CC BY-NC-ND 4.0 · South Asian J Cancer 2022; 11(02): 112-117
DOI: 10.1055/s-0041-1733349
Original Article
Gastrointestinal Cancer

An Analysis of Tolerance and Early Survival Outcomes with Perioperative Modified FLOT in Gastric Cancers

Prabhat Bhargava
1   Department of Medical Oncology, Homi Bhabha National Institute (HBNI), Tata Memorial Hospital, Mumbai, Maharashtra, India
,
Sudeep Das
1   Department of Medical Oncology, Homi Bhabha National Institute (HBNI), Tata Memorial Hospital, Mumbai, Maharashtra, India
,
Vikas Ostwal
1   Department of Medical Oncology, Homi Bhabha National Institute (HBNI), Tata Memorial Hospital, Mumbai, Maharashtra, India
,
Sujay Srinivas
1   Department of Medical Oncology, Homi Bhabha National Institute (HBNI), Tata Memorial Hospital, Mumbai, Maharashtra, India
,
Manish Bhandare
2   Department of Gastrointestinal and HPB Surgery, Homi Bhabha National Institute (HBNI), Tata Memorial Hospital, Mumbai, Maharashtra, India
,
Vikram Chaudhari
2   Department of Gastrointestinal and HPB Surgery, Homi Bhabha National Institute (HBNI), Tata Memorial Hospital, Mumbai, Maharashtra, India
,
Munita Bal
3   Department of Pathology, Homi Bhabha National Institute (HBNI), Tata Memorial Hospital, Mumbai, Maharashtra, India
,
Anoop Mantri
1   Department of Medical Oncology, Homi Bhabha National Institute (HBNI), Tata Memorial Hospital, Mumbai, Maharashtra, India
,
Akhil Kapoor
1   Department of Medical Oncology, Homi Bhabha National Institute (HBNI), Tata Memorial Hospital, Mumbai, Maharashtra, India
,
Shailesh V. Shrikhande
2   Department of Gastrointestinal and HPB Surgery, Homi Bhabha National Institute (HBNI), Tata Memorial Hospital, Mumbai, Maharashtra, India
,
Anant Ramaswamy
1   Department of Medical Oncology, Homi Bhabha National Institute (HBNI), Tata Memorial Hospital, Mumbai, Maharashtra, India
› Author Affiliations
Funding None.

Abstract

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Anant Ramaswamy

Purpose Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) is a current standard of care for locoregionally advanced gastric adenocarcinomas. There is limited real world data with regard to the tolerance and efficacy of this regimen.

Materials and Methods This is a retrospective analysis of gastric cancer patients who were offered neoadjuvant perioperative modified FLOT regimen between December 2016 and October 2018, at the Tata Memorial Hospital, Mumbai. Chemotherapy-related side-effects are reported along with overall survival (OS), as calculated by Kaplan-Meier method.

Results Three hundred and forty-three consecutive patients were started on neoadjuvant chemotherapy (NACT) with mFLOT of which 298 patients (87%) completed the planned treatment. A total of 294 patients (86%) underwent curative resection of gastric cancer. Common grade 3 and grade 4 toxicities during NACT were diarrhea in 42 patients (12%) and febrile neutropenia in 27 patients (8%). Toxic death was seen in nine (2.6%) patients. A total of 264 patients (77%) completed planned adjuvant chemotherapy. Common grade 3 and grade 4 toxicities during adjuvant therapy were diarrhea in 42 patients (12%) and febrile neutropenia in 16 patients (6%). With a median follow-up of 19 months, the estimated 2-year median OS was 69.4%.

Conclusion Administration of modified FLOT regimen in locoregionally advanced gastric cancers is feasible in clinical practice with high completion rates, though requiring dose modifications due to the incidence of clinically relevant grade 3 to 5 toxicities. Early outcomes with the regimen are on par with survivals from the FLOT-AIO study.

Note

The study was approved by Institutional Ethics Committee III, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai, India (900711).


Study was performed in accordance with the ethical principles for Medical Research Involving Human Subjects, outlined in the Declaration of Helsinki.


Supplementary Material



Publication History

Article published online:
22 March 2022

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  • References

  • 1 Cunningham D, Allum WH, Stenning SP. et al. MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006; 355 (01) 11-20
  • 2 Shapiro J, van Lanschot JJ, Hulshof MCC. et al. CROSS study group. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol 2015; 16 (09) 1090-1098
  • 3 Bickenbach K, Strong VE. Comparisons of gastric cancer treatments: east vs. west. J Gastric Cancer 2012; 12 (02) 55-62
  • 4 Russo A, Li P, Strong VE. Differences in the multimodal treatment of gastric cancer: east versus west. J Surg Oncol 2017; 115 (05) 603-614
  • 5 Al-Batran S-E, Homann N, Pauligk C. et al. FLOT4-AIO Investigators. 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) 1948-1957
  • 6 Van Cutsem E, Moiseyenko VM, Tjulandin S. et al. V325 Study Group. 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 2006; 24 (31) 4991-4997
  • 7 Shah MA, Janjigian YY, Stoller R. et al. 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 2015; 33 (33) 3874-3879
  • 8 Liu X, Qiu H, Kong P, Zhou Z, Sun X. Gastric cancer, nutritional status, and outcome. OncoTargets Ther 2017; 10: 2107-2114
  • 9 Tezuka T, Hamada C, Ishida H. et al. Phase II clinical study of modified FOLFOX7 (intermittent oxaliplatin administration) plus bevacizumab in patients with unresectable metastatic colorectal cancer-CRAFT study. Invest New Drugs 2013; 31 (05) 1321-1329
  • 10 Moehler M, Gutzler F, Steinmann S. et al. Comparison of a 48-hour infusion of 5-fluorouracil without folinic acid with 24-hour folinic acid/5-fluorouracil in patients with metastatic colorectal cancer refractory to bolus folinic acid/5-fluorouracil. A prospective cohort study. Chemotherapy 2003; 49 (1-2) 85-89
  • 11 Caires-Lima R, Cayres K, Protásio B. et al. Palliative chemotherapy outcomes in patients with ECOG-PS higher than 1. Ecancermedicalscience 2018; 12: 831
  • 12 Raziee HR, Cardoso R, Seevaratnam R. et al. Systematic review of the predictors of positive margins in gastric cancer surgery and the effect on survival. Gastric Cancer 2012; 15 (Suppl. 01) S116-S124
  • 13 Zhu B-Y, Yuan S-Q, Nie R-C. et al. Prognostic factors and recurrence patterns in T4 gastric cancer patients after curative resection. J Cancer 2019; 10 (05) 1181-1188
  • 14 Lorenzen S, Thuss-Patience P, Al-Batran SE. 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 (08) 2068-2073
  • 15 Al-Batran S-E, 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; 17 (12) 1697-1708
  • 16 Noh SH, Park SR, Yang H-K. et al. CLASSIC trial investigators. 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) 1389-1396
  • 17 Park SH, Sohn TS, Lee J. et al. Phase III trial to compare adjuvant chemotherapy with capecitabine and cisplatin versus concurrent chemoradiotherapy in gastric cancer: final report of the adjuvant chemoradiotherapy in stomach tumors trial, including survival and subset analyses. J Clin Oncol 2015; 33 (28) 3130-3136
  • 18 Cats A, Jansen EPM, van Grieken NCT. et al. CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol 2018; 19 (05) 616-628
  • 19 Patil VM, Noronha V, Joshi A. et al. Dihydropyrimidine dehydrogenase mutation in neoadjuvant chemotherapy in head and neck cancers: myth or reality?. South Asian J Cancer 2016; 5 (04) 182-185
  • 20 Sahu A, Ramaswamy A, Ostwal V. Dihydro pyrimidine dehydrogenase deficiency in patients treated with capecitabine based regimens: a tertiary care centre experience. J Gastrointest Oncol 2016; 7 (03) 380-386
  • 21 Liu D, Lu M, Li J. et al. The patterns and timing of recurrence after curative resection for gastric cancer in China. World J Surg Oncol 2016; 14 (01) 305
  • 22 Ikoma N, Chen H-C, Wang X. et al. Recurrence patterns of gastric cancer in the era of preoperative therapy. JCO 2017; 35 (Suppl. 04) 119-119
  • 23 Mokadem I, Dijksterhuis WPM, van Putten M. et al. Recurrence after preoperative chemotherapy and surgery for gastric adenocarcinoma: a multicenter study. Gastric Cancer 2019; 22 (06) 1263-1273