HALLE, Germany-Oral capecitabine
(Xeloda) plus radiation is a highly
effective and well-tolerated neoadjuvant
treatment for locally advanced rectal
The results of an interim analysis of a
German multicenter, phase II study were
reported by Juergen Dunst, MD, of Martin-
Halle, Germany (ASCO abstract 1113).
In describing the basis for the phase II
study, Dr. Dunst explained, "As shown in
our previous phase I dose-finding study
(J Clin Oncol 20:3983-3991, 2002), the
concurrent administration of daily
capecitabine with radiotherapy appears
to be feasible and effective in advanced
rectal cancer. The specific rationale for
this combination is based on experimental
findings that thymidine phosphorylase,
necessary for the final conversion of
capecitabine and predominantly present
in tumor cells, is upregulated by radiotherapy
in malignant but not in healthy
"The objective of the present expanded
phase II trial is to establish the use of
this combined modality approach in a
multicenter setting, focusing on its application
as neoadjuvant treatment of cT3,
cT4, fixed or primarily inoperable tumors,"
Dr. Dunst continued.
"Oral capecitabine simplifies chemoradiation
by avoiding the need for timeconsuming
and complicated IV infusions,"
Dr. Dunst noted. "Capecitabine is
a highly effective, first-line treatment for
metastatic colorectal cancer, and it has an
improved safety profile compared with
IV fluorouracil/leucovorin in both the
metastatic and adjuvant settings."
A total irradiation dose of 50.4 to 55.8
Gy was administered in conventional daily
doses of 1.8 Gy over a period of approximately
6 weeks. Capecitabine was given
at an oral dosage of 825 mg/m2 bid on each
day of the radiotherapy period, including
the weekends, with the first daily dose
given 2 hours before irradiation.
So far, 46 patients (60% male, 40%
female) have been recruited from six university
clinics in Germany since June 2001.
The mean age was 65 years, with an Eastern
Cooperative Oncology Group performance
status of 0 or 1. Clinical staging
revealed T3 tumors (48%) and T4 tumors
(52%), and involved lymph nodes (cN+)
Data from 25 patients were available
for the interim analysis. "Capecitabine/
radiotherapy achieved a high clinical response rate," Dr. Dunst reported. "There
was a clinical complete response or partial
response in 72% of patients. Only 12%
experienced disease progression during
neoadjuvant treatment. The high clinical
response rate with capecitabine/radiotherapy
was accompanied by a high rate of R0
resections and tumor downstaging."
Dr. Dunst reported that the comparison
of initial diagnosis and pathologic
findings showed downstaging in 72% of
patients, mainly from cT4 to pT3 to pT0.
Only 8% of patients remained inoperable
at the end of the irradiation period.
Oral capecitabine was well-tolerated
in combination with radiotherapy. The
most commonly reported adverse events
were diarrhea, local erythema, neurologic
pain, and nausea. The only grade 3 adverse
events were diarrhea in two patients
and local erythema in one patient. There
were no grade 4 adverse events. "Oral
a favorable and predictable safety profile,"
Dr. Dunst said. "The majority of
adverse events were mild to moderate in
intensity and there were no grade 4 adverse
events or laboratory abnormalities."
Summarizing the interim results, Dr.
Dunst said, "Oral capecitabine/radiotherapy
achieved clinical responses in 72% of
patients, enabling R0 resections in 89% of
patients undergoing surgery. Seventy-nine
percent of patients undergoing resection
experienced pathologically confirmed tumor
downstaging. Oral capecitabine simplifies
chemoradiation, avoiding the problems
and inconvenience associated with