Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer.
OBJECTIVE
Both gemcitabine (GEM) and fluoropyrimidines are valuable treatment for advanced pancreatic cancer. This open-label study was designed to compare the overall survival (OS) of patients randomly assigned to GEM alone or GEM plus capecitabine (GEM-CAP).


METHODS
Patients with previously untreated histologically or cytologically proven locally advanced or metastatic carcinoma of the pancreas with a performance status <or= 2 were recruited. Patients were randomly assigned to GEM or GEM-CAP. The primary outcome measure was survival. Meta-analysis of published studies was also conducted.


RESULTS
Between May 2002 and January 2005, 533 patients were randomly assigned to GEM (n = 266) and GEM-CAP (n = 267) arms. GEM-CAP significantly improved objective response rate (19.1% v 12.4%; P = .034) and progression-free survival (hazard ratio [HR], 0.78; 95% CI, 0.66 to 0.93; P = .004) and was associated with a trend toward improved OS (HR, 0.86; 95% CI, 0.72 to 1.02; P = .08) compared with GEM alone. This trend for OS benefit for GEM-CAP was consistent across different prognostic subgroups according to baseline stratification factors (stage and performance status) and remained after adjusting for these stratification factors (P = .077). Moreover, the meta-analysis of two additional studies involving 935 patients showed a significant survival benefit in favor of GEM-CAP (HR, 0.86; 95% CI, 0.75 to 0.98; P = .02) with no intertrial heterogeneity.


CONCLUSIONS
On the basis of our trial and the meta-analysis, GEM-CAP should be considered as one of the standard first-line options in locally advanced and metastatic pancreatic cancer.
Cunningham
David
D
Royal Marsden National HealthService (NHS) Foundation Trust, London and Surrey, United Kingdom. david.cunningham@rmh.nhs.uk
Chau
Ian
I
Stocken
Deborah D
DD
Valle
Juan W
JW
Smith
David
D
Steward
William
W
Harper
Peter G
PG
Dunn
Janet
J
Tudur-Smith
Catrin
C
West
Julia
J
Falk
Stephen
S
Crellin
Adrian
A
Adab
Fawzi
F
Thompson
Joyce
J
Leonard
Pauline
P
Ostrowski
Joe
J
Eatock
Martin
M
Scheithauer
Werner
W
Herrmann
Richard
R
Neoptolemos
John P
JP
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000069287:Capecitabine; D016001:Confidence Intervals; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D011336:Probability; D016016:Proportional Hazards Models; D011788:Quality of Life; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D006113:United Kingdom; D000093542:Gemcitabine
D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil; D000093542:Gemcitabine