Phase I/II trial of carbon-ion radiotherapy with concurrent gemcitabine for patients with locally advanced pancreatic cancer.

Abstract

e15008 Background: Carbon-ion radiotherapy (CIRT) offers the potential advantage of improved dose localization and enhanced biologic effect. The purpose of this trial was to establish the recommended dose of gemcitabine and CIRT, evaluating the tolerance and efficacy of gemcitabine combined with CIRT for the treatment of the patients with locally advanced pancreatic cancer. Methods: Patients with histopathologically proven, locally advanced pancreatic adenocarcinoma, which involved the celiac trunk or superior mesenteric artery without distant metastasis, were eligible for this trial. The radiation fractions were fixed at 12 fractions in 3 weeks, and the dose of gemcitabine and radiation were gradually increased. First, the dose was fixed at 43.2GyE/8 fractions and the gemcitabine dose was increased from 400, to 700 to 1000mg/m2. Subsequently, the gemcitabine dose was fixed at 1000mg/m2 and the radiation dose was increased from 43.2GyE to 55.2GyE by 5% increments. Gemcitabine was administered for 3 consecutive weeks, once a week. Results: Seventy-five patients were registered from April 2007 through February 2012. Of these patients, 71 were clinically eligible for the study. The most common Grade 3 acute toxicities were hematological toxicity (51%) and anorexia (8%). Dose limiting toxicity developed in three patients: Grade 3 gastric ulcer in 1 and Grade 4 leukopenia in 2. No other serious side effects were found. The two-year local control rate and two-year overall survival rate were 40% and 40% in all patients. The median survival time was 21 months. In the high dose group (n=47), in which patients were irradiated with at least 45.6 GyE, the two-year survival rate was 62%. Conclusions: CIRT was well tolerable even when concomitantly administered with the highest dose of gemcitabine (1000mg/m2).