Abstract
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.
Highlights
FLOT regimen became the standard perioperative treatment in several centers around the world for esophagogastric tumors despite concerns about toxicity
A phase 3 randomized trial showed improved overall survival among patients with operable gastric cancer treated with perioperative chemotherapy based on docetaxel, oxaliplatin and 5FU (FLOT) over epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX)[5,6]
Regarding the toxicity of the regimens, we found that docetaxel based perioperative regimens are quite toxic, the FLOT combination had higher levels of neurosensory toxicity and mucositis grade 3 and 4 compared with other regimens, the DCF modifications with infusional fluorouracil seems to be better tolerated than the regimens with oral fluoropyrimidines mainly to hematological toxicity, others differences presumably are intensified by the use of colony stimulating factors only in character of secondary prophylaxis Table 2, Appendix 1
Summary
FLOT regimen became the standard perioperative treatment in several centers around the world for esophagogastric tumors despite concerns about toxicity. 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. A phase 3 randomized trial showed improved overall survival among patients with operable gastric cancer treated with perioperative chemotherapy based on docetaxel, oxaliplatin and 5FU (FLOT) over epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX)[5,6]. Other docetaxel-based regimens in the perioperative setting have been previously studied and apparently, they present similar results to the FLOT regimen with different toxicity profiles, direct comparisons between these different regimens have not been performed[9,10,11]
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