A multicenter phase II study of gemcitabine and S-1 combination therapy (GS therapy) in patients with metastatic pancreatic cancer

Abstract

4550 Background: As shown in our previous phase I study (Oncology 2005, 69:421–427), gemcitabine and S-1 combination therapy (GS therapy) appears to be feasible and effective against advanced pancreatic cancer. The present multicenter phase II study was conducted to confirm the efficacy and toxicity of GS therapy for metastatic pancreatic cancer. Methods: Patients with histologically or cytologically proven pancreatic adenocarcinoma with at least one measurable metastatic lesion were eligible for the study. Other eligibility criteria included: no previous treatment for pancreatic cancer except surgery, age =20 and =74 years, ECOG performance status of 0 or 1, and adequate organ function. Gemcitabine was given intravenously at a dose of 1,000 mg/m2 over 30 min on days 1 and 8, and S-1 was given orally at a dose of 40 mg/m2 twice daily from day 1 to day 14, repeated every 3 weeks. The objective response rate was assessed according to RECIST. Results: A total of 55 patients from 10 institutions were enrolled between October 2004 and July 2005. The efficacy and toxicity were analyzed in 54 patients who received at least one course of GS therapy. The median number of treatment courses was 7 (range, 1–24+). Although no complete response was seen, a partial response was achieved in 24 patients, resulting in an overall response rate of 44% (95% CI, 30.9–58.6%). Twenty-six patients (48%) had stable disease. The median progression-free survival was 5.9 months (95% CI, 4.1–6.9 months) and the median overall survival was 10.1 months (95% CI, 8.5–10.8 months) with a 1-year survival rate of 33%. The major grade 3–4 toxicities were neutropenia (80%), leucopenia (59%), thrombocytopenia (22%), anorexia (17%), rash (7%), nausea (6%) and fatigue (6%). Hematological toxicity was mostly transient and there was only one episode of infection with grade 3–4 neutropenia. No treatment-related deaths occurred during the study. Conclusions: GS therapy produced a high response rate and good survival associated with an acceptable toxicity profile in patients with metastatic pancreatic cancer. A randomized phase III trial to confirm the efficacy of GS therapy is planned. No significant financial relationships to disclose.

Present status and perspective of perioperative chemotherapy for patients with resectable pancreatic cancer in Japan

“…The median OS was 36.7 months in the NAC-GS group and 26.6 months in patients who received upfront surgery (HR 0.72, 95% CI 0.55-0.94, p = 0.015). Although grade 3 or 4 adverse events of leucopenia and neutropenia were frequently (73%) observed in the NAC-GS group, there was no significant difference between groups with respect to perioperative outcomes including R0 resection rate and post-operative morbidity (26,29). A significant decrease in pathological nodal metastases in the NAC-GS group (60%) was noted compared to upfront surgery (82%) for resected patients (p < 0.01).…”

Oxaliplatin-Induced Hyperammonemic Encephalopathy in a Patient with Metastatic Pancreatic Cancer: A Case Report

“…Currently, FOLFIRINOX (5-fluorouracil [5-FU], oxaliplatin, and irinotecan) and gemcitabine plus nab-paclitaxel are standard therapies for metastatic pancreatic adenocarcinoma. However, many clinical trials have used other regimens, including GEMOX, gemcitabine plus cisplatin, or gemcitabine plus S-1 [ 2 , 3 , 4 ]. Especially in the case of patients who have a family history of either breast, ovarian, or pancreatic cancers, chemotherapy including a platinum agent is associated with a better survival rate [ 5 ].…”

Systemic therapy for metastatic pancreatic adenocarcinoma

“…The oral 5-FU pro-drug, S1, combined with gemcitabine has achieved response rates above 40% in four phase II trials in Japanese patients [Lee et al 2008b;Sudo et al 2008;Ueno et al 2007b;Nakamura et al 2006], and 17% in a fifth trial [Ohkawa et al 2007]. Phase III studies are underway.…”