5-fluorouracil-based chemoradiation in unresectable pancreatic carcinoma: Phase I-II dose-escalation study.

PURPOSE: A Phase I-II dose-escalation study was performed to evaluate the possible impact of the dose on response, toxicity, pain relief, and outcome in patients with unresectable pancreatic carcinoma. METHODS AND MATERIALS: A total of 50 patients entered the study. The external beam radiotherapy (RT) dose was 39.6 Gy in the first 15 patients, 50.4 Gy in the next 15 patients, and 59.4 Gy in the remaining 20 patients, at five 1.8-Gy fractions weekly. During external beam RT, patients received concurrent continuous infusion of 5-fluorouracil (1000 mg/m(2) on Days 1-4 and 21-24). Patients were evaluated for toxic reactions, local disease control, survival, and pain relief. RESULTS: No treatment-related deaths occurred from acute toxicity. Four patients required a temporary treatment interruption because of acute hematologic (2 patients) or GI (2 patients) toxicity, not correlated with the delivered RT dose. Three patients (6%) developed late toxicity (duodenal ulcer in 2 and duodenal stenosis in 1). All patients who developed late toxicity had received a dose of 59.4 Gy. At univariate analysis, only the RT dose correlated significantly with the incidence of late toxicity (at 2 years, 39.6-50.4 Gy resulted in 0% and 59.4 Gy resulted in 58.2%; p = 0.023). At multivariate analysis, the RT dose also showed a trend with the incidence of late side effects (p = 0.052). Overall, 6 patients had a partial response (12%) and 44 (88%) had no change. The overall response rate was 8.0% (95% confidence interval, 1.5-20.5%). The rate of response was not different in the three groups. In-field locoregional disease progression was seen in 7 patients (14.0%). Distant relapse was documented in 34 patients (68.0%). None of analyzed variables, in particular, the RT dose delivered, showed a statistically significant correlation with objective response, local control, incidence of metastasis, disease-free survival, or overall incidence of pain symptoms after therapy. The whole group median survival was 9 months. The actuarial survival rate at 1, 2, and 3 years was 31.3%, 2.8%, and 0.0%, respectively. None of analyzed parameters correlated significantly with survival at univariate or multivariate analysis. CONCLUSION: In a Phase I-II study, the association of high RT doses with the incidence of severe toxicity in the treatment of unresectable pancreatic carcinoma was confirmed. Furthermore, this dose-escalation study did not document a clearcut correlation, using 5-fluorouracil-based chemoradiation, between the radiation dose and clinical outcome.

Pain relief with short-term irradiation in locally advanced carcinoma of the pancreas.

OBJECTIVES: To evaluate whether a short radiation treatment (30 Gy, 3.0 Gy/fraction) had analgesic efficacy in patients with unresectable pancreatic carcinoma. METHODS: Twelve patients were included in this analysis. Before starting and at four weeks after radiation therapy, pain intensity was evaluated and analgesic drug therapy was adjusted until a 0-3 pain score was reached (WHO). RESULTS: No radiotherapy interruptions, no hospitalisation due to toxic reactions, and no severe toxicity were observed. Six patients (50%) had pain control without pharmacological therapy, three patients (25%) reduced their use (35%-72%) of analgesics, while in the remaining three patients (25%) there was no change in analgesic use. Overall, mean reduction in the use of analgesics was 63.1% +/- 43.8%. During follow-up (44 months), two patients (16.7%) showed a worsening of pain that required increased analgesia; in one patient, percutaneous splanchnicectomy was necessary. CONCLUSION: In patients excluded from standard concomitant chemoradiation, hypofractionated-accelerated radiotherapy is feasible and results in pain relief in most patients, documented as a reduced need for analgesics.