Clinical investigation: pancreas
Length and quality of survival after external-beam radiotherapy with concurrent continuous 5-fluorouracil infusion for locally unresectable pancreatic cancer

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Abstract

Purpose: The purpose of this study was to evaluate whether external-beam radiotherapy (EBRT) with concurrent continuous 5-fluorouracil (5-FU) infusion affects the length and quality of survival in patients with locally unresectable pancreatic cancer.

Methods: Thirty-one patients with histologically proven locally advanced and unresectable pancreatic cancer without distant metastases were evaluated in this prospective randomized trial. Sixteen patients received EBRT (50.4 Gy/28 fractions) with concurrent continuous infusion of 5-FU (200 mg/m2/day), whereas 15 patients received no chemoradiation. The length and quality of survival was analyzed and compared for the two groups.

Results: The median survival of 13.2 months and the 1-year survival rate of 53.3% in the chemoradiation group were significantly better than the respective 6.4 months and 0% in the group without chemoradiotherapy (p = 0.0009). The average monthly Karnofsky score, a quality of life indicator, was 77.1 in the chemoradiation group, which was significantly higher than the 65.5 in the group without chemoradiotherapy (p < 0.0001). The number of hospital days per month of survival was significantly less in the chemoradiation than in the no-therapy group (12.3 vs. 19.0 days, p < 0.05). In the chemoradiation group, 5 patients (31%) had a partial response, and 9 (56%) had radiologically stable disease at a median duration of 6.1 months. The patients who had chemoradiation had a lower rate of liver and peritoneal metastases than patients without chemoradiotherapy (31% vs. 64%). Of 10 patients who experienced pain before chemoradiation, 8 (80%) received pain relief that lasted a median of 5.2 months.

Conclusions: EBRT with concurrent continuous 5-FU infusion increased the length and quality of survival as compared to no chemoradiotherapy and provided a definite palliative benefit for patients with unresectable pancreatic cancer.

Introduction

Pancreatic cancer is a morbid disease with a dismal prognosis. At present, complete surgical resection offers the best chance of cure 1, 2, 3. However, because of the invasion of major vessels or the presence of metastasis, most pancreatic cancers are already unresectable at the time of diagnosis 4, 5. Without surgical intervention, the mean length of survival is approximately 6 months. Thus, in the majority of patients, optimal palliation of symptoms is of primary importance, to maximize the quality of remaining life 6, 7, 8. Consequently, many studies have recommended radiation therapy and/or chemotherapy as the primary treatment for patients with unresectable tumors of the pancreas. For patients with locally unresectable disease, the results of previous randomized trials by the Gastrointestinal Tumor Study Group indicated that concurrent external-beam radiation therapy (EBRT) and bolus 5-fluorouracil (5-FU) therapy resulted in significantly better survival compared with EBRT alone or chemotherapy alone 9, 10. Recently, radiation has been employed concurrently with systemic, continuous infusion of 5-FU chemotherapy as a radiation sensitizer 11, 12.

We have delivered EBRT with concurrent continuous 5-FU chemotherapy since 1997. In this study, we performed a randomized trial of locally unresectable pancreatic cancer cases. The length and quality of survival of patients who were treated with EBRT plus concurrent continuous 5-FU chemotherapy was compared to the length and quality of survival of those who received no chemoradiotherapy.

Section snippets

Patients

Between January 1997 and June 2000, 31 patients were enrolled in a prospective randomized study at the Kagoshima University Hospital in Kagoshima, Japan. Fifteen of the patients were male, and the mean age of all patients was 64 years (range: 22–82 years). All patients had locally advanced and unresectable pancreatic cancer without distant metastases. Histologic or cytologic confirmation of pancreatic adenocarcinoma was established in all patients. Tumors were considered to be unresectable

Length of survival

The length of survival of all 31 patients ranged from 2.0 to 16.9 months. The mean and median lengths of survival and 1-year survival rate for all 31 patients were 8.5 months, 8.2 months, and 29.6%, respectively. The length and quality of survival for patients in both groups are summarized in Table 2. The mean survival of 10.7 months in the chemoradiation group was significantly longer than the mean survival of 6.2 months in the no-therapy group (p = 0.001). In addition, the median survival of

Discussion

Earlier trials performed by the Gastrointestinal Tumor Study Group established roles for 5-FU chemotherapy and EBRT in the treatment of patients with resectable or locally advanced pancreatic cancer 9, 10, 17, 18. Since then, EBRT concurrent with 5-FU has been generally accepted as the standard treatment for locally advanced pancreatic cancer 19, 20, 21, 22. In all the studies noted above, 5-FU was administered by bolus injection as a radiation sensitizer. Recently, the Eastern Cooperative

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