At the 37th annual meeting of the American Society of Clinical Oncology, investigators from the Scottish Gynaecologic Cancer Trials Group reported that the combination of docetaxel(Drug information on docetaxel) (Taxotere) and carboplatin(Drug information on carboplatin) (Paraplatin) appears to be equally effective and less toxic than the combination of paclitaxel(Drug information on paclitaxel) (Taxol) and carboplatin when used as first-line therapy in patients with advanced ovarian cancer. The paclitaxel/carboplatin combination is currently standard treatment for this disease.
Early results from the phase III Scottish Randomized Trial in Ovarian Cancer (SCOTROC) showed that the two treatments had similar 1-year progression-free survival results. However, women treated with the docetaxel/carboplatin combination had significantly less neurotoxicity than women randomized to the paclitaxel/carboplatin combination.
"While significant progress has been made over the last 2 decades in the management of gynecologic cancers, the overall 5-year survival rate for these patients is still less than 30%," said Dr. Paul A. Vasey, lead investigator of the trial and medical oncologist at the Cancer Research Campaign Clinical Trials Unit at Beatson Oncology Centre of the Western Infirmary in Glasgow. "Our finding that the docetaxel/carboplatin combination appears to be as effective but better tolerated with respect to neurotoxicity than the current standard may represent an important advance for this patient population," said Dr. Vasey, who presented the data.
Eligibility Criteria and Protocol
The study included 1,077 women with a histologically confirmed diagnosis of ovarian cancer who had not received prior chemotherapy for their malignancy. Patients with peritoneal carcinoma were also eligible, because this type of cancer is generally considered to be identical to ovarian cancer with respect to the cell of origin, prognosis, and response to chemotherapy. All study participants were at least 18 years old and had a performance status of 0 to 2.
The two treatment groups were similar in terms of known prognostic factors. Following surgical removal of their tumor, patients were randomized to receive docetaxel at 75 mg/m2 administered intravenously (IV) over 1 hour, or paclitaxel at 175 mg/m2 IV over 3 hours, in combination with carboplatin IV at an area under the concentration-time curve (AUC) of 5 over 30 minutes. Treatments were repeated six times at 3-week intervals.
The docetaxel/carboplatin and paclitaxel/carboplatin groups had similar response rates. Of 297 patients treated with docetaxel/carboplatin, 29% achieved a complete response and 36% had a partial response, for an overall response rate of 65%. Among patients who received paclitaxel/carboplatin, 29% had a complete response and 33% had a partial response, for an overall response rate of 62%. A significant decrease in serum CA-125 was noted in 75% of the patients in the docetaxel/carboplatin cohort and 76% of those in the paclitaxel/carboplatin cohort.
Toxicity Profile Significantly Better
Overall, 1,077 patients were evaluable for toxicity. Clinically significant neuropathy developed in 30% of women treated with paclitaxel/carboplatin (National Cancer Institute of Canada Common Toxicity Criteria [NCIC-CTC] grade 2/3) vs 11% of those treated with docetaxel/carboplatina statistically significant difference. In addition, after six treatment cycles, almost 80% of patients receiving paclitaxel/carboplatin had neuropathic symptoms compared with only 40% of those receiving docetaxel/carboplatin. "These data clearly show that the docetaxel/carboplatin regimen produces significantly less neurotoxicity than the current treatment standard," said Dr. Vasey.
Significant neutropenia (grade 3/4) occurred in 95% of the docetaxel/carboplatin arm and 82% of the paclitaxel/carboplatin arm. Dr. Vasey said that the neutropenia associated with the docetaxel/carboplatin regimen was easily managed, and there were no excess treatment-related deaths.
Analyses are ongoing to examine quality of life and duration to further determine the survival end points for the two treatment arms. Participants in the SCOTROC trial were drawn from 83 medical centers in 10 countries.