A phase 2 trial of gemcitabine, 5‐fluorouracil, and radiation therapy in locally advanced nonmetastatic pancreatic adenocarcinoma

Abstract

BACKGROUND:The purpose of this study was to assess the efficacy and safety of 5-fluorouracil (5FU) and gemcitabine administered concurrently with radiation in patients with locally advanced, nonmetastatic pancreatic cancer. METHODS: Eligible patients had histologically confirmed pancreatic adenocarcinoma deemed locally unresectable without evidence of metastatic disease. In addition, all patients underwent laparoscopy or laparotomy before study entry to rule out peritoneal carcinomatosis. Patients received radiation therapy (50.4 Gy) with concurrent infusional 5FU (200 mg/m 2 5 days/week) and weekly gemcitabine (200 mg/m 2 ). After a 3-week break, patients received weekly gemcitabine at 1000 mg/m 2 for 3 of 4 weeks, for 4 cycles. The primary endpoint of the trial was the proportion of patients surviving 9 months from study entry. Secondary endpoints included objective tumor response, CA19-9 response, overall survival (OS) time to progression (TTP), and toxicity. RESULTS: Between November 2001 and October 2004, 81 patients were enrolled, 78 of whom were eligible for analysis. With a median follow-up of 55.2 months, the median OS was 12.2 months (95% confidence interval [CI], 10.9-14.9) and the median TTP was 10 months (95% CI, 6.4-12.0). An objective tumor response was seen in 19 patients (25%), and among 56 patients with an elevated CA19-9 at baseline, 29 (52%) had a sustained CA19-9 response. Overall, 41% of patients had grade 3 or greater treatmentrelated gastrointestinal adverse events. CONCLUSIONS: The combination of 5FU, gemcitabine, and radiation is well tolerated. Survival is comparable with the best results of other recent studies of 5FU and radiation or gemcitabine and radiation. Cancer 2011;117:2620-8.

Targeting Mitochondrial STAT3 with the Novel Phospho-Valproic Acid (MDC-1112) Inhibits Pancreatic Cancer Growth in Mice

“…Isobolograms established synergy between P-V and 5-FU, GABA, arsenic trioxide and cimetidine (Fig. S2); all are reported to have some effect against PC [19]–[22]. While 5-FU failed to synergize with P-V in vivo (Fig.…”

Advances in systemic therapy for advanced pancreatobiliary malignancies

“…Two recent trials compared chemoradiotherapy with chemotherapy alone and came to a different conclusion, with one suggesting a benefit of adding radiotherapy and the other not 23, 24 . The use of concurrent chemoradiation therapy for locally advanced pancreatic cancer is also supported by phase II studies 25, 26 . Chemoradiotherapy was not found to be superior to chemotherapy alone in a recent systematic review, but the heterogeneity and small size of the included studies makes comparisons difficult 27 .…”

Neoadjuvant gemcitabine, docetaxel, and capecitabine followed by gemcitabine and capecitabine/radiation therapy and surgery in locally advanced, unresectable pancreatic adenocarcinoma

“…The goal of surgery is R0 resection: complete resection with negative tumor margins. When chemotherapy/radiotherapy regimens are used without resection, the median survival is approximately 12 months . R0 resection means negative microscopic margins, but a negative surgical margin is a qualitative observation.…”

“…Various schedules of radiation therapy (RT) with sensitizing chemotherapy have been used to treat patients with locally advanced disease . Neoadjuvant studies designed to increase resectability have often excluded patients with arterial involvement.…”

“…Neoadjuvant studies designed to increase resectability have often excluded patients with arterial involvement. Treatment options include RT in a standard fashion (up to 50.4 Gy) combined with 5‐fluorouracil, capecitabine, and gemcitabine (with or without other agents) or stereotactic RT . To date, no regimen appears to be clearly superior despite differences in patient selection.…”