Currently, there is no clear standard of care for patients with relapsed ovarian cancer. These women are not curable. However, oncologists would like to have a treatment that will extend overall survival and disease free survival. One such regimen could be the combination of paclitaxel and platinum-based chemotherapy.

Two parallel trials were undertaken to evaluate a randomized comparison of paclitaxel-platinum combination chemotherapy versus conventional platinum-based chemotherapy in relapsed ovarian cancer. One trial is the International Collaborative Ovarian Neoplasm 4 (ICON 4) Trial from centers in the United Kingdom and Italy. The second is a smaller, similar trial from the German group Arbeitsgemeinschaft Gynaekologische Onkologie (AGO).

Here at ASCO, Dr. Ledermann showed the prospective analysis of these 2 parallel trials. With a total enrollment of 802 patients, this investigation is the largest randomized trial ever in relapsed ovarian cancer.

The trial was open to patients who had relapsed ovarian cancer or primary peritoneal (serous type) carcinoma. Entry criteria included platinum-based chemotherapy for at least 6 cycles prior to study entry (at least 12 cycles for the Italian group).

Investigators from centers in the U.K., Italy, Norway, Germany and Switzerland randomized patients to conventional platinum-based chemotherapy with carboplatin or cisplatin, or to paclitaxel plus carboplatin or cisplatin. The regimens were as follows:

Pre-treatment patient characteristics were well balanced across the 2 arms. The median age was approximately 60, and 94% had performance scores of 0 or 1. More than 70% of the women had a treatment-free interval of more than 12 months. About 40% of patients had previously received platinum plus a taxane as first-line treatment. Others received either single-agent platinum (usually carboplatin) or another platinum-based regimen.

There was a higher incidence of neurotoxicity in the paclitaxel-platinum arm: 20%, versus approximately 1% in the control arm. In addition an 86% incidence of alopecia was seen in the combination arm compared with 25% in the standard platinum-based chemotherapy arm. Interestingly, there did appear to be a lower incidence of hematologic toxicity in the combination arm (29% versus 46%). Other toxicities were not noted to be significantly different between the two arms.

As of this report, investigators had followed the patients for a median of 42 months. The results show that the combination chemotherapy arm provides a significant survival advantage. At two years, survival increased from 50% to 57%, or an absolute difference in survival of 7%.

There was also a significant increase in progression-free survival favoring the paclitaxel plus platinum arm. At 1 year, the absolute difference in progression-free survival was 10%.

Investigators also conducted exploratory subgroup analysis. The purpose was to determine if there were any patient factors that had a beneficial or detrimental effect on the survival advantage. These variables included time since completion of last chemotherapy, previous exposure to taxanes, age and WHO performance status.

In every case, the exploratory subgroup analysis showed no detrimental or beneficial effect of any variable. For example, previous treatment with a taxane did not seem to adversely affect the benefit of paclitaxel and platinum. Likewise, a treatment-free interval of less than 12 months did not seem to affect survival unfavorably.

Dr. Ledermann concluded that combination chemotherapy provides a survival and progression-free survival advantage in patients with relapsed ovarian cancer. This effect is not influenced by prior treatment with taxanes or treatment-free interval of less than 12 months.