ASCOIn contrast to many recent studies, the ICON3 trial finds
that paclitaxel (Taxol) plus carboplatin (Paraplatin) is no more
effective than other chemotherapy regimens as first-line therapy of
ovarian cancer. ICON3the Third International Collaborative
Ovarian Neoplasm studyis an international multicenter trial
involving 2,074 women with newly diagnosed ovarian cancer requiring
Nicoletta Colombo, MD, vice director, Division of Gynecology,
European Institute of Oncology, Milan, Italy, presented preliminary
results at the 36th Annual Meeting of the American Society of
Clinical Oncology (ASCO), New Orleans.
The trial tested paclitaxel plus car-boplatin against either
carboplatin by itself or cyclophosphamide plus doxorubicin plus
cisplatin (Platinol) (CAP). Dr. Colombo said that because the ICON2
study had found no difference between carboplatin and CAP in
effectiveness, in ICON3 investigators were allowed to choose which
control regimen to use.
However, in a commentary, Robert Young, MD, of Fox Chase Cancer
Center, called this decision a serious flaw in the design of
the trial. One of the basic tenets of randomized clinical trials is
that they not only control for those things you think are important
in outcome, they also control effectively for those things you
dont realize are important.
In ICON3, paclitaxel was given as a 3-hour infusion at 175
mg/kg². The dose of carboplatin was determined by Calverts
area-under-the-curve method. In the CAP control group,
cyclophosphamide was given at 500 mg/m², doxorubicin at 50 mg/m²,
and cisplatin at 50 mg/m². For all groups, treatment was
administered every 3 weeks for six cycles.
The researchers found no differences between the
paclitaxel/carboplatin group and the control groups. At 1 year, the
progression-free survival rate was 61% in the paclitaxel/carboplatin
group vs 60% in the control subjects.
Median progression-free survival was 16.8 months (treatment group) vs
16.2 months (control group). Similarly, overall survival at 2 years
was 64% (treatment) vs 62% (control), with median overall survival of
38.7 months (treatment) vs 36 months (control).
Absence of Significance
I would like to highlight the absence of statistical
significance and the size of the effect we are seeing, Dr.
Colombo said. In other words, even though in the future, given
the large number of patients included in ICON3, we may be able to
pick up a statistically significant difference, this will be probably
in the range of 2% more patients surviving in the research arm
compared to the controls.
Both Drs. Colombo and Young pointed out that these results are at
odds with some other studies of paclitaxel plus a platinum-based
agent. In those studies, women in the control arm had shorter
progression-free survival and overall survival than in ICON3.
Dr. Young said that all of the relevant studies, including ICON3,
were well designed and had good total patient numbers. So
its unclear why ICON3s control subjects did better,
He concluded that, despite the ICON3 results, for previously
untreated advanced ovarian cancer with substantial residual disease,
the treatment of choice should be Taxol/carboplatin. . . . For
patients with limited or no residual disease, again I would select
Taxol/carboplatin. He said that the optimal dose remains to be