Perioperative FLOT An Option For Resectable Gastric, GEJ Adenocarcinoma Patients

Phase II trial results support the administration of docetaxel, oxaliplatin, leucovorin and fluorouracil before and after curative surgery in patients with gastric or gastro-oesophageal junction cancer

medwireNews: Among patients with stage II or III resectable gastric or gastro-oesophageal junction (GEJ) cancer, perioperative treatment with the docetaxel -based FLOT regimen significantly increases the likelihood of complete regression compared with anthracycline-based chemotherapy, findings indicate.

Centrally assessed pathological complete regression, defined as no residual tumour cells according to the Becker regression criteria, was achieved by 16% of 128 participants randomly allocated to receive four preoperative and four postoperative 2-week cycles of docetaxel 50 mg/m2, oxaliplatin 85 mg/m2, leucovorin 200 mg/m2 and fluorouracil 2600 mg/m2 over 24 hours (FLOT), all on day 1.

This was significantly higher than the 6% rate among the 137 patients who were given three presurgery and three postsurgery 3-week cycles of epirubicin and cisplatin alongside fluorouracil or capecitabine .

The rate of complete and subtotal (<10% residual tumour cells) regression was also significantly higher in the FLOT than the control arm, at 37% versus 23%.

Reporting on the phase II part of the FLOT4 trial, Salah-Eddin Al-Batran, from the UCT University Cancer Center in Frankfurt am Main, Germany, and colleagues note that the observed improvement in regression rates was “probably attributable to a more pronounced activity of FLOT in tumours with intestinal histology”, as defined by the Lauren classification system.

Specifically, the rate of complete and total regression was significantly higher in the FLOT versus the control group among patients with intestinal, but not those with mixed or diffuse, histology.

Twenty-five percent of FLOT-treated patients experienced at least one serious side effect involving a perioperative medical or surgical complication, compared with 40% of those in the control arm.

Neutropenia, leukopenia, nausea, infection, fatigue and vomiting were the most common nonsurgical adverse events of grade 3 or 4, which the study authors say is “in line with previous reports in the perioperative setting.”

Salah-Eddin Al-Batran et al believe that the study “expands the available options” for the treatment of this patient population.

“Perioperative platinum–fluoropyrimidine doublet regimens such as cisplatin and fluorouracil or triplets such [as] epirubicin, cisplatin, and capecitabine remain appropriate, but FLOT represents an additional option for patients (particularly those with intestinal type tumours), for whom the achievement of pathological regression is considered to be important”, they conclude in The Lancet Oncology.

However, commentator Brian Badgwell and co-authors, from The University of Texas MD Anderson Cancer Center in Houston, USA, remain to be convinced about the clinical relevance of the findings in the absence of “data to document patient benefit associated with pathological complete regression or treatment group”.

They note that survival endpoints, such as overall and progression-free survival, will be reported in the phase III part of the trial.

Nonetheless, the commentary authors “fully support the preoperative strategies for this patient population because these strategies compel experts from various disciplines to communicate and develop a consensus strategy before initiation of any therapy. Not only will clinicians of all disciplines benefit from such interactions, but also the patients, who are the true beneficiaries.”


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; Advance online publication 21 October 2016. doi:  

Badgwell B, Blum M, Estrella J, Ajani J. Personalised therapy for localised gastric and gastro-oesophageal adenocarcinoma. Lancet Oncol; Advance online publication 21 October 2016. doi:

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