Feasibility and Safety of Perioperative Chemotherapy With Fluorouracil Plus Leucovorin, Oxaliplatin, and Docetaxel for Locally Advanced Gastric Cancer Patients in China

Birendra Kumar Sah, Wei Xu, Benyan Zhang, Huan Zhang, Fei Yuan, Jian Li, Wentao Liu, Chao Yan, Chen Li, Min Yan, Zhenggang Zhu, Birendra Kumar Sah, Wei Xu, Benyan Zhang, Huan Zhang, Fei Yuan, Jian Li, Wentao Liu, Chao Yan, Chen Li, Min Yan, Zhenggang Zhu

Abstract

Background: Neoadjuvant fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) has shown significant benefits for gastric cancer patients. However, it has not been well accepted in Asian countries. We conducted a prospective study on the safety and feasibility of the FLOT regimen in Chinese patients.

Methods: Patients with adenocarcinoma of the stomach or esophagogastric junction received four cycles of neoadjuvant chemotherapy (NAC) and four cycles of adjuvant chemotherapy (AC) with the FLOT regimen. The completion status of chemotherapy, adverse events, postoperative morbidities, and pathological tumor regression were analyzed. The 2-year overall survival (OS) and relapse-free survival are presented.

Results: Altogether, 10 patients were enrolled, and all patients completed four cycles of neoadjuvant chemotherapy. There were no severe hematological adverse events (grade 3 or above), except for a case of grade 3 anemia. All 10 patients underwent radical gastrectomy. Nine patients had R0 resection, and three patients had complete or subtotal pathological tumor regression. Nine patients completed four cycles of adjuvant chemotherapy, but only one patient completed the full dose of adjuvant chemotherapy. The dose of adjuvant chemotherapy was reduced by 25% or less in the other patients. The median follow-up time was 23.13 months, eight patients achieved the overall survival endpoint, and seven patients had relapse-free survival for this period. Two patients died of disease progression.

Conclusions: Our study demonstrates that the neoadjuvant FLOT regimen is safe and effective for Chinese patients. Dose adjustment is necessary for adjuvant chemotherapy. The pathological regression and survival rates need reevaluation in a larger cohort. The trial is registered with ClinicalTrials.gov (number NCT03646591).

Keywords: FLOT regimen; TRG; adjuvant chemotherapy; gastric cancer; neoadjuvant chemotherapy.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Sah, Xu, Zhang, Zhang, Yuan, Li, Liu, Yan, Li, Yan and Zhu.

Figures

Figure 1
Figure 1
Kaplan-Meier (K-M) Plot for overall survival (OS) and relapse-free survival (RFS). (A) K-M plot for OS. (B) K-M plot for RFS.

References

    1. Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med (2006) 355(1):11–20. 10.1056/NEJMoa055531
    1. Schuhmacher C, Gretschel S, Lordick F, Reichardt P, Hohenberger W, Eisenberger CF, et al. 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 (2010) 28(35):5210–8. 10.1200/JCO.2009.26.6114
    1. Yoshikawa T, Sasako M, Yamamoto S, Sano T, Imamura H, Fujitani K, et al. Phase II study of neoadjuvant chemotherapy and extended surgery for locally advanced gastric cancer. Br J Surg (2009) 96(9):1015–22. 10.1002/bjs.6665
    1. Iwasaki Y, Sasako M, Yamamoto S, Nakamura K, Sano T, Katai H, et al. Phase II study of preoperative chemotherapy with S-1 and cisplatin followed by gastrectomy for clinically resectable type 4 and large type 3 gastric cancers (JCOG0210). J Surg Oncol (2013) 107(7):741–5. 10.1002/jso.23301
    1. Katayama H, Tsuburaya A, Mizusawa J, Nakamura K, Katai H, Imamura H, et al. An integrated analysis of two phase II trials (JCOG0001 and JCOG0405) of preoperative chemotherapy followed by D3 gastrectomy for gastric cancer with extensive lymph node metastasis. Gastric Cancer (2019) 22(6):1301–7. 10.1007/s10120-019-00981-5
    1. Terashima M, Iwasaki Y, Mizusawa J, Katayama H, Nakamura K, Katai H, et al. Randomized phase III trial of gastrectomy with or without neoadjuvant S-1 plus cisplatin for type 4 or large type 3 gastric cancer, the short-term safety and surgical results: Japan Clinical Oncology Group Study (JCOG0501). Gastric Cancer (2019) 22(5):1044–52. 10.1007/s10120-019-00941-z
    1. Okabe H, Hata H, Ueda S, Zaima M, Tokuka A, Yoshimura T, et al. A phase II study of neoadjuvant chemotherapy with S-1 and cisplatin for stage III gastric cancer: KUGC03. J Surg Oncol (2016) 113(1):36–41. 10.1002/jso.24096
    1. Eto K, Hiki N, Kumagai K, Shoji Y, Tsuda Y, Kano Y, et al. Prophylactic effect of neoadjuvant chemotherapy in gastric cancer patients with postoperative complications. Gastric Cancer (2018) 21(4):703–9. 10.1007/s10120-017-0781-y
    1. Ito S, Sano T, Mizusawa J, Takahari D, Katayama H, Katai H, et al. A phase II study of preoperative chemotherapy with docetaxel, cisplatin, and S-1 followed by gastrectomy with D2 plus para-aortic lymph node dissection for gastric cancer with extensive lymph node metastasis: JCOG1002. Gastric Cancer (2017) 20(2):322–31. 10.1007/s10120-016-0619-z
    1. Group G, Paoletti X, Oba K, Burzykowski T, Michiels S, Ohashi Y, et al. Benefit of adjuvant chemotherapy for resectable gastric cancer: a meta-analysis. JAMA (2010) 303(17):1729–37. 10.1001/jama.2010.534
    1. Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, et al. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet (2012) 379(9813):315–21. 10.1016/S0140-6736(11)61873-4
    1. Lee J, Lim DH, Kim S, Park SH, Park JO, Park YS, et al. Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: the ARTIST trial. J Clin Oncol (2012) 30(3):268–73. 10.1200/JCO.2011.39.1953
    1. Noh SH, Park SR, Yang HK, Chung HC, Chung IJ, Kim SW, et al. Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): 5-year follow-up of an open-label, randomised phase 3 trial. Lancet Oncol (2014) 15(12):1389–96. 10.1016/S1470-2045(14)70473-5
    1. Lorenzen S, Thuss-Patience P, Al-Batran SE, Lordick F, Haller B, Schuster T, et al. Impact of pathologic complete response on disease-free survival in patients with esophagogastric adenocarcinoma receiving preoperative docetaxel-based chemotherapy. Ann Oncol (2013) 24(8):2068–73. 10.1093/annonc/mdt141
    1. Ronellenfitsch U, Schwarzbach M, Hofheinz R, Kienle P, Kieser M, Slanger TE, et al. Perioperative chemo(radio)therapy versus primary surgery for resectable adenocarcinoma of the stomach, gastroesophageal junction, and lower esophagus. Cochrane Database Syst Rev (2013) (5):CD008107. 10.1002/14651858.CD008107.pub2
    1. Al-Batran SE, Hofheinz RD, Pauligk C, Kopp HG, Haag GM, Luley KB, 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) 17(12):1697–708. 10.1016/S1470-2045(16)30531-9
    1. Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, 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) 393(10184):1948–57. 10.1016/S0140-6736(18)32557-1
    1. Coccolini F, Nardi M, Montori G, Ceresoli M, Celotti A, Cascinu S, et al. Neoadjuvant chemotherapy in advanced gastric and esophago-gastric cancer. Meta-analysis of randomized trials. Int J Surg (2018) 51:120–7. 10.1016/j.ijsu.2018.01.008
    1. Fazio N, Biffi R, Maibach R, Hayoz S, Thierstein S, Brauchli P, et al. Preoperative versus postoperative docetaxel-cisplatin-fluorouracil (TCF) chemotherapy in locally advanced resectable gastric carcinoma: 10-year follow-up of the SAKK 43/99 phase III trial. Ann Oncol (2016) 27(4):668–73. 10.1093/annonc/mdv620
    1. Zhou C, Ma T, Shi M, Xi W, Wu J, Yang C, et al. Dose-finding study of modified FLOT (mFLOT) regimen as first-line treatment in Chinese patients with metastatic adenocarcinoma of stomach. Cancer Chemother Pharmacol (2020) 85(1):113–9. 10.1007/s00280-019-03982-4
    1. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer (2009) 45(2):228–47. 10.1016/j.ejca.2008.10.026
    1. Becker K, Mueller JD, Schulmacher C, Ott K, Fink U, Busch R, et al. Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy. Cancer (2003) 98(7):1521–30. 10.1002/cncr.11660
    1. Sah BK, Chen MM, Yan M, Zhu ZG. Gastric cancer surgery: Billroth I or Billroth II for distal gastrectomy? BMC Cancer (2009) 9:428. 10.1186/1471-2407-9-428
    1. Sah BK, Chen MM, Yan M, Zhu ZG. Reoperation for early postoperative complications after gastric cancer surgery in a Chinese hospital. World J Gastroenterol (2010) 16(1):98–103. 10.3748/wjg.v16.i1.98

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