Chemotherapy and radiotherapy for inoperable advanced pancreatic cancer

Abstract

Background: Pancreatic cancer has a poor prognosis. The benefit of chemotherapy, radiotherapy or both as a palliative treatment of advanced or relapsed disease is uncertain.

Objectives: To assess the effects of chemotherapy and/or radiotherapy in the management of pancreatic adenocarcinoma in people with inoperable advanced disease.

Search strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which includes the Cochrane Upper Gastrointestinal and Pancreatic Diseases (UGPD) Group Trials Register (The Cochrane Library 2005, Issue 1); CANCERLIT (1975-2002); MEDLINE (1966 to January 2005); and EMBASE (1980 to January 2005). We handsearched reference lists from trials revealed by electronic searches to identify further relevant trials. We searched published abstracts from relevant conference proceedings. We contacted colleagues and experts in the field, and asked them to provide details of outstanding clinical trials and any relevant unpublished materials.

Selection criteria: Randomised controlled trials (single- or double-blind) in patients with advanced inoperable pancreatic cancer, in which one of the intervention types (chemotherapy or radiotherapy) was contrasted with either placebo or another type of intervention. Studies comparing non-chemotherapy agents such as biological agents, hormones, immunostimulants, vaccines and cytokines were excluded.

Data collection and analysis: Studies were assessed for eligibility and quality. Data were extracted by groups of two independent reviewers, with conflicts resolved by a third reviewer. Study authors were contacted for more information.

Main results: Fifty trials (7043 participants) were included. Chemotherapy significantly reduced the one-year mortality (odds ratio (OR) 0.37, 95% confidence interval (CI) 0.25 to 0.57, P value < 0.00001) when compared to best supportive care. Also, chemoradiation improved one year survival (0% versus 58%, P value 0.001) when compared to best supportive care. There was no significant difference in one-year mortality for 5FU alone versus 5FU combinations (OR 0.90, 95% CI 0.62 to 1.30); single-agent chemotherapy versus gemcitabine (OR 1.34, 95% CI 0.88 to 2.02, P value 0.17); or gemcitabine alone versus gemcitabine combinations (OR 0.88, 95% CI 0.74 to 1.05). However, subgroup analysis showed that platinum-gemcitabine combinations reduced six-month mortality compared to gemcitabine alone (OR 0.59, 95% CI 0.43 to 0.81, P value 0.001). A qualitative overview suggested that chemoradiation produced better survivals than either best supportive care or radiotherapy. Chemoradiation treatment was associated with more toxicity.

Authors' conclusions: Chemotherapy appears to prolong survival in people with advanced pancreatic cancer and can confer clinical benefits and improve quality of life. Combination chemotherapy did not improve overall survival compared to single-agent chemotherapy. Gemcitabine is an acceptable control arm for future trials investigating scheduling and combinations with novel agents. There is insufficient evidence to recommend chemoradiation in patients with locally advanced inoperable pancreatic cancer as a superior alternative to chemotherapy alone.