LBA4006 Background: The effect of adjuvant treatment on overall survival (OS) of resected ampullary adenocarcinoma is not known. The aim was to compare the survival effect of adjuvant chemotherapy compared to observation (OBS) after resection and within the chemotherapy group to compare 5-fluorouracil/folinic acid (5-FU/FA) against gemcitabine (GEM).
METHODS
Patients were stratified by R0/R1 margins, randomised into three arms: (1) 5-FU/FA (FA, 20 mg/m2 iv bolus then 5-FU, 425 mg/m2, iv bolus, 1-5d every 28 days); (2) GEM (100mg/m2 iv infusion 1d, 8d and 15d every 4 weeks); (3) observation. The primary outcome measure was OS of chemotherapy versus no chemotherapy. 300 patients (200 chemotherapy and 100 observation) would provide 80% power to detect a 15% 5y survival difference, p<0.05.
RESULTS
304 patients were randomised (July 2000 to April 2008), 199 to chemotherapy (101 5FU, 98 GEM) and 105 to observation. Median (range) age was 62 (35 - 81) years; 187 (61.5%) were men. Median (IQR) maximum tumour diameter was 20.0 (15.0 - 28.0) mm, 186 (63%) were moderately differentiated tumours, 174 (57%) had involved lymph nodes and 276 (91%) were R0 resections. Independent prognostic factors were tumour diameter and grade, lymph node status and R0/R1 status. Median (95% CI) OS for chemotherapy [57.1 (41.7 - 73.8) months] versus no chemotherapy [43.0 (27.6 - ) months] gave an HR (95% CI) of 0.85 (0.61 - 1.18), p=0.323. For R0 patients median (95% CI) OS for chemotherapy [58.4 (45.4 - 84.0) months] versus no chemotherapy [45.1 (26.7 - ) months] gave an HR (95% CI) of 0.78 (0.55 - 1.11), p=0.173. Cox proportional hazards modelling for all 304 patients p=0.161 and for 276 R0 patients p=0.057.
CONCLUSIONS
This is the only large adjuvant trial ever conducted for ampullary adenocarcinoma. The results suggest a benefit for adjuvant monochemotherapy in patients with clear resection margins.