SAN DIEGO—Data from a major randomized phase III trial show that carboplatin(Drug information on carboplatin) (Paraplatin)/paclitaxel (Taxol) should replace cisplatin(Drug information on 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(Drug information on 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. Ozols said.
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.
Study Results
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.”
