The evidence supporting this protocol is supported by ESPAC-4,a phase III, multi-centre, international, open-label randomised controlled trial comparing gemcitabine and capecitabine (GEM-CAP) versus gemcitabine alone (GEM), in patients with resected pancreatic ductal adenocarcinoma.r
Between November 2008 and September 2014, 732 patients were enrolled into the study. The median age was 65 years and 57% of patients were male. 97% of patients had a WHO performance status of 0 or 1. Median maximum tumour size was 30 mm, 60% were R1 resections, 80% were node positive, and 39% were poorly differentiated. 730 evaluable patients were randomised within 12 weeks of surgery to receive either adjuvant chemotherapy with IV gemcitabine (1000 mg/m2) as monotherapy on days 1, 8, and 15 every 28 days for 6 cycles (n = 366), or adjuvant chemotherapy with IV gemcitabine (1000 mg/m2) on days 1, 8, and 15 in combination with capecitabine 1660 mg/m2/day (in two divided doses) administered orally for 21 days followed by 7 days rest, repeated every 28 days for a total of 6 cycles (n = 364).r
The primary end point was overall survival. Secondary end points were relapse free survival, 2 and 5 year survival rates, lymph node spread, distant metastases or death from any cause. Toxicity and quality of life was also assessed.
In December 2015, the Independent Trial Steering committee requested that the trial proceed to full analysis.
After a median follow up time of 43.2 months (range 39.7 - 45.5 months), the median overall survival for patients in the gemcitabine plus capecitabine group was 28.0 months (95% CI 23.5 - 31.5) compared with 25.5 months (22.7 - 27.9) in the gemcitabine group (HR 0.82, 95% 0.68 -0.98, p=0.032). The median relapse-free survival was 13.9 months (12.1 – 16.6) in the gemcitabine and capecitabine group and 13.1 months (11.6 – 15.3) in the gemcitabine group (HR 0.86, 95% CI 0.73-1.02, p=0.082). The estimated 5 year survival was 28.8% (22.9 – 35.2) for the gemcitabine plus capecitabine group and 16.3% (10.2 – 23.7) for the gemcitabine group. Gemcitabine plus capecitabine favoured survival in most clinical subgroups.r
There was no significant effect in the longitudinal estimate of quality of life between the treatment groups.
Kaplan Meier plots for overall survival (A) and for overall survival by resection margin status and treatment group (B)r
© Lancet 2017
All six cycles of treatment were completed by 54% of patients in the gemcitabine plus capecitabine group and 65% of patients in the gemcitabine group. 1 There were 608 grade 3–4 events reported by 226 of 359 patients in the gemcitabine plus capecitabine group and 481 grade 3-4 events reported by 196 of 366 patients in the gemcitabine group. Grade 3-4 neutropenia, diarrhoea and hand-food syndrome was more common in the gemcitabine plus capecitabine group.r
© Lancet 2017