Updated 1 November 2005

Even in cases of pancreatic cancer that are resectable, the 5-year survival rate is only 15% to 20%.⁽³⁾ Despite apparently complete removal of the primary tumour, patients relapse with both distant metastases and local-regional recurrences.  As a result, there have been a number of studies combining chemotherapy with radiation given in an adjuvant fashion.

The Gastrointestinal Tumor Study Group (GITSG) conducted a trial using adjuvant chemoradiation.⁽¹²⁾ It was terminated prematurely because of poor accrual and because there appeared to be a clear survival advantage for the treatment arm. The trial randomized 22 patients to surgery alone and 21 patients to surgery followed by bolus 5-fluorouracil (5-FU) with regional split-course radiation to a dose of 40 Gy followed by maintenance 5-FU. The median survival of the treatment group was 20 months compared with 11 months for the control group. There were four patients who survived five years or more – three in the treatment arm, one in the control group. Critics of this study point out the poor accrual (43 patients over 8 years) and the wide confidence intervals.

The European Organization for the Treatment of Cancer (EORTC) attempted to reproduce the results of the GITSG trial. Patients with resected periampullary or pancreatic tumours were randomized to observation or chemoradiotherapy.⁽¹³⁾ Although chemoradiotherapy was not shown to be of benefit in the entire group, subset analysis showed a trend to improved survival with adjuvant therapy in the pancreatic group. Critics of this study point out that it was underpowered (only 81 patients were treated), used a low dose and a split course of radiotherapy, included both R0 (complete) and R1 (microscopically involved margins) resections and used chemotherapy only for the duration of radiotherapy (ie no continued chemotherapy.)

Most recently, the European Study for Pancreatic Cancer (ESPAC)  published the results of the ESPAC-1 trial, which randomized 541 patients with resected pancreas cancer in a two-by-two factorial fashion to:

1. observation;
2. chemotherapy alone (bolus 5-FU 425 mg/m2 + LV 20 mg/m2 IV daily x 5 days, q28 days x 6 cycles);
3. chemoradiotherapy (20 Gy in 10 fractions over 2 weeks with bolus 5-FU 500 mg/m2 IV on first 3 days of radiotherapy; repeated after 2 week break); and
4. chemoradiotherapy  followed by chemotherapy.⁽¹⁴⁾

The median survival in the chemoradiotherapy group was 15.5 months and was not significantly different from that of the observation group (16.1 months, P = 0.24). There was, however, a survival advantage for patients treated with chemotherapy alone (median survival 19.7 months) versus observation. The investigators concluded that there was no benefit to chemoradiotherapy following resection of pancreas cancer. Confounding the interpretation of this study, patients could receive non-trial based therapies (including radiotherapy) at the discretion of the treating oncologist. Accordingly, patients randomized to (and analyzed as) observation may have received cytotoxic therapy. However, this remains the largest adjuvant trial in pancreas cancer published to date. Accordingly, despite the methodologic flaws, the BC Cancer Agency acknowledges that there may be some benefit to adjuvant 5FU-based chemotherapy following curative-intent resection of pancreatic cancer. Selected patients may be offered treatment on the GIPAJFF protocol.

Recently reported and ongoing studies are investigating the role of Gemcitabine in the adjuvant setting.