Adjuvant gemcitabine and concurrent radiation for patients with resected pancreatic cancer: a phase II study

Abstract

The safety and efficacy of gemcitabine and concurrent radiation to the upper abdomen followed by weekly gemcitabine in patients with resected pancreatic cancer was determined. Patients with resected adenocarcinoma of the pancreas were treated with intravenous gemcitabine administered twice-weekly (40 mg m À2) for 5 weeks concurrent with upper abdominal radiation (50.4 Gy in 5 1 2 weeks). At the completion of the chemoradiation, patients without disease progression were given gemcitabine (1000 mg m À2 ) weekly for two cycles. Each cycle consisted of 3 weeks of treatment followed by 1 week without treatment. Forty-seven patients were entered, 46 of whom are included in this analysis. Characteristics: median age 61 years (range 35 -79); 24 females (58%); 73% stage T3/T4; and 70% lymph node positive. Grade III/IV gastrointestinal or haematologic toxicities were infrequent. The median survival was 18.3 months, while the median time to disease recurrence was 10.3 months. Twenty-four percent of patients were alive at 3 years. Only six of 34 patients with progression experienced local regional relapse as a component of the first site of failure. These results confirm the feasibility of delivering adjuvant concurrent gemcitabine and radiation to the upper abdomen. This strategy produced good local regional tumour control. Cure with surgery alone for patients with operable pancreatic adenocarcinoma remains infrequent. A small randomised trial reported by the Gastrointestinal Study Group (GITSG) demonstrated an improvement in median and overall survival for patients treated with a surgical resection who were randomised to adjuvant 5-fluorouracil-based chemoradiation (vs observation) (1987). The chemoradiation consisted of bolus 5-fluorouracil (5-FU) and split course radiation to a total dose of 40 Gy. The median and 2-year survival for the surgery alone patients was 11 months and 18% vs 20 months and 43%, respectively, for the patients receiving adjuvant therapy. The European Organization for the Research and Treatment of Cancer (EORTC) attempted to replicate the results of the GITSG trial but failed to confirm a statistical benefit, despite a 4.5-month improvement in median survival for patients receiving adjuvant chemoradiation (Klinkenbijl et al, 1999). In an update of the European Study for Pancreatic Cancer (ESPAC 1) trial, six cycles of adjuvant 5-FU chemotherapy given alone or following split-course 5-FU-based chemoradiation appeared to provide a survival benefit over surgery alone (Neoptolemos et al, 2004). While the results of the ESPAC trial leave in question the role of radiation therapy in this setting, the use of chemoradiation reflects an accepted standard in the United States.Gemcitabine is active as a single agent in the treatment of pancreatic cancer (Casper et

Determining Pattern of Recurrence Following Pancreaticoduodenectomy and Adjuvant 5-Flurouracil-Based Chemoradiation Therapy: Effect of Number of Metastatic Lymph Nodes and Lymph Node Ratio

“…Regine et al 32 noted that the addition of gemcitabine before and after 5-FU-based chemoradiation therapy resulted in a nonsignificant improvement in survival compared with 5-FU-based chemoradiation therapy alone, although local control was not specifically reported in this study. Others [33][34][35] have reported that combining irradiation with gemcitabine 33,34 or targeted agents 35 may result in improved local and distant control in patients with resected pancreatic adenocarcinoma. Although in the current study we did not find any association between local recurrence and radiation dose (40 versus 50.4 Gy), doses of >54 Gy may be necessary to improve locoregional outcomes.…”

Long-term Analysis of Gemcitabine-based Chemoradiation after Surgical Resection for Pancreatic Adenocarcinoma

“…However, the acute toxicity reported was higher than in the current study (grade 3 and 4 hematological 26 %, grade 3 and 4 gastrointestinal 13 %). 22 Van Laethem et al investigated in multicenter phase II trial feasibility and toxicity of gemcitabine-based CRT regimen after R0 resection of pancreatic head cancer. After surgery, 90 patients were randomly assigned to receive either 4 cycles of gemcitabine (control arm) or gemcitabine for 2 cycles followed by weekly gemcitabine with concurrent radiation (50.4 Gy; CRT arm).…”

The Role of Adjuvant Chemotherapy for Patients with Resected Pancreatic Cancer: Systematic Review of Randomized Controlled Trials and Meta-Analysis

“…Furthermore, 2 previously published meta-analyses also did not show any consistent benefit for adjuvant CRT [15, 16]. Thus, only well-designed randomized studies using modern CRT regimens (including intensified modulation radiotherapy, 5-FU as continuous infusion or gemcitabine, and even targeted agents) will be able to better define the role of radiation treatment in the adjuvant setting [22,23,24,25]. …”