Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer. J Clin Oncol 20(8):1996–2004. https://doi.org/10.1200/JCO.2002.08.105
doi: 10.1200/JCO.2002.08.105
pubmed: 11956258
Schuhmacher C, Gretschel S, Lordick F, Reichardt P, Hohenberger W, Eisenberger CF, Haag C, Mauer ME, Hasan B, Welch J, Ott K, Hoelscher A, Schneider PM, Bechstein W, Wilke H, Lutz MP, Nordlinger B, Cutsem EV, Siewert JR, Schlag PM (2010) Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia: european organisation for research and treatment of cancer randomized trial 40954. J Clin Oncol 28(35):5210–5218. https://doi.org/10.1200/JCO.2009.26.6114
doi: 10.1200/JCO.2009.26.6114
pubmed: 21060024
pmcid: 3020693
Shah MA, Janjigian YY, Stoller R, Shibata S, Kemeny M, Krishnamurthi S, Su YB, Ocean A, Capanu M, Mehrotra B, Ritch P, Henderson C, Kelsen DP (2015) Randomized multicenter phase II study of modified docetaxel, cisplatin, and fluorouracil (DCF) versus DCF plus growth factor support in patients with metastatic gastric adenocarcinoma: a study of the us gastric cancer consortium. J Clin Oncol 33(33):3874–3879. https://doi.org/10.1200/JCO.2015.60.7465
doi: 10.1200/JCO.2015.60.7465
pubmed: 26438119
Swaminathan D, Swaminathan V (2015) Geriatric oncology: problems with under-treatment within this population. Cancer Biol Med 12(4):275–283. https://doi.org/10.7497/j.issn.2095-3941.2015.0081
doi: 10.7497/j.issn.2095-3941.2015.0081
pubmed: 26779364
pmcid: 4706517
Trumper M, Ross PJ, Cunningham D, Norman AR, Hawkins R, Seymour M, Harper P, Iveson T, Nicolson M, Hickish T (2006) Efficacy and tolerability of chemotherapy in elderly patients with advanced oesophago-gastric cancer: a pooled analysis of three clinical trials. Eur J Cancer 42(7):827–834. https://doi.org/10.1016/j.ejca.2005.08.044
doi: 10.1016/j.ejca.2005.08.044
pubmed: 16466913
Van Cutsem E, Sagaert X, Topal B, Haustermans K, Prenen H (2016) Gastric cancer. Lancet (london, England) 388(10060):2654–2664. https://doi.org/10.1016/S0140-6736(16)30354-3
doi: 10.1016/S0140-6736(16)30354-3
pubmed: 27156933
Van Cutsem E, Moiseyenko V. M, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse M, Ajani J. A, and V325 Study Group (2006) Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol 24(31):4991–4997. https://doi.org/10.1200/JCO.2006.06.8429
doi: 10.1200/JCO.2006.06.8429
Wagner AD, Syn NL, Moehler M, Grothe W, Yong WP, Tai B-C, Ho J, Unverzagt S (2017) Chemotherapy for advanced gastric cancer. Cochrane Database Systematic Rev. https://doi.org/10.1002/14651858.CD004064.pub4
doi: 10.1002/14651858.CD004064.pub4
Wang J, Xu R, Li J, Bai Y, Liu T, Jiao S, Dai G, Xu J, Liu Y, Fan N, Shu Y, Ba Y, Ma D, Qin S, Zheng L, Chen W, Shen L (2016) Randomized multicenter phase III study of a modified docetaxel and cisplatin plus fluorouracil regimen compared with cisplatin and fluorouracil as first-line therapy for advanced or locally recurrent gastric cancer. Gastric Cancer 19(1):234–244. https://doi.org/10.1007/s10120-015-0457-4
doi: 10.1007/s10120-015-0457-4
pubmed: 25604851
Webb A, Cunningham D, Scarffe JH, Harper P, Norman A, Joffe JK, Hughes M, Mansi J, Findlay M, Hill A, Oates J, Nicolson M, Hickish T, O’Brien M, Iveson T, Watson M, Underhill C, Wardley A, Meehan M (1997) Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol 15(1):261–267. https://doi.org/10.1200/JCO.1997.15.1.261
doi: 10.1200/JCO.1997.15.1.261
pubmed: 8996151
Ychou M, Boige V, Pignon J, Conroy T, Bouché O, Lebreton G, Ducourtieux M, Bedenne L, Fabre J, Saint-Aubert B, Genève J, Lasser P, Rougier P (2011) Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol 29(13):1715–1721. https://doi.org/10.1200/JCO.2010.33.0597
doi: 10.1200/JCO.2010.33.0597
pubmed: 21444866
Zhou Q, Lan X, Li N, Yuan D, Zhang J (2020) Analysis of prognostic factors and design of prognosis model for patients with stage iv gastric cancer following first-line palliative chemotherapy. Cancer Manag Res 12:10461–10468. https://doi.org/10.2147/CMAR.S263320
doi: 10.2147/CMAR.S263320
pubmed: 33122945
pmcid: 7588669