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

Background: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.Methods: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.Results: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%).Conclusion: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.

Efficacy of preoperative chemotherapy regimens in patients with initially unresectable locally advanced gastric adenocarcinoma: Capecitabine and oxaliplatin (XELOX) or with epirubicin (EOX).

“…We confirmed that even additional epirubicin was added, EOX regimen could not show more advantages compared to XELOX regimen in aspects of response rate, conversion rate from unresectable to resectable and survival. The result was similar with other studies in assessing difference between two-drug and threedrug regimens as preoperative or first-line chemotherapy treatment [16,17]. Lorenzen S demonstrated [16] that neoadjuvant FLOT (infusional 5-FU, leucovorin, oxaliplatin and docetaxel) offered an acceptable chance of curative surgery compared with FLO (infusional 5-FU, leucovorin, and oxaliplatin) in elderly patients with locally advanced gastroesophageal cancer, while a French Intergroup Study [17] even showed that doublet FOLFIRI (Fluorouracil, Leucovorin, and Irinotecan) as first-line treatment for advanced gastric cancer had significantly better TTF (Time to failure) than triplet ECX (Epirubicin, Cisplatin and Capecitabine) .…”

The Italian Research Group for Gastric Cancer (GIRCG) guidelines for gastric cancer staging and treatment: 2015

“…The randomized studies MAGIC [9] and FNCLCC [10] [11][12][13]. At present, there are doubts about the response rate of signet-ring cell tumors to neoadjuvant treatment, because of a presumed intrinsic chemoresistance of these cancers.…”

Curcumin Induces Apoptosis in SGC-7901 Gastric Adenocarcinoma Cells via Regulation of Mitochondrial Signaling Pathways

“…Currently, platinum, 5-fuorouracil (5-FU), and taxanes are recommended as the first-line chemotherapy for the treatment of gastric cancer (Chen et al, 2013). However, the response rate of drug chemotherapy remains lower than 20% and the chemotherapeutics sometimes lead to severe toxicity at their therapeutic dose (Lorenzen et al, 2013). Therefore, to discover the effective and novel chemotherapy is requisite.…”