Docetaxel/Carboplatin Combination Produces Impressive Response in Ovarian Cancer Patients

July 1, 2001

At the 37th annual meeting of the American Society of Clinical Oncology, investigators from the Scottish Gynaecologic

At the 37th annual meeting of the AmericanSociety of Clinical Oncology, investigatorsfrom the Scottish Gynaecologic Cancer Trials Group reported that the combinationof docetaxel (Taxotere) and carboplatin (Paraplatin) appears to be equallyeffective and less toxic than the combination of paclitaxel (Taxol) andcarboplatin when used as first-line therapy in patients with advanced ovariancancer. The paclitaxel/carboplatin combination is currently standard treatmentfor this disease.

Early results from the phase III Scottish Randomized Trial inOvarian Cancer (SCOTROC) showed that the two treatments had similar 1-yearprogression-free survival results. However, women treated with thedocetaxel/carboplatin combination had significantly less neurotoxicity thanwomen randomized to the paclitaxel/carboplatin combination.

"While significant progress has been made over the last 2decades in the management of gynecologic cancers, the overall 5-year survivalrate for these patients is still less than 30%," said Dr. Paul A. Vasey,lead investigator of the trial and medical oncologist at the Cancer ResearchCampaign Clinical Trials Unit at Beatson Oncology Centre of the WesternInfirmary in Glasgow. "Our finding that the docetaxel/carboplatincombination appears to be as effective but better tolerated with respect toneurotoxicity than the current standard may represent an important advance forthis patient population," said Dr. Vasey, who presented the data.

Eligibility Criteria and Protocol

The study included 1,077 women with a histologically confirmeddiagnosis of ovarian cancer who had not received prior chemotherapy for theirmalignancy. Patients with peritoneal carcinoma were also eligible, because thistype of cancer is generally considered to be identical to ovarian cancer withrespect to the cell of origin, prognosis, and response to chemotherapy. Allstudy participants were at least 18 years old and had a performance status of 0to 2.

The two treatment groups were similar in terms of knownprognostic factors. Following surgical removal of their tumor, patients wererandomized to receive docetaxel at 75 mg/m2 administered intravenously (IV) over1 hour, or paclitaxel at 175 mg/m2 IV over 3 hours, in combination withcarboplatin IV at an area under the concentration-time curve (AUC) of 5 over 30minutes. Treatments were repeated six times at 3-week intervals.

The docetaxel/carboplatin and paclitaxel/carboplatin groups hadsimilar response rates. Of 297 patients treated with docetaxel/carboplatin, 29%achieved a complete response and 36% had a partial response, for an overallresponse rate of 65%. Among patients who received paclitaxel/carboplatin, 29%had a complete response and 33% had a partial response, for an overall responserate of 62%. A significant decrease in serum CA-125 was noted in 75% of thepatients in the docetaxel/carboplatin cohort and 76% of those in thepaclitaxel/carboplatin cohort.

Toxicity Profile Significantly Better

Overall, 1,077 patients were evaluable for toxicity. Clinicallysignificant neuropathy developed in 30% of women treated withpaclitaxel/carboplatin (National Cancer Institute of Canada Common ToxicityCriteria [NCIC-CTC] grade 2/3) vs 11% of those treated withdocetaxel/carboplatin—a statistically significant difference. In addition,after six treatment cycles, almost 80% of patients receivingpaclitaxel/carboplatin had neuropathic symptoms compared with only 40% of thosereceiving docetaxel/carboplatin. "These data clearly show that thedocetaxel/carboplatin regimen produces significantly less neurotoxicity than thecurrent treatment standard," said Dr. Vasey.

Significant neutropenia (grade 3/4) occurred in 95% of thedocetaxel/carboplatin arm and 82% of the paclitaxel/carboplatin arm. Dr. Vaseysaid that the neutropenia associated with the docetaxel/carboplatin regimen waseasily managed, and there were no excess treatment-related deaths.

Analyses are ongoing to examine quality of life and duration tofurther determine the survival end points for the two treatment arms.Participants in the SCOTROC trial were drawn from 83 medical centers in 10countries.