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Intended
Audiences:
Oncology clinicians
Overview:
Dr. Jean Maroun, Chair of the Editorial
Committee of the Canadian Oncology website site and
Medical Oncologist with the Ottawa Regional Cancer
Centre and Medical Oncologist, Dr. Anthony Fields,
President of the National Cancer Institute of Canada
(NCIC) & Vice President, Medical Affairs and Community
Oncology, Alberta Cancer Board discuss and Dr. Ralph
Wong, Medical Oncologist CancerCare Manitoba, St.
Boniface General Hospital, review major issues arising
from the Annual Meeting of the American Society
of Clinical Oncology 2003 and The 5th International
Conference: Perspectives in Colorectal Cancer (PICC
2003) in Barcelona pertaining to the treatment
of colorectal cancer.
The
issues include:
1st
& 2nd line treatment of metastatic colorectal
cancer
A review of Goldberg’s Intergroup N9741 randomized
trial comparing CPT-11 + 5-FU/LV (IFL), Oxaliplatin
+ 5-FU/LV (FOLFOX4), or Oxaliplatin + CPT-11 (IROX).
While Folfox has been shown to be superior to IFL
in the first-line treatment of metastatic disease,
the question remains whether Folfox is equivalent
to the other infusion schedule, Folfiri. (Briefly
explain Folfiri vs. Folfox). Question: What conclusions
concerning the treatment of advanced colorectal cancer
can we draw from the results of this study?
The
data from Rothenberg trial (EFC 4584) in the second-line
treatment of metastatic CRC after failure of irinotecan
has shown Folfox to be superior to 5FU-leucovorin
or Oxaliplatin alone, in terms of survival, time-to-progression
and response rate. Question: What conclusions can
be drawn from this study regarding the treatment of
Stage II CRC?
Novel
Biotherapeutics
Improvement to the IFL metastatic CRC regimen with
the addition of biotherapeutic angiogenesis inhibitor
Avastin (bevacizumab). However, would it improve treatment
in combination with Folfiri? Question: In light of
the Avastin (bevacizumab) Phase III study presented
at ASCO this year, how do you expect this data will
effect treatment in the clinical setting? Should it
be incorporated into standard treatment or is it just
interesting but requires more investigation? What
type of studies?
The
Cunningham data on the use of monoclonal antibody,
C-225 VE-cadherin Inhibitor, has shown it inhibits
angiogenesis, tumor growth and metastasis by blocking
the ability of VE-cadherin to form tubular structures.
Efforts are underway to optimize the specificity of
these antibodies to recognize only VE-cadherin, thereby
avoiding potential adverse effects on existing vasculature.
Question: What role should C-255 play in second or
third-line therapy?
The
results of MOSAIC trial by De Grandmont show Folfox
is superior to 5FU-leucovorin in terms of disease-free
survival, but there is not data on overall survival.
It is the first indication that combination chemotherapy
is better than standard mono-therapy in adjuvant CRC.
Question:Given the XELIRI and XELOX Phase II Data
(explain) would you use Xeloda (capecitabine) in combination
instead of the infusion?
NOTES: |
R.M.
Goldberg
Intergroup N9741 randomized patients with CRC
between CPT-11 + 5-FU/LV (IFL), Oxal + 5-FU/LV
(FOLFOX4), or Oxal + CPT-11 (IROX). FOLFOX4
resulted in improved RR, TTP, and OS compared
with both IFL and IROX. Considering grade 3
or greater toxicity, the FOLFOX4 regimen is
the most favorable of these 3 regimens. Observed
differences in specific aspects of QOL but not
overall QOL have implications for future study
design. Based on these results, FOLFOX4 should
be considered a first-line standard for advanced
CRC. FOLFOX4 results in improved RR, TTP, and
OS compared to both IFL and IROX. Considering
grade 3 or greater toxicity, the FOLFOX4 regimen
is the most favorable of these 3 regimens. Observed
differences in specific aspects of QOL but not
overall QOL have implications for future study
design. Based on these results, FOLFOX4 should
be considered a first-line standard for advanced
CRC.
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M.L.
Rothenberg
In North America, no effective therapy has been
available for patients with metastatic colorectal
cancer following irinotecan and bolus 5-FU/LV
(IFL). EFC 4584 randomized patients with progressive
CRC to bolus and infusional 5-FU/LV (LV5FU2) vs.
single agent oxaliplatin (OXALI) vs. the combination
(FOLFOX4) consisting of oxali 85 mg/m2 d 1 + LV
200 mg/m2, 5-FU 400 mg/m2 bolus + 600 mg/m2 as
a 22 hour infusion. An interim analysis of the
first 463 patients demonstrated that, compared
with the control arm longer TTP and a higher rate
of relief from tumor-related symptoms. (Rothenberg
et al: Ann Oncol 13 (Supp 5):2,2002). Safety analysis
in 789 assessable pts: (table) Final efficacy
analysis can commence after 393 deaths have occurred
on the LV5FU2 and FOLFOX4 arms (~ Jan, 2003).
Final intent-to-treat analysis on ~817 patients
for efficacy, which will include a comparison
of overall survival and time-to-tumor symptom
worsening, will be performed in Mar, 2003 with
the results available for presentation.
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| At
ASCO, in June of this year, it was announced that
a randomized, Phase III study in previously-untreated
metastatic colorectal cancer patients evaluating
biotherapy Avastin™ (bevacizumab, rhuMAb-VEGF)
plus chemotherapy versus chemotherapy alone improved
overall survival, as measured by a hazard ratio.
Patients receiving Avastin plus chemotherapy had
a 50-percent increase in survival, compared with
patients who received chemotherapy alone. Conversely,
this corresponds to a hazard ratio of 0.65 (p=0.00003).
Overall survival data suggest a stronger patient
benefit than anticipated (the study was designed
to detect a hazard ratio of 0.75, or a 33 percent
increase in chance for survival).
Results from a second Genentech
study in metastatic colorectal cancer are expected
later this year. The second colorectal cancer
trial enrolled 200 not optimal candidates for
CPT-11 as a first-line treatment and randomized
patients to receive either 5-FU/Leucovorin chemotherapy
alone or in combination with Avastin. |
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