Efficacy of perioperative FOLFIRINOX chemotherapy versus FLOT chemotherapy in patients with resectable adenocarcinoma of the stomach or gastroesophageal junction (SIEWERT types II–III, cT4aN0M0, T1–4cN+ cM0): preliminary results of the study
https://doi.org/10.18027/2224-5057-2023-13-4-7-17
Abstract
Introduction: The main current approach to the treatment of patients with resectable cancer of the stomach and gastroesophageal junction (GEJ) is perioperative FLOT chemotherapy. The mFOLFIRINOX regimen has been shown to be effective and safe in disseminated adenocarcinoma of the stomach and GEJ. This article presents preliminary results of the efficacy and safety assessment of perioperative FOLFIRINOX chemotherapy in patients with resectable cancer of the stomach and gastroesophageal junction.
Materials and Methods: The FOLFIRINOX / FLOT study is a phase 2 / 3 open-label, randomized trial. Study enrollment was started in January 2019 and is currently ongoing. The inclusion criteria are: histologically confirmed resectable adenocarcinoma of the stomach or gastroesophageal junction, Siewert types II–III, clinical stage cT4aN0M0, cT1–4N1–3M0 or cT2–4N0–3M0, with total or subtotal involvement of the stomach. The following regimens were used for perioperative chemotherapy: FLOT — docetaxel 50 mg / m2 on day 1, oxaliplatin 85 mg / m2 on day 1, leucovorin 200 mg / 2 on day 1, 5FU 2600 mg / m2 × 24 hours starting on day 1, or mFOLFIRINOX — irinotecan 180 mg / m2 on day 1, oxaliplatin 85 mg / 2 on day 1, leucovorin 200 mg / m2 on day 1, 5FU 250 mg / m2 bolus on day 1 and then 2200 mg / m2 × 48 hours on day 1. The primary endpoint was 5‑year overall survival.
Results: All planned preoperative courses of chemotherapy had been administered to 25 (86 %) patients in the FLOT group (n = 29) and 22 (92 %) patients in the FOLFIRINOX group (n = 24). Four (12 %) and 2 (8 %) patients in the FLOT and FOLFIRINOX groups, respectively, discontinued the treatment. The surgical staging was used in 48 patients (91 %) (25 [86 %] in the FLOT group and 23 [96 %] in the FOLFIRINOX group). Complete tumor regression (Mandard grade 1) had been achieved in 4 patients (2 [7 %] in the FLOT group and 2 [8 %] in the FOLFIRINOX group). Postoperative complications were detected in 2 patients (8 %) in the FLOT group and 4 (17 %) in the FOLFRIRNOX group. Thirty-three patients (62 %) received all scheduled postoperative treatment courses (n = 19, 66 % for FLOT and n = 14, 58 % for FOLFIRINOX).
Conclusions: The preliminary results of the FOLFIRINOX / FLOT study showed comparable tolerability of the regimens and comparable complete pathological response rates. However, there was a higher incidence of postoperative complications detected among patients who received the FOLFIRINOX regimen compared to the FLOT group.
About the Authors
A. E. KalininRussian Federation
Alexey E. Kalinin, MD, PhD, Senior Researcher
Moscow
I. G. Avdyukhin
Russian Federation
Ivan G. Avdyukhin, postgraduate student
Moscow
S. N. Nered
Russian Federation
Sergei N. Nered, MD, PhD, DSc, Senior Research Scientist
Moscow
N. S. Besova
Russian Federation
Natalia S. Besova, MD, PhD, Senior Research Scientist
Moscow
A. A. Tryakin
Russian Federation
Alexey A. Tryakin, MD, PhD, DSc, Deputy Director for Research, Head of Medical Oncology (Chemotherapy) Department No. 2
Moscow
E. V. Artamonova
Russian Federation
Elena V. Artamonova, MD, PhD, DSc, Head of the Department
Moscow
T. A. Titova
Russian Federation
Tatiana А. Titova, MD, PhD, oncologist
Moscow
E. S. Obarevich
Russian Federation
Ekaterina S. Obarevich, oncologist, Chemotherapy Department
Moscow
E. O. Ignatova
Russian Federation
Ekaterina O. Ignatova, MD, PhD, Researcher
Moscow
N. A. Kozlov
Russian Federation
Nikolay A. Kozlov, MD, PhD, pathologist
Moscow
O. V. Rossomakhina
Russian Federation
Olesya M. Rossomahina, Senior Lecturer
Lugansk, Lugansk People’s Republic
N. A. Shishkina
Russian Federation
Nina A. Shishkina, radiologist
Moscow
E. S. Kolobanova
Russian Federation
Evgeniya S. Kolobanova, Researcher
Moscow
O. A. Malikhova
Russian Federation
Olga А. Malikhovа, MD, PhD, DSc, Head of the Department
Moscow
M. G. Abgaryan
Russian Federation
Mikael G. Abgaryan, MD, PhD, Senior Researcher
Moscow
M. P. Nikulin
Russian Federation
Maksim P. Nikulin, MD, PhD, Senior Researcher
Moscow
P. P. Arkhiri
Russian Federation
Petr P. Arkhiri, MD, PhD, oncologist
Moscow
L. A. Vashakmadze
Russian Federation
Levan А. Vashakmadze, MD, PhD, DSc, Professor, Senior Research Advisor
Moscow
I. N. Peregorodiev
Russian Federation
Ivan N. Peregorodiev, MD, PhD, oncologist
Moscow
E. A. Suleimanov
Russian Federation
Elkhan A. Suleimanov, MD, PhD, Minister of Health of the Chechen Republic
Grozny
I. S. Stilidi
Russian Federation
Ivan S. Stilidi, Academician of the Russian Academy of Sciences, MD, PhD, DSc, Professor, Director
Moscow
References
1. Al-Batran SE, Homann N, Pauligk C. et al. 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. 2019 May 11 ; 393 (10179) : 1948–1957. doi: 10.1016/S0140-6736(18)32557-1. Epub 2019 Apr 11. PMID: 30982686.
2. Al-Batran SE, Hofheinz RD, Pauligk C et al. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO) : results from the phase 2 part of a multicentre, open-label, randomised phase 2 / 3 trial. Lancet Oncol. 2016 Dec ; 17 (12) : 1697–1708. doi: 10.1016/S1470-2045(16)30531-9. Epub 2016 Oct 22. PMID: 27776843.
3. Stark AP, Ikoma N, Chiang YJ et al. Characteristics and Survival of Gastric Cancer Patients with Pathologic Complete Response to Preoperative Therapy. Ann Surg Oncol. 2019 Oct ; 26 (11) : 3602–3610. doi: 10.1245/s10434-019-07638-8. Epub 2019 Jul 26. PMID: 31350645.
4. Mandard AM, Dalibard F, Mandard JC, Marnay J, Henry-Amar M, Petiot JF, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer. 1994 ; 73 : 2680–6.
5. Lauren P. The two histological main types of gastric carcinoma : diff use and so-called intestinal-type carcinoma. An attempt at a histo-clinical classifi cation. Acta Pathol Microbiol Scand 1965 ; 64 : 31–49.
6. Dindo D, Demartines N, Clavien PA. Classification of surgical complications : a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004 ; 240 (2) : 205–213.
7. Ferlay J., Soerjomataram I., Dikshit R., Eser S., Mathers C., Rebelo M. et al. Cancer incidence and mortality worldwide : sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015 ; 136 : E359–86).
8. Cunningham D, Allum WH, Stenning SP, Thompson JN, et al.Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006 ; 355 : 11–20.
9. Ychou,M, Boige, V, Pignon,J-P, Conroy T,et al. Perioperative Chemotherapy Compared With Surgery Alone for Resectable Gastroesophageal Adenocarcinoma : An FNCLCC and FFCD Multicenter Phase III Trial. J Clin Oncol 29 : 1715–1721).
10. Трусилова, Е. Эффективность и токсичность химиотерапии по схеме FOLFIRINOX у больных диссеминированным раком желудка. Предварительные результаты / Е.В. Трусилова, Н.С. Бесова, В.А. Горбунова и др. // Эффективная фармакотерапия. Онкология, гематология, радиология .– 2013 .– Т. 46 (4) .– С. 6–13.
11. International Union Against Cancer (UICC). TNM Classification of Malignant Tumours, 7th ed. Sobin L.H., Gospodarowicz M.K., Wittekind Ch., eds. New York : Wiley-Blackwell ; 2009.
Review
For citations:
Kalinin A.E., Avdyukhin I.G., Nered S.N., Besova N.S., Tryakin A.A., Artamonova E.V., Titova T.A., Obarevich E.S., Ignatova E.O., Kozlov N.A., Rossomakhina O.V., Shishkina N.A., Kolobanova E.S., Malikhova O.A., Abgaryan M.G., Nikulin M.P., Arkhiri P.P., Vashakmadze L.A., Peregorodiev I.N., Suleimanov E.A., Stilidi I.S. Efficacy of perioperative FOLFIRINOX chemotherapy versus FLOT chemotherapy in patients with resectable adenocarcinoma of the stomach or gastroesophageal junction (SIEWERT types II–III, cT4aN0M0, T1–4cN+ cM0): preliminary results of the study. Malignant tumours. 2023;13(4):7-17. (In Russ.) https://doi.org/10.18027/2224-5057-2023-13-4-7-17