The combination of gemcitabine
(GemCap) failed to prolong survival
more than gemcitabine (Gem) alone,
although the combination was well
tolerated and easily administered, Richard
Herrmann, MD, of the University
Hospital, Basel, Switzerland, reported
(abstract LBA4010). The study
was supported in part by Hoffmann-
LaRoche and Eli Lilly.
"Patients with good performance
status achieved a significant gain in
median survival of 2.6 months, or 35%,
when treated with GemCap. Therefore,
in patients with advanced cancer
of the pancreas and good performance
status, GemCap seems to be a good
alternative to single-agent treatment,"
Dr. Herrmann said.
A Multi-institutional Study
Dr. Herrmann reported on a multiinstitutional
study of patients with histologic
or cytologic proof of primary
inoperable or metastatic adenocarcinoma
of the pancreas, a Karnofsky
performance score (KPS) ≥ 60%, and
no previous chemotherapy. Stratification
factors included locally advanced/
metastatic disease, absence/presence
of pain, institution, and a KPS of 60-
80 vs 90-100.
The primary endpoint was overall
survival, and secondary endpoints
were quality of life, clinical benefit,
objective tumor response (according
to RECIST criteria), duration of response,
time to disease progression,
and toxicity. The investigators hypothesized
that the median overall survival
would be 5 months with gemcitabine
and 7 months for combination gemcitabine/
Better Results With Good
A total of 319 patients were randomized
to receive GemCap (n = 160)
or Gem (n = 159). The treatment protocol
(1,000 mg/m2 IV on days 1 and 8) and
capecitabine (650 mg/m2 twice daily
on days 1-14 every 3 weeks) or gemcitabine
(1,000 mg/m2 weekly x 7, then 1
week rest, and then weekly x 3 every 4
weeks). Treatment continued for 6
months or until disease progression.
Dr. Herrmann cautioned, "Please note
that there are other versions of this
regimen using higher doses of capecitabine
and different schedules." Three
hundred patients were evaluable for
response (148 on GemCap, and 152
The median overall survival was
8.4 months for the GemCap arm
and 7.3 months for the Gem group
(P = .314). Dr. Herrmann pointed out
that survival in the gemcitabine-only
group was 2 months longer than
expected, rendering the difference
between gemcitabine and combined
cant (Table 1).
The confirmed response rate was
10.1% for GemCap vs 7.9% for Gem.
The median duration of response was
7.4 months for GemCap vs 5.9 months
for Gem, and the median time to disease
progression was 4.8 months for
GemCap vs 4.0 months for Gem.
A multivariate Cox regression of
overall survival showed that in patients
with a KPS ≥ 90, those treated
with GemCap had a significantly longer
median overall survival of 10.1
months vs 7.5 months for Gem (P =
"Overall, GemCap does not improve
overall survival as compared to
the present standard gemcitabine.
However (as indicated by subgroup
analysis), in patients with a good
performance status, a significant
improvement in median overall survival
of 2.6 months can be achieved,"
Dr. Herrmann said.
In discussing this trial Eileen
O"Reilly, MD (Memorial Sloan-Kettering
Cancer Center, New York) said,
"For now, the control arm of future
trials should remain single-agent gemcitabine."