Neoadjuvant chemoradiation in pancreatic and duodenal carcinoma. A phase II study

Abstract

Background. Low resectability rate and high locoregional recurrence are major factors contributing to the failure of surgical treatment for localized pancreatic adenocarcinoma. A Phase II study involving preoperative 5‐fluorouracil (5‐FU) and mitomycin C and radiation therapy was evaluated. Methods. Thirty‐one patients with biopsy‐proven carcinoma (24, head of pancreas; 2, body; 5 duodenum) were treated with preoperative radiation therapy, 5040 cGy (180 cGy/fraction, 5 days/week), concurrent with 5‐FU, 1000 mg/m2/day continuous infusion (days 2–5, 28–32) and mitomycin C 10mg/m2 bolus (day 2). Ten patients had previous laparotomy or bypass surgery and were deemed unresectable; 21 had percutaneous, endoscopic retrograde choleangiopancreatic, or transhepatic stent biopsies. Results. Toxicity included neutropenic fever (2 patients), biliary sepsis (2 patients), and nausea and vomiting requiring total parenteral nutrition. One patient died of biliary sepsis before completion of chemoradiation and 11 patients showed evidence of metastatic disease (clinical or occult). Resectability rate was 38% (10/26) for pancreatic carcinoma and 80% (4/5) for duodenal carcinoma. Pathology of the resected specimens revealed extensive necrosis and hyalinization with clear margins in all cases. Lymph node metastases were found in one case of pancreatic carcinoma. The four resected duodenal carcinomas contained no residual tumor in the specimens. At a median follow‐up of 29 months, the median survival time for those with pancreatic carcinoma was not yet reached in the resection group and was 8 months in the nonresection group. The corresponding actuarial 5‐year survival rates were 58% and 0%, respectively. Conclusions. Neoadjuvant chemoradiation therapy was given safely to patients with pancreatic and duodenal carcinoma. It facilitated complete resection in 38% of patients with pancreatic carcinoma and 80% of those with duodenal carcinoma. A significant downstaging of positive margins and regional lymph nodes occurs as a result of preoperative chemoradiation.

The Royal Marsden experience of small bowel adenocarcinoma treated with protracted venous infusion 5-fluorouracil

“…Although the series is small, the results in terms of overall survival, symptomatic responses, the improvement or maintenance of a good PS as an indicator of quality of life and the generally low toxicity of therapy, suggests that there may be benefit of 5FU-based chemotherapy compared with palliative surgery alone (Sakker and Ware, 1973;Rotman et al, 1994). Various series or case reports have suggested that small bowel adenocarcinoma is a chemo-or radiosensitive disease, particularly in comparison with pancreatic cancer (Sakker and Ware, 1973;Jigyasu et al, 1984;Okhusa et al, 1991;Yeung et al, 1993;Coia et al, 1994). A series of fourteen patients, collected over a 30-year period and treated predominantly with 5-fluorouracil (5FU) containing regimens, reported one partial response (PR) lasting 12 weeks and 11 patients with minor responses or stable disease.…”

“…The role of radiotherapy and chemotherapy is less clear. There are reports of prolonged survival with combination chemo-and radiotherapy following palliative bypass surgery or incomplete resection and reports suggesting a better prognosis compared with pancreatic carcinoma (Sakker and Ware, 1973;Yeung et al, 1993). Data on the use of chemotherapy alone are limited.…”

Chemotherapy for pancreatic cancer

“…[167][168][169] To date there have been no large randomised controlled trials of neoadjuvant therapy, so the evidence of its use remains entirely circumstantial. [170][171][172][173][174][175] These studies sometimes appear to provide spectacular results, but are often based on highly selected patients analysed using retrospective data collection and sub-group analyses. Snady et al reported a median survival of 23.6 months in 68 patients with locally invasive 'unresectable' pancreatic adenocarcinoma who had preoperative chemoradiotherapy (split-course radiotherapy plus 5-FU, streptozocin and CDDP), whilst 91 other patients who underwent a resection had a median survival of only 14 months.…”

Pancreatic cancer

“…However, the impact of neoadjuvant therapy on survival is not clear. 55,56 Palliative treatment using radiation therapy with low-dose 5-FU as a radiosensitizer increased survival for patients with locally unresectable pancreatic cancer (Fig. 5).…”