Comparison of efficacy and safety of first-line palliative chemotherapy with EOX and mDCF regimens in patients with locally advanced inoperable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma: a randomized phase 3 trial

Abstract

The aim of the study was to compare efficacy and safety of first-line palliative chemotherapy with (EOX) epirubicin/oxaliplatin/capecitabine and (mDCF) docetaxel/cisplatin/5FU/leucovorin regimens for untreated advanced HER2-negative gastric or gastroesophageal junction adenocarcinoma. Fifty-six patients were randomly assigned to mDCF (docetaxel 40 mg/m2 day 1, leucovorin 400 mg/m2 day 1, 5FU 400 mg/m2 bolus day 1, 5FU 1000 mg/m2/d days 1 and 2, cisplatin 40 mg/m2 day 3) or EOX (epirubicin 50 mg/m2 day 1, oxaliplatin 130 mg/m2 day 1, capecitabine 1250 mg/m2/d days 1–21). The primary endpoint was overall survival. The median overall survival was 9.5 months with EOX and 11.9 months with mDCF (p = 0.135), while median progression-free survival was 6.4 and 6.8 months, respectively (p = 0.440). Two-year survival rate was 22.2 % with mDCF compared to 5.2 % with EOX. Patients in the EOX arm had more frequent reductions in chemotherapy doses (34.5 vs. 3.7 %; p = 0.010) and delays in subsequent chemotherapy cycles (82.8 vs. 63.0 %; p = 0.171). There was no statistically significant difference in the rates of grade 3–4 adverse events (EOX 79.3 vs. mDCF 61.5 %; p = 0.234). As compared with the mDCF, the EOX regimen was associated with more frequent nausea (34.5 vs. 15.4 %), thromboembolic events (13.8 vs. 7.7 %), abdominal pain (13.8 vs. 7.7 %) and grades 3–4 neutropenia (72.4 vs. 50.0 %), but lower incidences of anemia (44.8 vs. 61.5 %), mucositis (6.9 vs. 15.4 %) and peripheral neuropathy (6.9 vs. 15.4 %). In conclusion, the mDCF regimen was associated with a statistically nonsignificant 2.4-month longer median overall survival without an increase in toxicity. This trial is registered at ClinicalTrials.gov, number NCT02445209.

Anthracycline-based triplets do not improve the efficacy of platinum-fluoropyrimidine doublets in first-line treatment of advanced gastric cancer: real-world data from the AGAMEMON National Cancer Registry

“…The role of adding anthracyclines to platinum and fluoropyrimidine-based schedules is even more controversial if we consider that docetaxel-containing triplets have demonstrated their superiority to doublets not containing docetaxel in a multicenter, phase III study [25] and have achieved an increase in responses and a trend toward greater survival rates in a meta-analysis that included 12 RCTs [26]. Likewise, triplets with docetaxel have displayed a trend toward superiority over triplets with anthracyclines (NCT02445209) [27]. The conclusions of our study also differ to a certain extent from an earlier analysis presented by our own group, in which greater OS was observed in favor of the use of three-drug vs. two-drug schedules in general: HR, 0.77; 95% CI, 0.65-0.92; stratified log-rank test, p = 0.004.…”

“…While these circumstances are obviously conceivable, it is possible that the best choice in cases such as these might be a triplet containing docetaxel and not necessarily epirubicin [25][26][27].…”

TOXview: a novel graphical presentation of cancer treatment toxicity profiles

“…To counter this problem, we used a prespecified set of common AEs of chemotherapy; as such the most important AEs could be compared between the regimens. In addition, very few studies explicitly mention that the adverse events are possibly related to treatment, which could also result in underreported adverse events [41,64]. For future research, using individual patient data or creating an international adverse event report system e.g.…”

The Efficacy and Safety of Modified Docetaxel, Cisplatin, and 5-Fluorouracil Vs. Epirubicin, Oxaliplatin, and Capecitabine Regimen in the Advanced Gastric Cancer: A Randomized Controlled Clinical Trial

“…Many researchers have used this regimen, alone or in combination with other chemotherapy agents, to treat advanced gastric cancer and confirmed its safety and efficacy (Unek et al, 2013). Despite the acceptable level of toxicity associated with this regimen, there are still uncertainties about its application, which indicate the need for future studies to evaluate different doses of DCF (de Gramont et al, 1997;Cunningham et al, 2008;Shah et al, 2010;Unek et al, 2013;Kalinka-Warzocha et al, 2015;Ochenduszko et al, 2015) Another regimen used in some oncologic centers as first-line treatment for gastric and gastroesophageal junction cancers is epirubicin, oxaliplatin, and capecitabine (EOX) regimen, which showed a significantly higher efficacy in REAL2 clinical trial, compared with the ECF regimen. In this trial, the survival rate was 11.2 months in EOX patients versus 9.9 months in ECF patients.…”