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

ABSTRACT: The aim of this exploratory subgroup analysis of the fluorouracil, oxaliplatin, docetaxel (FLOT)65+ trial was to determine tolerability and feasibility of perioperative chemotherapy in elderly, potentially operable esophagogastric cancer patients.Patients aged ≥65 with locally advanced esophagogastric adenocarcinoma were randomized to perioperative chemotherapy consisting of four pre- and four postoperative cycles of infusional 5-FU, leucovorin, and oxaliplatin (FLO) without or with docetaxel 50 mg m(-)(2) (FLOT), every 2 weeks.Forty-four patients with a median age of 70 years were randomized and 43 patients started preoperative chemotherapy (FLO, 22; FLOT, 21). Thirty-eight (86.4%) patients completed four cycles of preoperative chemotherapy and 32 (74.4%) proceeded to surgery, with 67.4% R0 resections on intent-to-treat analysis (90.1% of the 32 patients who underwent resection). Median overall survival was not reached and median progression-free survival (PFS) was 17.3 months. Compared with the FLO group, the FLOT group showed a trend towards an improved median PFS (21.1 vs 12.0 months; P=0.09), however, associated with increased chemotherapy related toxicity. No perioperative mortality was observed. Postoperative morbidity was observed in 46.9% of patients (FLO, 35.3%; FLOT, 60%).Neoadjuvant FLO or FLOT may offer a reasonable chance of curative surgery in elderly patients with locally advanced resectable gastroesophageal cancer. However, the increase in side effects with the FLOT regimen and postoperative morbidity should be carefully considered when an intensive chemotherapy regimen is planned.

SUBMITTER: Lorenzen S

PROVIDER: S-EPMC3593547 | biostudies-other | 2013 Feb

REPOSITORIES: biostudies-other

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Project description:ImportancePerioperative chemotherapy is a potential treatment for locally advanced gastric cancer. However, the optimal chemotherapy regimen remains unknown.ObjectiveTo investigate the safety and efficacy of S-1 plus oxaliplatin (SOX) vs fluorouracil, leucovorin, and oxaliplatin (FOLFOX) as a perioperative chemotherapy regimen for patients with locally advanced gastric cancer.Design, setting, and participantsIn this phase 3, open-label, multicenter, randomized clinical trial, patients from 12 Chinese hospitals were enrolled between June 2011 and August 2016, with a last follow-up date of September 2019. The primary tumor was evaluated as either invading the serosa or the adjacent structures with or without metastatic lymph nodes, and with no evidence of distant metastases. Data were analyzed from December 2019 to June 2020.InterventionsPatients were randomly assigned (1:1) to receive either 6 perioperative (2-4 preoperative and 2-4 postoperative) 3-week cycles of 130 mg/m2 oxaliplatin on day 1 and 80 to 120 mg/d S-1 orally daily for 2 weeks (SOX) or 130 mg/m2 oxaliplatin, 400 mg/m2 fluorouracil, 400 mg/m2 leucovorin, and 2400 mg/m2 fluorouracil as 46-hour infusion on day 1 (FOLFOX).Main outcomes and measuresThe primary end point was 3-year overall survival (OS). An absolute noninferiority margin of -8% was chosen.ResultsA total of 583 patients were enrolled; 293 were randomized to the SOX group and 290 were randomized to the FOLFOX group. Twelve patients (2.1%) refused preoperative chemotherapy (5 patients in the SOX group and 7 patients in the FOLFOX group), leaving a total of 288 patients in the SOX group (median [range] age, 61 [24 to 78] years; 197 men [68.4%]) and 283 patients in the FOLFOX group (median [range] age, 62 [24 to 80] years; 209 men [73.9%]) who received preoperative chemotherapy. The 3-year OS rate was 75.2% (95% CI, 70.3% to 80.5%) in the SOX group and 67.8% (95% CI, 62.5% to 73.5%) in the FOLFOX group. The absolute difference of 3-year OS rate between the 2 groups was 7.4% (95% CI, -0.1% to 14.9%), which was greater than the prespecified noninferiority margin (-8%) and showed the noninferiority of perioperative chemotherapy with SOX compared with FOLFOX.Conclusions and relevanceIn this randomized clinical trial, SOX was noninferior to FOLFOX as perioperative chemotherapy for patients with locally advanced gastric cancer and could be recommended as an alternative treatment for these patients in Asia.Trial registrationClinicalTrials.gov Identifier: NCT01364376.

Project description:BackgroundPerioperative chemotherapy and surgery are a standard of care for patients with resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma. However, the prognosis remains poor for this population. The FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) regimen is considered as the new standard chemotherapy regimen for perioperative strategy, despite associated with a 5-year overall survival rate (OS) amounting 45% following radical surgery. Immunotherapy with antibodies that inhibit PD-1/ PD-L1 interaction has recently emerged as a new treatment option with promising and encouraging early trial results for patients with advanced or metastatic gastric or GEJ adenocarcinoma. Currently, no trials have investigated the impact of perioperative immunotherapy in combination with chemotherapy for resectable gastric or GEJ adenocarcinoma.MethodsGASPAR trial is a multicenter open-label, nonrandomized, phase II trial to evaluate the efficacy and safety of Spartalizumab in combination with the FLOT regimen as perioperative treatment for resectable gastric or GEJ adenocarcinoma. The main endpoint is the proportion of patients with pathological complete regression (pCR) in the primary tumour after preoperative treatment. Systemic treatment will include a pre-operative neoadjuvant and a post-operative adjuvant treatment, during which FLOT regimen will be administered every two weeks for 4 cycles and Spartalizumab every four weeks for 2 cycles. For patients with confirmed tumor resectability on imaging assessment, surgery will be realized within 4-6 weeks after the last dose of preoperative chemotherapy. Post-operative systemic treatment will then be initiated within 4-10 weeks after surgery. Using a Simon's two-stage design, up to 67 patients will be enrolled, including 23 in the first stage.DiscussionCurrently, no trials have investigated the impact of immunotherapy in combination with FLOT chemotherapy as perioperative treatment for resectable gastric or GEJ adenocarcinoma. Some studies have suggested a change in the tumor immune micro-environment following neoadjuvant chemotherapy in this setting, reinforcing the relevance to propose a phase II trial evaluating efficacy and safety of Spartalizumab in combination with perioperative chemotherapy, with the aim of improving treatment efficacy and survival outcomes.Trial registrationNCT04736485, registered February, 3, 2021.

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

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