A prospective phase II study of biweekly S-1, leucovorin and gemcitabine in elderly patients with locally advanced or metastatic pancreatic adenocarcinoma

[[abstract]]Background: A chemotherapeutic regimen for elderly patients with advanced pancreatic cancer is necessary because of the considerable toxicities associated with current standard regimens. A modified combination of gemcitabine, S-1, and leucovorin (GSL) was used as a first-line treatment for elderly patients with newly diagnosed locally advanced or metastatic pancreatic adenocarcinoma in a prospective, phase II, multicenter clinical trial (NCT03559348). Methods: Patients more than 70 years of age with ECOG performance status score 0-2 were treated with GSL. GSL was administered every 2 weeks, intravenous gemcitabine 800 mg/m2 at a fixed-dose rate of 10 mg/m2/min on day 1 and oral S-1 (80-120 mg/day) plus leucovorin 30 mg twice daily on days 1-7, until disease progression, withdrawal, or intolerable toxicities. The primary endpoint was progression-free survival (PFS). Results: Overall, 49 patients were enrolled into the trial between 10 July, 2018 and 25 March, 2020, with a median follow-up of 12.5 months. The data cut-off point was on 15 June, 2021. The median patient age at diagnosis was 76 years (range, 70–87 years), and thirty-two (65.3%) patients had metastatic lesions before GSL treatment. Patient frailty was evidenced by the Vulnerable Elders Survey (VES)-13 score (median 5, range 0-13) and Geriatric 8 (G8) score (median 10.5, range 3-15) at baseline. Among the 44 evaluable patients, 13 demonstrated a partial response (29.5%) and 24 presented with stable disease (54.5%). The median PFS was 6.6, 6.6, and 6.3 months, and OS was 12.5, 12.7, and 11.6 months for total population, patients with locally advanced disease, and patients with metastatic lesions, respectively. Patients had improved emotional function and global health status score during GSL treatment. The most frequent grade 3 or higher treatment-related toxicities included anemia (20.4%), decreased neutrophils (18.4%), decreased white blood cells (16.3%), and oral mucositis (12.2%). Conclusions: The GSL regimen results in impressive efficacy with tolerable toxicity in this group of frail patients. In addition, quality of life can be maintained during the treatment. GSL could be a treatment of choice for elderly patients with locally advanced or metastatic pancreatic cancer. Clinical trial information: NCT03559348