(Xeloda) shows encouraging activity
when given with preoperative
radiation for locally advanced rectal
cancer, according to multiple investigations.
Use of the oral agent could
also avoid the need for daily intravenous
infusions and the associated inconvenience
Five separate phase II investigations
added a considerable amount of support
for using capecitabine preoperatively
in patients with locally advanced
rectal cancer. Two of the investigations
evaluated capecitabine plus oxaliplatin
(Eloxatin), while three others
evaluated single-agent capecitabine in
Capecitabine Plus Oxaliplatin
"As an oral agent, capecitabine can
greatly simplify chemoradiation,
avoiding the need for time-consuming
and potentially complicated daily
intravenous infusions," according to
Robert Glynne-Jones, MBBS.
Dr. Glynne-Jones, consultant clinical
oncologist with Mount Vernon
Hospital, Northwood, United Kingdom,
is the principal investigator in
one of the two trials suggesting that
capecitabine/oxaliplatin has promising
efficacy and acceptable safety for
patients with locally advanced rectal
cancer (abstract 3575). Capecitabine/
oxaliplatin has already been shown to
be well tolerated and "highly effective"
in first-line treatment of metastatic
colorectal cancer, Dr. Glynne-
Jones and colleagues indicated in their
The phase I/II trial, known as SOCRATES
(from the Scottish Cancer
Registration System) is designed to
evaluate the combination of oral
capecitabine, IV oxaliplatin, and standard
radiotherapy to the pelvic region
(XELOX-RT) followed by surgery in
histologically confirmed rectal adenocarcinoma.
In the phase I portion of the trial,
investigators determined the recommended
doses of capecitabine (650
mg/m2 twice daily for 5 weeks) and
oxaliplatin (130 mg/m2 on days 1 and
29). Data show that XELOX-RT enhanced
surgical resection, according
to the investigators. Of 16 patients
undergoing surgery, an R0 resection
was achieved in 14. Complete responses
were observed in five patients.
In the phase II portion, 62 patients
have been enrolled. While pathology
data from phase II are not yet mature,
safety data reported suggest the recommended
dose is well tolerated.
Grade 3/4 adverse events were seen in
only 10 of 41 patients evaluable for
safety. Hand-foot syndrome (grade 1)
was observed in only two patients.
In a separate phase II study, Belgian
investigators reported preliminary
results suggesting that preoperative
radiotherapy was feasible, with diarrhea
being the only clinically relevant
toxicity (abstract 3552).
Lionel R. Duck, MD, Universit
Catholique de Louvain, Brussels, Belgium,
reported that among 17 resected
rectal specimens, 1 specimen indicated
a pathological complete remission,
and 5 specimens had only
microfoci of residual tumor. All specimens
were reviewed by the same pathologist.
Treatment in this trial consisted of
radiotherapy 5 days a week for 5 weeks
for a total dose of 45 Gy, plus oxaliplatin
50 mg/m2 IV weekly, plus oral
capecitabine 825 mg/m2 twice daily.
Patients received more than 90% of
the planned dose of both oxaliplatin
and capecitabine. In two patients, radiotherapy
was interrupted because
German Study Update
A German study group reporting
at ASCO 2003 (abstract 1113) that
capecitabine plus standard radiotherapy
was "highly effective" as neoadjuvant
therapy for locally advanced rectal
cancer, provided an update this
year. The update confirmed that the
oral agent is "an adequate substitute"
for continuous infusion 5-FU in preoperative
"Oral capecitabine simplifies
chemoradiation, avoiding the unwanted
risks and inconvenience associated
with IV 5-FU," reported to Juergen
Dunst and colleagues from the department
of radiotherapy at Martin-
Luther-University, Halle, and other
study sites in Germany.
The interim analysis of a phase II
trial included clinical response data
for 69 patients. By intent-to-treat analysis,
capecitabine chemoradiation resulted
in clinical complete or partial
remissions in 42 patients (61%). This
enabled R0 resections in 89% of patients
undergoing surgery. Tumor
downstaging was achieved in 62%.
A "low incidence" of grade 3/4 adverse
events was reported by the German
researchers. The most common
adverse event, diarrhea, occurred in
46% of patients, but only four patients
(7%) experienced diarrhea of
grade 3/4 intensity.
Italian and French Trials
Italian and French research groups
also reported results for phase II investigations
of capecitabine chemoradiation.
Encouraged by the positive results
previously reported by the Germans,
the Italian group, led by Antonio De
Paoli, MD, of the National Cancer
Institute-CRO in Aviano, tested a similar
regimen (abstract 3540).
In 53 patients evaluable for safety
and efficacy, complete or partial clinical
response was seen in 31 (58%).
Tumor downstaging was achieved in
29 of 51 patients (57%). Only six of
these patients had grade 3 toxicity and
none had grade 4.
French researchers with the GERCOR
Research Group) group also reported
their phase II experience with preoperative
(abstract 3538). Among the 51 study
patients, 50 underwent surgery and 1
refused. Histopathology showed that
24% had complete response, while
12% had persistence of minimal tumor
cell foci and 23% had additional
tumor downstaging. Tumor-free resection
margins were achieved in every
patient. Adverse events were mainly
gastrointestinal, including three cases
of grade 3 diarrhea.
is well tolerated, and the efficacy
supports further exploration, as a
single agent and as part of new therapeutic
strategies with chemo- and
biological therapies," investigators