This phase II trial evaluated the efficacy of cisplatin and fluorouracil (CF)-based combination neoadjuvant chemotherapy on the outcome of patients with resectable locally advanced esophageal ...squamous cell carcinoma (ESCC). We compared the recurrence-free survival (RFS) associated with CF plus Adriamycin (ACF) with that associated with CF plus docetaxel (DCF) to select an alternative regimen in a new phase III trial investigating the optimal neoadjuvant treatment of patients with ESCC.
Patients with resectable advanced ESCC were randomly assigned to either ACF (Adriamycin 35mg/m2, cisplatin 70mg/m2 i.v. on day 1, fluorouracil 700mg/m2 continuous infusion for 7 days) every 4 weeks or DCF (docetaxel 70mg/m2, cisplatin 70mg/m2 i.v. on day 1, fluorouracil 700mg/m2 continuous infusion for 5 days) every 3 weeks. Surgery was scheduled after completion of two cycles of chemotherapy. The primary end point was RFS, analyzed by the intention-to-treat.
Between October 2011 and October 2013, 162 patients at 10 institutions were enrolled in the study, all of whom were eligible and randomly assigned to the two groups (81 to the ACF group and 81 to the DCF group). The R0 resection rates for the ACF and DCF groups were equivalent (95.9% versus 96.2%, P=0.93). The 2-year RFS and overall survival rates for DCF versus ACF were 64.1% versus 42.9% (hazard ratio 0.53, 95% confidence interval 0.33–0.83, P=0.0057) and 78.6% versus 65.4% (P=0.08), respectively.
Compared with ACF, DCF chemotherapy was associated with prolonged RFS for patients with resectable advanced ESCC. Thus, DCF chemotherapy has potential as a standard neoadjuvant therapy for resectable ESCC.
University Hospital Medical Information Network Clinical Trials Registry of Japan (identification number UMIN000004555/000004616).
Neoadjuvant chemotherapy (NAC) is a promising method of improving the survival of resectable gastric cancer. Cisplatin/S-1 (CS) and docetaxel/cisplatin/S-1 (DCS) are both effective against metastatic ...gastric cancer. This report clarified the impact of these regimens on early endpoints, including the pathological responses, chemotherapy-related toxicities, and surgical results.
Patients with M0 and either T4 or T3 in case of junctional cancer or scirrhous type received two or four courses of cisplatin (60 mg/m2 at day 8)/S-1 (80 mg/m2 for 21 days with 1 week rest) or docetaxel (40 mg/m2 at day 1)/cisplatin (60 mg/m2 at day 1)/S-1 (80 mg/m2 for 14 days with 2 weeks rest) as NAC. Patients then underwent D2 gastrectomy and adjuvant S-1 chemotherapy for 1 year. The primary endpoint was the 3-year overall survival.
Between October 2011 and September 2014, 132 patients were assigned to receive CS (n = 66; 33 in 2 courses and 33 in 4 courses) or DCS (n = 66; 33 in 2 courses and 33 in 4 courses). The respective major grade 3 or 4 hematological toxicities (CS/DCS) were leukocytopenia (14.1%/26.2%), neutropenia (29.7%/47.7%), anemia (14.1%/12.3%), and platelet reduction (3.1%/1.5%). The rate of pathological response, defined as a complete response or < 10% residual cancer remaining, was 19.4% in the CS group and 15.4% in the DCS group, and 15.6% in the two-course group and 19.0% in the 4-course group. The R0 resection rate was 72.7% in the CS group and 81.8% in the DCS group and 80.3% in the two-course group and the 74.2% in the four-course group. No treatment-related deaths were observed.
Our results do not support three-drug therapy with a taxane over two-drug therapy, or any further treatment beyond two cycles as an attractive candidate for the test arm of NAC.
Background
The appropriate surgical procedure for patients with upper third early gastric cancer is controversial. We compared total gastrectomy (TG) with proximal gastrectomy (PG) in this patient ...population.
Methods
A multicenter, non-randomized trial was conducted, with patients treated with PG or TG. We compared short- and long-term outcomes between these procedures.
Results
Between 2009 and 2014, we enrolled 254 patients from 22 institutions; data from 252 were included in the analysis. These 252 patients were assigned to either the PG (
n
= 159) or TG (
n
= 93) group. Percentage of body weight loss (%BWL) at 1 year after surgery, i.e., the primary endpoint, in the PG group was significantly less than that of the TG group (− 12.8% versus − 16.9%;
p
= 0.0001). For short-term outcomes, operation time was significantly shorter for PG than TG (252 min versus 303 min;
p
< 0.0001), but there were no group-dependent differences in blood loss and postoperative complications. For long-term outcomes, incidence of reflux esophagitis in the PG group was significantly higher than that of the TG group (14.5% versus 5.4%;
p
= 0.02), while there were no differences in the incidence of anastomotic stenosis between the two (5.7% versus 5.4%;
p
= 0.92). Overall patient survival rates were similar between the two groups (3-year survival rates: 96% versus 92% in the PG and TG groups, respectively;
p
= 0.49).
Conclusions
Patients who underwent PG were better able to control weight loss without worsening the prognosis, relative to those in the TG group. Optimization of a reconstruction method to reduce reflux in PG patients will be important.
Background
Total gastrectomy for gastric cancer is associated with excessive weight loss and decreased calorie intake. Nutritional support using eicosapentaenoic acid modulates immune function and ...limits catabolism in patients with advanced cancer, but its impact in the perioperative period is unclear.
Methods
This was a randomized phase III clinical trial of addition of eicosapentaenoic acid‐rich nutrition to a standard diet in patients having total gastrectomy for gastric cancer. Patients were randomized to either a standard diet or standard diet with oral supplementation of an eicosapentaenoic acid (ProSure®), comprising 600 kcal with 2·2 g eicosapentaenoic acid, for 7 days before and 21 days after surgery. The primary endpoint was percentage bodyweight loss at 1 and 3 months after surgery.
Results
Of 127 eligible patients, 126 were randomized; 124 patients (61 standard diet, 63 supplemented diet) were analysed for safety and 123 (60 standard diet, 63 supplemented diet) for efficacy. Across both groups, all but three patients underwent total gastrectomy with Roux‐en‐Y reconstruction. Background factors were well balanced between the groups. Median compliance with the supplement in the immunonutrition group was 100 per cent before and 54 per cent after surgery. The surgical morbidity rate was 13 per cent in patients who received a standard diet and 14 per cent among those with a supplemented diet. Median bodyweight loss at 1 month after gastrectomy was 8·7 per cent without dietary supplementation and 8·5 per cent with eicosapentaenoic acid enrichment (P = 0·818, adjusted P = 1·000). Similarly, there was no difference between groups in percentage bodyweight loss at 3 months (P = 0·529, adjusted P = 1·000).
Conclusion
Immunonutrition based on an eicosapentaenoic acid‐enriched oral diet did not reduce bodyweight loss after total gastrectomy for gastric cancer compared with a standard diet. Registration number: UMIN000006380 (
http://www.umin.ac.jp/)
Immunonutrition of no benefit
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