Pilot study of neoadjuvant chemotherapy with gemcitabine and oral S-1 for resectable pancreatic cancer

Abstract

Results of surgery alone for pancreatic cancer are disappointing. We retrospectively evaluated the efficacy and tolerability of neoadjuvant chemotherapy (NAC) with gemcitabine and oral S-1 in patients with potentially resectable pancreatic cancer. A total of 34 patients with pancreatic ductal adenocarcinoma, radiologically diagnosed preoperatively as having potentially resectable tumors, underwent pancreatic resection with lymphadenectomy at Kanazawa University Hospital. NAC was administered to 13 patients (NAC group). The remaining 21 patients were surgically treated without preoperative chemotherapy (control group). Surgical results were compared between these two groups, with follow-up for at least 24 months. No statistically significant differences were found in the clinicopathological background data (tumor location, age, gender, lymph node metastases, tumor stage and tumor size) between the NAC and control groups. Following preoperative chemotherapy, no patients were judged to be unable to undergo laparotomy, i.e., neither distant metastasis nor tumor progression was observed. Radiologically, all 13 NAC group patients had stable disease, whereas, histopathologically, all tumor specimens showed evidence of tumor cells. The treatment effect was judged by Evans grading to be grade IIa in 11 patients and grade IIb in 2 patients. Toxicity was evaluated in 11 patients. Grade III side effects were regarded as hematological toxicity, i.e., leucopenia (7.7%) and thrombocytopenia (15.4%). Moreover, the incidence of perioperative complications did not differ significantly between the NAC and control groups. The one- and three-year overall survival rates of the NAC group with pancreatic head cancer were 88.9 and 55.6%, respectively, superior to 88.9 and 29.6% in the control group (p=0.055). Therefore, NAC with gemcitabine and S-1 is well tolerated and potentially effective against pancreatic head cancer. A phase I study of NAC with gemcitabine and S-1 is under way in patients with resectable pancreatic cancer.

Meta-analysis of the impact of neoadjuvant therapy on patterns of recurrence in pancreatic ductal adenocarcinoma

“…The most important features of the individual studies that were included in the systematic review and meta‐analysis are summarized in Table 1 6 8, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25. The majority of studies6 8, 16, 17, 18, 19, 20, 21, 22, 23, 24 compared neoadjuvant chemoradiotherapy with primary surgery.…”

“…The majority of studies6 8, 16, 17, 18, 19, 20, 21, 22, 23, 24 compared neoadjuvant chemoradiotherapy with primary surgery. Only a single study25 compared neoadjuvant chemotherapy with primary surgery, and another16 included both neoadjuvant regimens in the analyses. Definitions of resectability rates varied between the studies.…”

“…Recurrences were observed in 53·5 and 65·7 per cent of the patients respectively. Duration of follow‐up ranged from 11 months16 to 30 months25, with an overall median of 18·5 months.…”

“…To analyse the impact of neoadjuvant therapy on local tumour recurrence, 12 studies6 8, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 were identified. Of those undergoing primary surgery, 27·7 per cent developed local recurrence compared with 12·4 per cent in the neoadjuvant group ( Fig .…”

“…In contrast to local recurrence, neoadjuvant therapy did not influence distant recurrence, which developed in 283 (50·2 per cent) of 564 patients in the neoadjuvant group versus 334 (49·6 per cent) of 674 in the surgery‐first group. The estimated RR of the meta‐analysis, which included 11 studies6 8, 16 18, 19, 20, 21, 22, 23, 24, 25, also failed to show any relevant impact of neoadjuvant therapy on the risk of distant metastasis (RR 1·02, 95 per cent c.i. 0·91 to 1·14; P  = 0·78) ( Fig .…”