Chemotherapy

Adjuvant treatment in resectable pancreatic cancer

After surgical resection for pancreatic cancer 50-80% of patients may develop local recurrence or metastatic disease usually within the first two years after surgery. Adjuvant treatment has been given in pancreatic cancer in the form of chemo or radiotherapy or in combination. There are numerous trials looking at the effects of chemo and radiotherapy. The best known of these are the ESPAC trials.

ESPAC 1

This was a randomised study to assess the role of adjuvant chemotherapy with 5-FU and folinic acid and adjuvant chemo radiation. This was an extremely important study. It showed that there was no benefit from the addition of chemo-radiotherapy after surgery whereas there was benefit for the role of adjuvant chemotherapy alone.

ESPAC 3

This was formulated as a result of the ESPAC 1 study and designed to test two hypotheses. Firstly whether post-operative treatment with chemotherapy drug Gemcitabine or chemotherapy drug 5 fluoro-uracil and folinic acid improved survival compared to no additional treatment following surgery to remove pancreatic cancer, and also to see whether there was any difference in survival between Gemcitabine and 5 F-U as post-operative chemotherapy treatment. The trial design was amended in 2003 and is now called ESPAC 3 (2). This trial is trying to answer the following questions:-

For patients with ductal adenocarcinoma of the pancreas randomised into a two arm study to answer the question whether there is any difference in survival between Gemcitabine and bolus 5 F-U and folinicacid when used as adjuvant treatment therapy following resection. Patients with ampullary, or pancreatic tumours not ductal adenocarcinoma, who have had a curative resection are randomised into a three arm study with either treatment with 5 fluoro-uracil/folinic acid, Gemcitabine or observation alone. The question really is whether adjuvant chemotherapy improves survival compared to no additional treatment and is there any difference between the two different types of chemotherapy. This trial has closed and the results are awaited.

ESPAC 4

This a trial to compare Gemcitabine alone with Gemcitabine and Capecitabine together after surgery to remove cancer of the pancreas.

Palliative chemotherapy in unresectable pancreatic cancer

When surgery is not possible for advanced or inoperable pancreatic cancer there are trials looking at the effect of chemo and radiotherapy for locally advanced pancreatic cancer.

The SCALOP trial is a trial of chemotherapy following by chemo radiotherapy for locally advanced pancreatic cancer. Following an initial course of treatment with Gemcitabine and Capecitabine combination the trial compares the effects of giving chemo-radiotherapy with either Gemcitabine or Capecitabine. The results are awaited.

There are other trials for patients with inoperable pancreatic cancer. There is a trial of Verteporfin photo-dynamic therapy for locally advanced pancreatic cancer which is recruiting in London.

There is a trial of UFT leucovorin and radiotherapy with or without Cetuximab also recruiting in London.

A biomarker identification trial of Tarceva (Erlotinib) in patients with advanced pancreatic cancer is recruiting nationally. The trial looks at the efficacy and safety of Tarceva in patients with advanced inoperable pancreatic cancer.

A trial looking a Gemcitabine and MK-0752 to treat pancreatic cancer is recruiting in London, Cambridge and Leicester. MK-0752 is an anti-cancer drug which has a different mechanism of action from Gemcitabine. As Gemcitabine has been shown to be effective in pancreatic cancer, it is hoped that a combination of the two drugs may improve the effect of Gemcitabine.

There are several other small trials of other agents.

Radiotherapy

Radiotherapy is the use of ionising radiation to destroy cancer cells. Radiotherapy in pancreatic cancer is given externally although there is no reason why this should not be administered from within eventually. Radiotherapy has a role in locally advanced disease when a tumour is felt to be inoperable. A combination of chemo and radiotherapy may effectively shrink the tumour and render it operable. It can also be used in the palliative setting so as to shrink tumours and help relieve symptoms such as pain.