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Toronto, ON—
Studies are under way to determine the role of CPT-11, oxaliplatin,
capecitabine and rofecoxib in the adjuvant treatment of advanced
colon cancer.
Charles Erlichman, MD, Chief of Oncology, Mayo Clinic, Rochester,
N.Y., summarized the trials at the September conference, New Developments
in Cancer Management, sponsored by Toronto’s Princess Margaret
Hospital.
Currently, treatment for Stage II colon cancer is controversial,
while for Stage III it remains adjuvant 5-fluorouracil/leucovorin
(5-FU/LV). For Stage III rectal cancer, radiation and 5-FU based
chemotherapy is the standard, Dr. Erlichman said.
• Two large trials are assessing the role of CPT-11 in the
adjuvant setting for advanced colon cancer, and results are about
one year away. Intergroup C89803 and PETACC-3 will reveal what the
new standard of treatment will be in terms of where CPT-11 fits
in.
• The addition of oxaliplatin to 5-FU/LV (FOLFOX 4 regimen)
has demonstrated a small disease-free survival benefit over
5-FU/LV alone. Interim results of the MOSAIC Phase III trial were
presented this year at the American Society of Clinical Oncology
meeting. Three-year overall disease-free survival for Stage II and
III patients was reported as 77.9 per cent in the FOLFOX arm versus
72.8 per cent for 5-FU/LV alone.
“These are promising data,” Dr. Erlichman said. “Overall
survival data are not available yet.”
FOLFOX is more
toxic, however. Neuropathy, thombocytopenia, neutropenia, diarrhea
and vomiting were reported.
• To avoid the toxicity problem, comparison of adjuvant capecitabine
to 5-FU/LV is being investigated in a Stage III colon cancer trial
(X-ACT). No data are available yet.
• The National Surgical and Bowel Project has undertaken an
oxaliplatin plus 5-FU/LV versus 5-FU/LV alone trial with more than
2,400 patients entered, using a FLOX regimen.
• The addition of a COX-2 inhibitor is being studied for Stage
II and III colon cancer patients in Europe (the VICTOR trial) and
this trial is expected to enter North America soon, Dr. Erlichman
said. One thousand patients have been accrued (as of September 2003),
with a goal of 7,000 patients. Following either surgery, surgery/RT,
surgery/CT, or all three, patients are randomised to either placebo
or the NSAID rofecoxib, for two or five years.
On the books:
• Intergroup N0147 would compare CPT-11/5F-U/LV and oxaliplatin/5-FU-LV.
Patients would be randomised to either six cycles of FOLFOX 6 or
six cycles of FOLFIRI or a combination of both. The goal is to accrue
3,600 patients.
• The NSABP has proposed Trial C08 to compare FLOX versus FOLFOX
6 versus CAPOX and are proposing to add in in bevacizumab as a randomisation.
Approximately 5,000 patients will be accrued.
• Quasar 2 would look at CPT-11 plus capecitabine versus 5-FU/LV.
CPT-11 plus capecitabine would be easier to give than the latter.
• ECOG has proposed a trial to identify subsets of Stage II
patients who may be at a higher risk. Approximately 3,125 patients
with Stage II cancer are to be accrued. Genetically determined high-risk
patients will receive 5-FU/LV plus bevacizumab, compared to 5-FU/LV
alone.
• The proposed ECOG Replacement Rectal Adjuvant trial would
randomise patients to 5-FU/LV/CPT-11 or 5-FU/LV/oxaliplatin or 5-FU/LV
alone. Patients would be allowed to have pre- or post-op radiation,
in the hope of accruing as many patients as possible.
• The NSABP R04 trial would randomise patients to either continuous
infusion 5-FU or capecitabine, along with asking whether pre-op
erythropoiten would decrease the number of transfusions with the
surgery and improve quality of life. Core biopsies would be obtained
prior to RT, analysed for gene expression, and re-analysed after
treatment. The intent is to identify gene patterns that will predict
responders and non-responders to pre-op CT and RT.
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