FLOT Regimen Research Articles

Perioperative FLOT in elderly patients with resectable gastric cancer: Subgroup analysis from the observational RealFLOT study.

4548 Background: The treatment strategy for patients with resectable gastric cancer changed in the last few years with perioperative treatments. FLOT regimen (fluorouracil, oxaliplatin, docetaxel) turned out to be feasible and effective, offering significant improvement in survival outcomes. However, the safety profile of triplet therapies for elderly patients deserves a special attention and, consequently, the best treatment strategy for these patients is still debated. Methods: Focusing on the elderly patient population (age ≥65 years), real-world data from patients with resectable gastric or gastro-oesophageal junction (GEJ) adenocarcinoma (T≥2 and/or N+) enrolled in the observational RealFLOT study were collected. Results: A total of 206 patients with resectable gastric or GEJ adenocarcinoma received perioperative FLOT at 15 Italian centers in routine clinical practice, between September 2016 and September 2019. The median age was 63 years (range 36-77) and 43% of patients enrolled (n = 89) were ≥65 years. Among elderly patients, 46 (52%) received FLOT for at least 4 full-dose cycles in the preoperative phase, 82 (92%) underwent surgery, and 56 (62%) started the postoperative phase. The primary end point of the study, pathological complete response (pCR) rate, was similar among patients aged ≥65 and < 65 (6.7% vs 7.7%, respectively). The distribution of pathological stages did not differ according to age (p = 0.473), and disease-free survival (DFS) is unrelated to the age of patients (log-rank 0.57; p = 0.89). The incidence of grade (G) 3-4 adverse events (AEs) was similar in the two age groups (Table) and the 30-day mortality rates after surgery did not differ according to age. Conclusions: FLOT regimen demonstrated to be feasible and safe in elderly patients since no differences were observed in terms of pCR, DFS and safety profile according to age. [Table: see text]

Tumor response score with neoadjuvant FLOT versus FOLFOX in gastric cancer patients: Results from a United States-based cohort.

e16573 Background: A recent RCT comparing FLOT and ECF regimens for locally advanced gastric cancer found FLOT to be superior in pathologic complete response (PCR) rates: 16% versus 6%. We evaluated patients who underwent resection after FLOT and FOLFOX in a diverse US population. Methods: Patients diagnosed with gastric adenocarcinoma at a single institution who underwent preoperative chemotherapy either with FLOT or FOLFOX between 2017 and 2019 were evaluated for pathologic response. Results: Fifty-nine patients underwent gastrectomy for adenocarcinoma. Of these, 59% underwent neoadjuvant chemotherapy: FLOT 20 patients, FOLFOX 12 patients, ECF 1 patient, other regimen 2 patients. Racial/ethnic background of patients were 20% non-Hispanic white, 23% Hispanic/Latino, 40% Asian, 6% black, and 6% other. Three patients (8.6%) had PCR, two received FLOT and one FOLFOX. Four patients had a near complete response (tumor regression score 1), all of whom received FLOT. In total, 16 of 20 patients who received FLOT had at least a partial response whereas only 5 of 12 patients who received FOLFOX had any tumor response (p = 0.027). Among all patients receiving neoadjuvant chemotherapy, 66% had poorly differentiated tumors. Only 1 of these patients experiencing a complete or near complete response compared to 50% of patients with non-poorly differentiated tumors (p = 0.001). Conclusions: In an ethnically diverse US population, tumor regression rates were improved with FLOT when compared to FOLFOX. For medically appropriate patients, strong consideration should be given for FLOT in the neoadjuvant setting.

Trastuzumab with FLOT Regimen for the Perioperative Treatment of Resectable HER2 + Advanced Gastric Cancer: A Retrospective Study.

BackgroundThe aim of this study was to evaluate the efficacy and safety of trastuzumab, combined with the FLOT regimen, in the perioperative treatment of resectable HER-2-positive advanced gastric cancer.MethodsOverall, 45 patients were divided into two groups; 29 patients in the experimental group were treated with trastuzumab combined with FLOT and 16 patients in the control group were treated with FLOT alone. The primary endpoint was objective response rate (ORR), and the secondary endpoints were disease control rate (DCR), tumor regression grade (TRG), surgical margin, side effects, and overall survival.ResultsIn the experimental and control groups, ORR was 72.4% and 43.8% (p=0.226), DCR was 89.7% and 87.5%, R0 resection rate was 96.5% and 93.7%, total/subtotal tumor regression grade was 17.2% and 6.3%, partial tumor regression grade was 27.6% and 18.7% (p=0.468), and 2-year survival rate was 78.1% and 73.9% (p=0.932), respectively. The common side effects were agranulocytosis and vomiting. There was no significant difference between the two groups.ConclusionTrastuzumab combined with FLOT has a good curative effect and safety profile in the perioperative treatment of patients with resectable HER-2-positive advanced gastric cancer. In addition, trastuzumab + FLOT had the same result as FLOT alone, as there was no significant benefit with the addition of T in the group studied.

The potential and challenges of patient-derived organoids in guiding the multimodality treatment of upper gastrointestinal malignancies.

The incidence of adenocarcinoma at the gastrooesophageal junction increased over the last years. Curative treatment for patients with upper gastrointestinal (UGI) malignancies, such as oesophageal and gastric tumours, is challenging and requires a multidisciplinary approach. Radical surgical resection with complete lymphadenectomy is the cornerstone of UGI cancer treatment. Combined with peri-operative treatment (i.e. by applying CROSS, EOX or FLOT regimen), the survival is even better than with surgery alone. However, peri-operative treatment is not effective in all patients, and the most effective strategy is a topic of active debate, as is reflected by varying treatment guidelines between countries. UGI cancers are (epi)genetically highly heterogeneous. It is thus not likely that a uniform treatment will benefit all patients equally well. Over recent years, patient-derived organoids (PDOs) gained more and more interest as an in vitro prediction model that may assist as a diagnostic tool in the future to select and eventually optimize the best peri-operative treatments for each patient. PDOs can be derived from endoscopic tumour biopsies, which maintain heterogeneity in culture. They can be rapidly established and expanded in a relatively short time for in vitro drug screening experiments. This review summarizes the clinical and molecular aspects of oesophageal and gastric tumours, as well as the current progress and remaining challenges in the use of PDOs for drug and radiation screens.

Neoadjuvant chemotherapy for gastric cancer. Frequent overtreatment or meaningful concept?

Neoadjuvant or perioperative therapy with radical surgery is ameaningful approach to improve the prognosis of gastric cancer. The FLOT regimen (5-fluorouracil, leucovorin, oxaliplatin, docetaxel) has been established as a perioperative concept in Germany and is also increasingly being used internationally. The prognostic significance of neoadjuvant chemoradiotherapy has to be awaited based on the results of currently active studies. The microsatellite instability (MSI) status has increasingly gained in importance with respect to decision-making processes in the interdisciplinary tumor board as patients with MSI tumors probably do not benefit from neoadjuvant therapy. Patients with only initial stages of locally advanced MSI tumors (cT2, N0) and those with comorbidities could be spared from neoadjuvant therapy. This article critically deals with the current state of the art concepts as well as with ongoing studies with respect to neoadjuvant and perioperative treatment of gastric cancer. For this purpose, the essential already published and the active studies are presented.

Delayed Posterior Reversible Leukoencephalopathy Syndrome Triggered by FLOT Chemotherapy

Posterior reversible encephalopathy syndrome (PRES) is a potentially severe disorder of the autoregulation of cerebral perfusion. The major clinical manifestations are headache, seizures, altered mental status, and visual loss. The typical radiological finding is vasogenic edema predominating in the white matter of occipital and parietal lobes. PRES is increasingly recognized as a clinico-radiological entity owing to improvements and fast availability of brain imaging, especially magnetic resonance imaging (MRI). We present the exceptional case of a 67-year-old female patient with a gastric adenocarcinoma at stage IIB (T3N0M0) treated by FLOT chemotherapy (5-fluorouracil, oxaliplatin, docetaxel, and folinic acid). Two months after the unique administration of FLOT regimen, she developed sudden posterior headache and visual loss. Blood pressure values were normal. Cerebral tomography showed ischemic-like occipital bilateral lesions, and angiographic sequences revealed breakdown of the blood–brain barrier (BBB). MRI revealed bilateral parieto-occipital T1 hypointensity and T2 hyperintensity, which demonstrated vasogenic edema. The rest of the parts of the lesions were T1 hyperintensity, T2 hyperintensity, and diffusion-weighted imaging (DWI) hyperintensity, which indicate cortical laminar necrosis. After injection of gadolinium, a linear enhancement of the cortex was observed. She was treated with oral nimodipine. Follow-up was characterized by permanent visual sequelae and tetraparesis. PRES represents an urgent neurological condition. Our observation highlights that PRES should be considered in patients under chemotherapy, even when their blood pressure remains within normal range. This is the first report of PRES triggered by FLOT chemotherapy and with a silent window of 2 months between chemotherapy and PRES, widening further the spectrum of chemotherapy-induced PRES. Our case highlights the potential role of FLOT regimen in the pathogenesis of PRES and the need for a novel approach in terms of prevention of this potentially fatal complication when patients receive chemotherapy.

Dose-finding study of modified FLOT (mFLOT) regimen as first-line treatment in Chinese patients with metastatic adenocarcinoma of stomach.

To determine the maximum tolerated dose (MTD) and recommended dose (RD) of modified FLOT regimen (fluorouracil plus leucovorin, oxaliplatin and docetaxel) for treating Chinese patients with metastatic adenocarcinoma of stomach. Chinese patients with untreated advanced or metastatic stomach adenocarcinoma were enrolled. Docetaxel (D), oxaliplatin (O) and leucovorin were administrated intravenously on day 1. Fluorouracil (F) was administrated continuous intravenously on day 1 for 48h. The treatment was repeated every 2weeks. The start doses of docetaxel and oxaliplatin were 40mg/m2 and 65mg/m2, respectively. Dose escalation followed a 3 + 3 design. Total 6 dose levels were set to determine the MTD and RD. Fluorouracil and leucovorin were given as fix doses at 2200mg/m2 and 200mg/m2, respectively. Adverse events that occurred in the first 2 cycles were recorded to determine dose-limiting toxicity (DLT). The primary endpoints were MTD and RD determination. A total of 18 patients were treated in 5 dose levels. DTL occurred in one patient of level 4 (grade 3 hypophosphatemia). Other 3 patients were enrolled in level 4 and no DLTs were observed. In level 5, 2 patients suffered grade 4 neutropenia after first cycle of treatment and were defined as DLTs. Therefore, level 5 (D/O/F: 50/75/2200mg/m2) was defined as MTD and level 4 (D/O/F: 45/75/2200mg/m2) was defined as RD. Common adverse events in first two cycles were nausea, anorexia, leukopenia, neutropenia and anemia. For 16 patients assessable for tumor response, 7 patients had partial response (43.7%) and 5 experienced stable disease. Disease control rate were 75% (12/16). Two patients underwent conversion operation after 6 cycles of treatment. One pathological complete response (case in level 3) and one pathological partial response (case in level 2) were observed. Median progression-free survival was 4.4months (95% CI 2.9-5.9months) in 14 patients. The RD of modified FLOT regimen in Chinese patients with advanced gastric cancer was docetaxel 45mg/m2, oxaliplatin 75mg/m2, leucovorin 200mg/m2 and fluorouracil 2200mg/m2 on day 1 of every 14-day cycle. Its efficacy will be assessed by further phase II study.

Advances in the treatment of gastric cancer: 2019.

The aim of this study was to review studies published within the past year regarding management of gastric cancer. Laparoscopic gastrectomy achieves equivalent survival compared with open gastrectomy in early stage and locally advanced gastric cancer. Adjuvant chemotherapy with 6 months of S-1 and oxaliplatin was superior to 12 months of S-1, and the addition of postoperative radiation therapy did not improve survival. The FLOT regimen is the new standard for preoperative chemotherapy. In metastatic gastric cancer, the addition of docetaxel to S-1 and cisplatin failed to improve overall survival over two-drug chemotherapy. The addition of the immune checkpoint inhibitor pembrolizumab to chemotherapy failed to improve overall survival compared with chemotherapy alone. Laparoscopic gastrectomy is acceptable in early and locally advanced gastric cancer. Combination adjuvant chemotherapy is superior to S-1 monotherapy. Adjuvant radiation therapy after D2 gastrectomy for node-positive gastric cancer does not improve survival. Preoperative chemotherapy with FLOT (5-FU, leucovorin, oxaliplatin and docetaxel) without radiation therapy is the standard treatment in the West. Two-drug chemotherapy is the optimal initial treatment in metastatic disease. Adding pembrolizumab to front-line chemotherapy did not improve survival, with use of immune checkpoint inhibitors reserved to treat chemotherapy refractory metastatic disease.

Systematic review and meta-analysis of docetaxel perioperative chemotherapy regimens in gastric and esophagogastric tumors

FLOT regimen became the standard perioperative treatment in several centers around the world for esophagogastric tumors despite concerns about toxicity. In addition, FLOT has never been compared with other docetaxel-based regimens. To address this question, we conducted a systematic review of PubMed, Embase and Web of Science including prospective or retrospective studies of docetaxel based perioperative regimen in gastric and esophagogastric tumors. Data regarding chemotherapy regimens, efficacy and toxicity were extracted. Outcomes were compared using a random effects model. Of 548 abstracts, 16 were considered eligible. Comparing the studies with meta-analysis we can see that the regimens are similar in terms of pathological complete response, resection rate, progression free survival and overall survival in one year, without significant heterogeneity. The meta-regression of docetaxel dose failed to show any association with dose ranging between 120–450 mg/m². Regarding the toxicity of the regimens it is noted that the regimens are quite toxic (up to 50–70% of grade 3–4 neutropenia). The results of this meta-analysis with a combined sample size of more than 1,000 patients suggest that docetaxel perioperative regimens are equivalent in outcomes. Prospective trials addressing modified regimens should be performed to provide less toxic strategies and be applicable to all patients.

783P - Perioperative chemotherapy with docetaxel, oxaliplatin, fluorouracil and leucovorin (FLOT) versus epirubicin, platinum and capecitabine or flourouracil (EOX/ECF) in resectable gastric or gastroesophageal junction adenocarcinoma: Safety and response data from India

BackgroundGastric and GEJ cancers are one of the top four cancers in India with poor 5-year survival. Post ASCO 2017, we switched to docetaxel-based peri-operative chemotherapy (FLOT) which is the new standard of care. In this audit, we report the pathological response and toxicity of FLOT compared to our older standard (EOX/ECF). MethodsWe analysed our database of 118 patients with gastric or GEJ adenocarcinoma treated at our center from May 2011 to April 2019. 85 patients (72%) received perioperative chemotherapy with three pre-operative and three post-operative 3-week cycles of either EOX (50mg/m2 Epirubicin and 130mg/m2 Oxaliplatin on Day 1 plus 1250mg/m2 Capecitabine for 21 days) or ECF (50mg/m2 Epirubicin and 60mg/m2 Cisplatin on Day 1 plus 800mg/m2/day Fluorouracil as continuous intravenous infusion for 5 days). 33 patients (28%) received four pre-operative and four post-operative 2-week cycles of intravenous FLOT (50mg/m2 Docetaxel, 85mg/m2 Oxaliplatin, 200mg/m2 Leucovorin and 2600mg/m2 Fluorouracil as 24hr infusion on Day 1). We compared the toxicity, and pathological tumor response rates of patients on EOX/ECF and FLOT regimens. ResultsThe patients were aged 30 to 73 years (Median 58 years) and 40 (34%) were women. 85 patients received either EOX/ECF and 33 received FLOT chemotherapy. 64 (75%) patients in EOX/ECF underwent gastrectomy among whom eight (12.5%) had pathological Tumour Regression Score (TRS) of 0 or 1. 24 (72%) patients in FLOT group have undergone gastrectomy of whom six (25%) had TRS of 0 or 1. 34 (40%) patients completed full EOX/ECF regimen while 20 (60%) completed full FLOT. The commonest reason for not completing the peri-operative chemotherapy was toxicity in EOX/ECF group (29%) and refusal to undergo surgery (21%) in the FLOT group. 15% patients did not complete FLOT chemotherapy due to toxicity. ConclusionsFLOT regimen is a better tolerated perioperative therapy in Indian patients achieving higher pathological response compared to EOX/ECF regimen. The patients in both groups are currently on follow up to capture the relapse free survival duration. Legal entity responsible for the studyTanuj Chawla. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

777P - Evaluation of the introduction of primary G-CSF prophylaxis to the FLOT chemotherapy regimen

BackgroundFLOT chemotherapy is a standard of care for patients with early gastric & gastroesophageal junction adenocarcinoma: 4 cycles pre- and 4 post-surgery. It was introduced at the Clatterbridge Cancer Centre in October 2017 following the presentation of FLOT4 trial data. Primary prophylaxis with GCSF was not part of the trial protocol but was allowed as per investigator’s discretion. As such GCSF was not included in the FLOT regimen initially in our centre. However, a significant number of patients could not proceed with their second cycle on time due to prolonged grade 3-4 neutropenia or neutropenic infection. Therefore, primary GCSF prophylaxis was introduced from day 5 of each cycle for 5 days at doses of 300 & 480 micrograms for patients with weight <70 and >70kg, respectively. MethodsPatients were identified from chemotherapy-prescribing records and data was collected from their electronic notes. As a primary objective we compared rates of dose delay because of neutropenia before and after introducing primary GCSF prophylaxis. We also looked at other reasons for dose delay & reduction. Results47 patients started FLOT between October 2017 & July 2018; 41 were men and median age was 63.7 years (36-79). 2 patients had FLOT only in the adjuvant setting. In patients who started neoadjuvant FLOT, 27 patients (57.4%) went on to receive FLOT adjuvantly. 19 patients (40.4%) completed 8 cycles and the median number of cycles received was 5.6 (1-8 cycles). 13 patients had FLOT without primary GCSF prophylaxis, 61.6% of them had dose delays because of neutropenia. After the addition of primary GCSF prophylaxis, the rate of neutropenia resulting in dose delay fell to 2.9% (p=0.00). 46.8% of patients had their treatment delayed for reasons other than neutropenia with the highest rates of deferral seen for non-neutropenic infection (10.6%) and nausea & vomiting (10.6%). 31.9% of patients had their treatment dose reduced; this was most commonly for diarrhoea (10.6%) and peripheral neuropathies (8.5%). Conclusions61.6% of patients receiving the FLOT regimen had treatment delays because of neutropenia. Primary GCSF prophylaxis almost eliminated this problem and reduced the overall rate of dose delays. Therefore, primary GCSF prophylaxis should routinely be used with FLOT. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

An advanced gastric cancer with peritoneal dissemination: complete response achieved with FLOT combination chemotherapy

Introduction: Although chemotherapy is the first recommended treatment of metastatic gastric cancer, a complete response is a rare event.Case: A 56-year-old male was diagnosed as gastric cancer with gastric outlet obstruction, large bowel obstruction and peritoneal dissemination. The patient underwent gastrojejunostomy bypass and ileostomy diversion, and chemotherapy with FLOT (5FU, leucovorin, oxaliplatin, docetaxel) regimen subsequently. After 6 courses of chemotherapy, a computed tomography showed disappearance of gastric mass and disseminated nodules in pelvic cavity, and no visible lesion in gastric mucosa, suggesting a complete clinical response.Conclusion: FLOT regiment in our case succeed to achieve complete clinical response.

Safety and efficacy of a docetaxel-5FU-oxaliplatin regimen with or without trastuzumab in neoadjuvant treatment of localized gastric or gastroesophageal junction cancer: A retrospective study.

BACKGROUNDTriplet chemotherapy, with docetaxel-5FU-oxaliplatin FLOT regimen recently became the standard perioperative treatment for localized gastric cancer (GC). An adapted regimen called TeFOX was recently tested in metastatic setting and gave promising results.AIMTo determine safety and efficacy of TeFOX perioperative regimen.METHODSThis monocentric retrospective study aims to test efficacy and safety of the perioperative TeFOX regimen given alone or in combination with trastuzumab in patients with localized GC. TeFOX consist in docetaxel (50 mg/m²) with oxaliplatin 85 mg/m² and and leucovorin (400 mg/m2) 5 FU bolus (400 mg/m2) on day 1, followed by continuous infusion of 5FU for 46 h (2400 mg/m2) every 2 wk.RESULTSThirty-three consecutive patients were included in this retrospective study. Eighteen patients have a gastroesophageal junction cancer and 11 have a GC. Median follow-up of surviving patients was 32 mo. R0 resection was obtained in 30 (91) patients. Twelve patients (36) had a pathological complete response and 8 (24) patients a nearly complete pathological response. Median OS and PFS were not reached at data base lock. We have observed 6 metastatic relapses and 1 localized relapse. No relapse was observed in patients with pathological complete responses. The most common grade 3-4 adverse events were peripheral neuropathy (21) and asthenia (20).CONCLUSIONTeFOX regimen could be safely administrated in perioperative treatment of localized GC. TeFOX and the FLOT regimen have comparable efficacy and safety profiles.

Perioperative chemotherapy with FLOT vs other regimens for resectable gastric cancer

Perioperative chemotherapy with FLOT vs other regimens for resectable gastric cancer

Docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil (FLOT) as preoperative and postoperative chemotherapy compared with surgery followed by chemotherapy for patients with locally advanced gastric cancer: a propensity score-based analysis.

Introduction: Docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil (FLOT) may improve overall survival (OS) in patients with locally advanced gastric cancer (LAGC); however, evidence for its use as a standard treatment has not been established in China. The aim of this study was to investigate the effectiveness, safety, and feasibility of the FLOT regimen as neoadjuvant chemotherapy in Chinese patients with resectable LAGC.Methods: We conducted an observational study to compare the effectiveness of FLOT regimen consisting of docetaxel (60 mg/m2), oxaliplatin (85 mg/m2), leucovorin (200 mg/m2), and 5-fluorouracil (2,600 mg/m2 as a 24 hr infusion), all given on day 1 and administered every 2 weeks versus initial surgery followed by chemotherapy in patients with clinical T3–4 LAGC. OS was compared by using the Cox proportional hazards regression model and the Kaplan–Meier curve adjusted by inverse probability of treatment weighting (IPTW) and propensity score-matched (PSM) analysis. In addition, we performed subgroup analyses to determine the effectiveness of the FLOT regimen in clinically relevant patient subsets.Results: Overall, 47 patients who received initial FLOT chemotherapy and 269 patients who received initial surgery were enrolled in this study. In the PSM analysis, the FLOT-first group showed favorable OS compared with the surgery-first group (41 vs 41 [HR, 0.416; 95% CI, 0.218–0.794; P=0.008]), and 3-year survival rates were 58.7% and 30.9% in the FLOT-first group and surgery-first group, respectively. IPTW analysis showed similar results. However, the effect of FLOT was low (HR, 0.868; 95 CI%, 0.215–3.504) in patients without lymph node metastasis.Conclusion: Our study suggests that preoperative FLOT chemotherapy is safe and feasible. In terms of OS, FLOT may be superior to initial surgery followed by chemotherapy in reducing morbidity with resectable LAGC.

Perioperative Treatment in Gastric Cancer—Developments in Patient Selection

Gastric cancer (GC) is a major public health issue. It is considered the 5th most common cancer diagnosed worldwide and it is one of the main causes of malignant disease-associated morbidity and mortality. The cornerstone of curative treatment is still surgery, and since the rate of relapse is high, a multidisciplinary approach is warranted in most developed countries. And while there have been recent developments in the perioperative scenario namely the FLOT regimen, little has advanced considering patient selection. We have reviewed the major trials in this setting and provide some insights from recently reported microsatellite instability (MSI) in a subgroup analysis in the MAGIC trial patients that seem to suggest an opportunity to patient selection. Furthermore, GC subtyping may prove helpful selecting candidates to immunotherapy or even multimodal therapy in the future. As the paradigm is moving towards a precision oncology model, GC patient selection remains one the biggest challenges in oncology but seems closer to clinical practice reality as new developments are being reported.

The postoperative part of perioperative chemotherapy fails to provide a survival benefit in completely resected esophagogastric adenocarcinoma

BackgroundBased on two benchmark studies perioperative chemotherapy (CTx) has become standard treatment for locally advanced esophagogastric adenocarcinoma (EGA) in Europe. However, only half of the patients in both studies actually received postoperative CTx (aCTx). Thus, we evaluated the prognostic impact of preoperative CTx (nCTx) and aCTx combined versus nCTx alone. Furthermore, we aimed to identify subgroups potentially beneficial of aCTx and factors associated with its non-administration. MethodsWe retrospectively analyzed 299 consecutive patients with EGA, who underwent complete resection (all M0, R0) after nCTx in our institution and were eligible for aCTx. Patients with and without aCTx were compared regarding clinicopathological data, treatment, morbidity, and long-term prognosis. Results129 patients (43.1%) did not receive aCTx. Administration of aCTx did not significantly improve overall (OS) and recurrence free survival (RFS) (median OS: 78.2 months vs. not reached, p = 0.331; RFS: 43.3 vs. 41.1 months, p = 0.118), but was an independent positive predictor of RFS (HR 1.6 95%CI 1.1–2.5, p = 0.024). aCTx improved RFS in non-intestinal tumors (p = 0.023) and patients receiving FLOT regimen (p = 0.038). By logistic regression analysis factors predictive of non-administration of aCTx were older age (>65 years: OR 3.2, p = 0.028), longer hospital stay (15–28 days: OR 2.6, p = 0.001; >28 days: OR 5.2, p < 0.001), and histopathologic non-response (OR 1.9, p = 0.023). ConclusionAdvanced age, histopathologic non-response, and prolonged convalescence due to postoperative morbidity lead to omission of aCTx. However, this study could not provide evidence to support the beneficial role of aCTx in perioperative chemotherapy regimens for a selected patient collective with EGA and excellent prognosis.

Interim safety analysis of a phase III trial with 5-FU, oxaliplatin, and docetaxel (FLOT) versus epirubicin, cisplatin, and 5-FU (ECF) in patients with locally advanced, resectable gastric/oesophagogastric junction (OGJ) cancer: The AIO-sto-0210 FLOT4 study.

4079 Background: Perioperative ECF is a standard treatment for localized gastric/OGJ adenocarcinoma. However, 5-year survival rate remains below 40%. The FLOT regimen is an effective combination with pathologic response rates in the 15% range. This phase III study compares both regimens in resectable stages. Methods: Pts are stratified by different baseline criteria and randomized to either 3 + 3 perioperative cycles of ECF (epirubicin 50 mg/m2, d1; cisplatin 60 mg/m², d1; 5-FU 200 mg/m², d1-d21, qd21) or 4 + 4 cycles of perioperative FLOT (docetaxel 50mg/m2, d1; 5-FU 2600 mg/m², d1; leucovorin 200 mg/m², d1; oxaliplatin 85 mg/m², d1, qd14). 5-FU can be replaced by capecitabine in the ECF-arm (ECX). Central pathology is performed. This is a preplanned safety analysis after 300 patients. Results: The ongoing studyhas enrolled 380 of planned 590 pts, so far. 305 pts were included in this analysis. Median age is 62 yrs; 78% of pts are male. The primaries were gastric in 44.9%, OGJ in 50.4% and not evaluable/documented in 4.7% of pts. 281 pts were eligible for safety analyses. Median no. of preoperative cycles was 3 and 4 with ECF/ECX and FLOT, respectively, 35.9% vs. 44.6% of pts (ECF/ECX vs. FLOT) started postoperative chemotherapy (ct) and 22.5% vs 33.1% received all planned cycles. Grade 3/4 neutropenia was observed in 28.0% of ECF/ECX and 45.3% of FLOT pts (p=.0026). Thromboembolic events occurred in 14.1% vs. 5.8% in pts with ECF/ECX vs. FLOT (p=.027). Serious adverse events occurred in 52.1% vs. 47.5% of pts with ECF/ECX vs. FLOT (p=.48). Preoperative delay/interruptions of ct were observed in 71.1% vs. 56.8% of pts with ECF/ECX vs. FLOT (p=.013). Dose modifications of preoperative ct were performed in 27.5% vs. 20.1% of treatment cycles with ECF/ECX vs. FLOT, respectively. 197 pts have undergone surgery so far. Severe surgical morbidity was similar in both arms (ECF/ECX, 19.8%; FLOT, 16.8%). Surgical mortality was observed in 4 and 2 pts with ECF/ECX and FLOT. Toxic deaths were observed in 1 pt each. Conclusions: Perioperative FLOT is feasible and safe. Clinical trial information: NCT01216644.

The safety and efficacy of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) combination in the front-line treatment for patients with advanced gastric or gastroesophageal adenocarcinoma: phase II trial

Combination therapy with docetaxel, cisplatin, and 5-FU has been shown to increase time to progression (TTP) and overall survival (OS) for patients with advanced gastric cancer; this regimen is limited by significant toxicity, including complicated neutropenia. This study was designed to incorporate docetaxel into a tolerable biweekly (once every 2 weeks) oxaliplatin-based chemotherapy regimen. Patients with measurable advanced and metastatic gastric or gastroesophageal cancer, aged >18 years, and with ECOG two or less, received oxaliplatin 85 mg/m(2), docetaxel 50 mg/m(2) on day 1, leucovorin 200 mg/m(2) on days 1 and 2, and 5-FU 1,200 mg/m(2) 24-h infusion on days 1 and 2 of every 2-week cycle. Toxic effects were graded according to NCI-CTC version 3. Responses were classified according to World Health Organization criteria. Fifty patients were included, 47 assessed for efficacy and toxicity. Median age was 55 years. The majority had metastatic disease (72 %). The over all response was observed in 55.3 % patients. Median TTP and OS were 6 and 10 months, respectively. Grade 3 or 4 hematological toxic effects were included neutropenia, leukopenia, and thrombocytopenia observed in 21 (44.7 %), 12 (25.5 %), and 1 (2.1 %) patients, respectively. Non-hematological were diarrhea (14.9 %), fatigue (12.7 %), and peripheral neuropathy (8.5 %). Complicated neutropenia (febrile neutropenia associated with infection) was observed in one (2.1 %) patient only. Biweekly FLOT regimen has tolerable toxicity, and efficacy in line with that of DCF protocol. The FLOT regimen needs more evaluation to be considered as alternative to DCF.

Feasibility of perioperative chemotherapy with infusional 5-FU, leucovorin, and oxaliplatin with or without docetaxel, in elderly patients with locally advanced esophagogastric cancer.

4080 Background: The aim of this study was to determine feasibility and efficacy of perioperative chemotherapy in elderly, potentially operable esophagogastric cancer patients. Methods: Patients aged 65 or older with locally advanced esophagogastric adenocarcinoma were randomized to perioperative chemotherapy consisting of four preoperative and four postoperative cycles of infusional 5-FU, leucovorin, and oxaliplatin (FLO) with or without docetaxel 50mg/m² (FLOT), every 2 weeks. Results: 44 patients with a median age of 70 years were randomized to either FLO (22) or FLOT (22) chemotherapy. In the FLO and FLOT group, 20 and 18 patients completed four cycles of preoperative chemotherapy and 17(77.3%) and 15(68.2%) patients proceeded to surgery, with 88.2% and 93.3% R0 resections, respectively. FLOT was associated with significantly more treatment-related NCI-CTC grade 3/4 adverse events, including neutropenia (p&lt;.0001), leukopenia (p&lt;.0001), stomatitis (p=0.02) and nausea (p=0.02) and a higher rate of patients experiencing a ≥10-points deterioration of EORTC QoL global health status scores (FLOT, 54%; FLO 23.1%) at 8 weeks. No perioperative mortality was observed, however postoperative morbidity was nearly doubled with the FLOT regimen (60% versus 35.3% for FLO), mostly due to wound infections in the FLOT group (20%). 11 (64.7%) and 9 (60.0%) of patients in the FLO/FLOT group were able to undergo postoperative chemotherapy. Compared with the FLO group, the FLOT group had a better response rate (61.9% vs. 18.2%) and a trend towards an improved median disease free survival (21.1 vs. 12.0 months; p=0.09). Conclusions: Age alone is not a contra-indication for the selection of patients for three-drug regimens in the multimodal treatment approach. FLOT seems to be more effective than FLO, but is associated with an increased toxicity and higher postoperative morbidity. Therefore, careful patient selection is warranted.