SAN DIEGOData from a major randomized phase III trial show that
carboplatin (Paraplatin)/paclitaxel (Taxol) should replace cisplatin
(Platinol)/paclitaxel as standard treatment for optimal stage III
ovarian cancer, Robert F. Ozols, MD, PhD, said at the Society of
Gynecologic Oncologists 31st Annual Meeting.
We do not have to use cisplatin and do not have to hospitalize
these patients, Dr. Ozols told ONI. Carboplatin/paclitaxel
is easier, less toxic, and as effective as cisplatin/paclitaxel, as
was shown in phase I and phase II trials. Our data show that the
regimen of carboplatin with 3-hour paclitaxel infusion is as
effective as the gold standard regimen of cisplatin with
24-hour paclitaxel. Dr. Ozols is professor of medical oncology,
Fox Chase Cancer Center.
This trial, Gynecologic Oncology Group (GOG) 158, included 840
patients, 798 of whom were evaluable. All patients had optimal stage
III epithelial ovarian cancer with no residual tumor nodules larger
than 1 cm. Sixty-three percent of patients had gross residual
disease, and 37% were without gross residual disease.
This trial was designed to answer the question of whether
carboplatin/paclitaxel is equivalent to cisplatin/paclitaxel. [See Table
for dosages.] The two clinical concerns were that carboplatin might
not be as effective as cisplatin and that the 3-hour paclitaxel
infusion might not be as effective as a 24-hour infusion, Dr.
The study was designed to address both of these questions and also
included a nonrandomized prospective comparison of relapse-free
survival and overall survival in patients who either had second-look
surgery or who were followed clinically after initial chemotherapy.
At the time patients were randomized for chemotherapy, they
registered for second-look surgery (392 patients) or for no
second-look surgery (403 patients). Fifty-nine patients (15%)
registered to second-look surgery refused, the surgery was medically
contraindicated in another 5 patients (1%), and 34 (9%) had disease
progression prior to their scheduled surgery.
At a median follow-up of 24 months, median relapse-free survival was
21.7 months with cisplatin/paclitaxel and 22.0 months with
carboplatin/paclitaxel. Dr. Ozols reported that the relative risk for
progression was decreased to 0.91 (CI: 0.76 to 1.10) for
carboplatin/paclitaxel, compared with cisplatin/paclitaxel, with or
without adjusting for prognostic factors. Overall survival analysis
is not yet available.
Relapse-free survival rates did not vary for patients registered for
second-look surgery, compared with those who were not registered for
surgery. The frequency of negative second-look surgery was 45.2% for
cisplatin/paclitaxel and 51.5% for carboplatin/paclitaxel.
The cisplatin/paclitaxel regimen was associated with significantly
more serious toxicity (Table 2).
There is no question that carboplatin/paclitaxel is preferable.
It is less toxic, easier to give, has fewer adverse effects, and
appears to be at least equivalent to cisplatin/paclitaxel in efficacy
in these patients, Dr. Ozols said.
Dr. Ozols said that the conclusions from the second-look-surgery data
must be viewed cautiously because patients were not randomized.
Within those constraints, the GOG 158 data do not suggest an
advantage to second-look surgery in management of optimal stage III
ovarian cancer. If the patient does have positive second-look
surgery, treatment at that point is not likely to influence
relapse-free survival, Dr. Ozols said. There is no
evidence that you need to do second-look surgery. This trial was not
randomized, but it is the largest prospective study available.