Chemotherapy and radiotherapy for inoperable advanced pancreatic cancer.
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.


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


METHODS
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colleagues and experts in the field, and asked them to provide details of outstanding clinical trials and any relevant unpublished materials.


METHODS
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.


METHODS
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.


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.


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.
Yip
D
D
Canberra Hospital, Medical Oncology Unit, Yamba Drive, Garran, ACT, Australia 2605. dyip@med.usyd.edu.au
Karapetis
C
C
Strickland
A
A
Steer
C B
CB
Goldstein
D
D
D000970:Antineoplastic Agents / Q000627:therapeutic use; D003131:Combined Modality Therapy / Q000379:methods; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D003841:Deoxycytidine; D005472:Fluorouracil; D000093542:Gemcitabine