Modified FLOT Chemotherapy as First-line Treatment in Advanced or Metastatic Gastric Cancer
Phase: PHASE1
Conditions: Gastric Cancer
Sponsor: Ruijin Hospital

Title：mFLOT Chemotherapy as First-line Treatment in GC 
NCT: NCT03606928 
Date:2018/05/02 
 
Patient eligibility  
Chinese patients with metastatic gastric cancer were eligible if all the following criteria were met: 
histologically confirmed adenocarcinoma of stomach; untreated metastatic disease or recurrence over 6 
months after finish of adjuvant chemotherapy; age from 18 to 75 years; Eastern Cooperative Oncology 
Group (ECOG) performance status of 0-2; estimated life expectancy more than 3 months; adequate 
hematological, hepatic, renal and coagulation function (White blood count ≥3.5×109/L, Absolute 
neutrophil count ≥1.5×109/L, Platelets ≥80×109/L, Hemoglobin≥75g/L). Exclusion criteria were: second 
primary malignant disease, central nervous system metastasis, peripheral nerve disease, uncontrollable 
medical illness, contraindication or known hypersensitivity reaction to any of the study drugs, patients 
with pregnant. All patients provided written informed consents. The protocol was approved by ethics 
committee of Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s 
Republic of China.  
 
Treatment plan 
Classical 3+3 design was used in present study. The starting doses of docetaxel and oxaliplatin were 
at 80% of original doses of FLOT regimen. Dose escalation started at 40mg/m2 of docetaxel (level 
1) and 65mg/m2 of oxaliplatin (level 1). The plan of dose escalation was listed in Table 1. The 
increment doses of docetaxel and oxaliplatin were about 10% of highest doses, respectively. At least 

3 patients were enrolled at each dose level. If no patient experienced DLT, the dosage was increased to 
next level and 3 new patients were enrolled. If DLTs occurred in one patient, another 3 patients were 
enrolled in this level. MTD was defined as if 2 or more patients in one level suffered DLTs (two of three 
patients or two of six patients). The RD was defined as the dose level below the MTD.   
Leucovorin (200mg/m2) and 5-FU (2200mg/m2 48 hours continuous infusion) were given in fixed 
dose. Antiemetic prophylaxis could be given before treatment. Dexamethasone was administered orally 
before and after treatment of docetaxel following the protocol to prevent fluid retention and allergic 
reactions. Prophylactic use of G-CSF was not permitted. The treatment was administered every 2 weeks 
until disease progression, unacceptable toxicity, patient’s refusal or maximum 12 cycles. If patients were 
evaluated as SD or better after 8 cycles, S-1 as maintenance therapy or another 4 cycles intravenous 
treatment could be given decided by physicians and patients together.  
  Dose modification was not permitted in first two cycles unless severe adverse events occurred. Dose 
reductions were performed for all three drugs when treatment related grade 3 or 4 toxicities occurred 
after first two cycles. The dose of docetaxel, oxaliplatin and fluorouracil were reduced by 20% for the 
subsequent cycle. Dose reduction could be performed only once. If grade 3 or 4 toxicities still occurred 
after dose reduction, drug which caused distinction toxicities would be excluded in following treatment. 
Treatment initiated when following criteria was met, absolute granulocyte count was ≥ 1.5×109/L, 
platelet count was ≥ 100×109/L, and all treatment related toxicities were resolved to grade ≤1.  
 
Toxicity evaluation 
Adverse events were recorded and evaluated every week during the first two cycles according to the 
National Cancer Instituted Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 

4.0), and every 2 weeks after. Dose-limiting toxicities (DLTs) were determined during the first two cycles, 
including: febrile neutropenia, grade 4 neutropenia, grade 4 thrombocytopenia, ≥grade 3 infection, 
≥grade 3 non-hematological toxicities, treatment delay ≥ 2 weeks[9].  
 
Response evaluation  
Response were classified according to the RECIST guideline (version 1.1)[10]. Enhanced computed 
tomography scans of chest, abdomen and pelvis were performed within 1 week before start of the 
treatment and were repeated every 8 weeks irrespective of treatment delay. If clinical symptoms, like 
increasing ascites, worse of pain, which indicated progression of disease during treatment, the 
imaging examination would be performed ahead of schedule decided by physicians to assess status 
of disease. Progression free survival (PFS) was measured from the date of treatment start until disease 
progression or death of any cause. Overall survival (OS) was measured from the date of diagnosis 
until death of any cause.