Multicenter Phase II Study of Intravenous and Intraperitoneal Paclitaxel With S-1 for Pancreatic Ductal Adenocarcinoma Patients With Peritoneal Metastasis

OBJECTIVE:To evaluate the clinical efficacy and tolerability of intravenous (i.v.) and intraperitoneal (i.p.) paclitaxel combined with S-1, "an oral fluoropyrimidine derivative containing tegafur, gimestat, and otastat potassium" in chemotherapy-naive pancreatic ductal adenocarcinoma (PDAC) patients with peritoneal metastasis.BACKGROUND:PDAC patients with peritoneal metastasis (peritoneal deposits and/or positive peritoneal cytology) have an extremely poor prognosis. An effective treatment strategy remains elusive.METHODS:Paclitaxel was administered i.v. at 50 mg/m and i.p. at 20 mg/m on days 1 and 8. S-1 was administered at 80 mg/m/d for 14 consecutive days, followed by 7 days of rest. The primary endpoint was 1-year overall survival (OS) rate. The secondary endpoints were antitumor effect and safety (UMIN000009446).RESULTS:Thirty-three patients who were pathologically diagnosed with the presence of peritoneal dissemination (n = 22) and/or positive peritoneal cytology (n = 11) without other organ metastasis were enrolled. The tumor was located at the pancreatic head in 7 patients and the body/tail in 26 patients. The median survival time was 16.3 (11.47-22.57) months, and the 1-year survival rate was 62%. The response rate and disease control rate in assessable patients were 36% and 82%, respectively. OS in 8 patients who underwent conversion surgery was significantly higher than that of nonsurgical patients (n = 25, P = 0.0062). Grade 3/4 hematologic toxicities occurred in 42% of the patients and nonhematologic adverse events in 18%. One patient died of thrombosis in the superior mesenteric artery.CONCLUSIONS:This regimen has shown promising clinical efficacy with acceptable tolerability in chemotherapy-naive PDAC patients with peritoneal metastasis

Decreased serum carbohydrate antigen 19–9 levels after neoadjuvant therapy predict a better prognosis for patients with pancreatic adenocarcinoma: a multicenter case-control study of 240 patients

Abstract Background Carbohydrate antigen (CA) 19–9 levels after resection are considered to predict prognosis; however, the significance of decreased CA19–9 levels after neoadjuvant therapy has not been clarified. This study aimed to define the prognostic significance of decreased CA19–9 levels after neoadjuvant therapy in patients with pancreatic adenocarcinoma. Methods Between 2001 and 2012, 240 consecutive patients received neoadjuvant therapy and subsequent resection at seven high-volume institutions in Japan. These patients were divided into three groups: Normal group (no elevation [≤37 U/ml] before and after neoadjuvant therapy), Responder group (elevated levels [> 37 U/ml] before neoadjuvant therapy but decreased levels [≤37 U/ml] afterwards), and Non-responder group (elevated levels [> 37 U/ml] after neoadjuvant therapy). Analyses of overall survival and recurrence patterns were performed. Uni- and multivariate analyses were performed to clarify the clinicopathological factors influencing overall survival. The initial metastasis sites were also evaluated in these groups. Results The Responder group received a better prognosis than the Non-responder group (3-year overall survival: 50.6 and 41.6%, respectively, P = 0.026), but the prognosis was comparable to the Normal group (3-year overall survival: 54.2%, P = 0.934). According to the analysis of the receiver operating characteristic curve, the CA19–9 cut-off level defined as no elevation after neoadjuvant therapy was ≤103 U/ml. The multivariate analysis revealed that a CA19–9 level ≤ 103 U/ml, (P = 0.010, hazard ratio: 1.711; 95% confidence interval: 1.133–2.639), tumor size ≤27 mm (P = 0.040, 1.517; (1.018–2.278)), a lack of lymph node metastasis (P = 0.002, 1.905; (1.276–2.875)), and R0 status (P = 0.045, 1.659; 1.012–2.627) were significant predictors of overall survival. Moreover, the Responder group showed a lower risk of hepatic recurrence (18%) compared to the Non-responder group (31%), though no significant difference in loco-regional, peritoneal or other distant recurrence were observed between groups (P = 0.058, P = 0.700 and P = 0.350, respectively). Conclusions Decreased CA19–9 levels after neoadjuvant therapy predicts a better prognosis, with low incidence of hepatic recurrence after surgery