NO BENEFIT OF ADDING A THIRD DRUG

Additional Chemo Agent No Benefit in Advanced-Stage Ovarian Cancer

NEW YORK (Reuters Health) Mar 13 - The addition of a third cytotoxic agent to a standard treatment regimen of paclitaxel and carboplatin does nothing to improve overall or progression-free survival in women with advanced epithelial ovarian carcinoma, according to a multinational phase III trial published ahead of print on February 17 by the Journal of Clinical Oncology.

"The possible addition of a third cytotoxic drug to a core regimen of carboplatin and paclitaxel was an objective shared by multiple international phase III trials over the last 10 years," Dr. Michael A. Bookman of the Fox Chase Cancer Center, Philadelphia, told Reuters Health. "Although the hypothesis was based on good preclinical data ... none of the phase III trials have shown an advantage for adding a third drug."

"However," he added, "all of these drugs continue to have a potential role in the management of recurrent disease, either alone, or in combination with carboplatin, depending on the timeframe of recurrence."

The current study enrolled 4312 women over a period of 3.5 years. Participants had a confirmed histologic diagnosis of epithelial ovarian carcinoma or primary peritoneal carcinoma, stage III or IV, and had either optimal or suboptimal residual disease following cytoreductive (debulking) surgery.

The subjects were randomized to a reference arm, which received paclitaxel and carboplatin only, or one of four experimental arms in which a third agent was added to standard therapy. There were two gemcitabine arms, a topotecan arm and a liposomal doxorubicin arm. Nearly 80% of the women completed 8 cycles of the assigned therapy.

A prespecified interim analysis was triggered by a combination of total progressions and deaths among the participants. The researchers found no statistically significant difference in either progression-free or overall survival associated with any of the four experimental regimens, versus 8 cycles of carboplatin and paclitaxel.

While noting the efficiency of the multiarm trial design, the researchers conclude: "The development of new interventions beyond surgery and conventional platinum-based chemotherapy is required to additionally improve outcomes of women with advanced epithelial ovarian carcinoma."