Intraperitoneal Regimen Boosts Survival in Phase III Ovarian Cancer Clinical Trial

BALTIMORE—Giving paclitaxel (Taxol) and cisplatin (Platinol) in an intensive intraperitoneal (IP) regimen increased progression-free survival by 5 months over standard intravenous (IV) treatment for stage III epithelial ovarian carcinoma and primary peritoneal carcinoma in a phase III clinical trial (ASCO abstract 803).

Deborah K. Armstrong, MD, of the Sidney Kimmel Comprehensive Cancer Center at the Johns Hopkins University School of Medicine presented the preliminary results from Gynecologic Oncology Group (GOG) trial 172. "This is the third randomized clinical trial to show a clinical benefit for the use of IP therapy in patients with optimally debulked ovarian cancer," she said. "Survival outcomes from this study will be key in determining the role of intensive IP therapy in future clinical trials and as part of standard treatment for optimally debulked ovarian cancer."

Median overall progression-free survival was 24.3 months for 205 women who were in the IP arm compared to 19.3 months for 211 women who received standard IV therapy. In the IP arm, more women were progression free (112) than had failed treatment (93). Conversely, in the IV arm, more women failed therapy (115) than were progression free (96).

For patients with gross residual disease, Dr. Armstrong reported the median progression-free survival was 20.7 months with IP therapy, compared to 15.7 months on the IV arm. Previous studies have also shown a 5-month gain from the intensive treatment, she said.

Prognostic Factors

Not enough events have occurred to reach a median in overall survival, according to Dr. Armstrong. At the time of her presentation, she reported that 61 IV patients and 46 IP patients had died. The study identified the following factors as being associated with a worse prognosis for patients in the study:

• gross residual disease;

• mucinous and clear cell histologies; and

• increasing age, starting at 45 years.

Each woman in the trial had a newly diagnosed tumor that was reduced surgically to 1 cm in diameter or less no more than 6 weeks before starting chemotherapy. Nearly two-thirds of the women in both arms had gross residual disease that was visible at the end of initial surgery.

One group received the standard regimen of IV paclitaxel (135 mg/m²/24h) followed by IV cisplatin (75 mg/m²). The other was given IV paclitaxel (135 mg/m²/24h) followed by IP cisplatin (100 mg/m²); IP paclitaxel (60 mg/m²) was given on the eighth day of each 21-day cycle (see Figure 1).

Pronounced Toxicities

Hematologic and nonhematologic toxicities were more pronounced in the IP arm (see Table 1), according to Dr. Armstrong. The women who received IP therapy had more grade 4 leukopenia, 31% vs 14% for women who received IV therapy. Those in the IP arm also had more grade 3/4 toxicities. Fewer patients in the IP arm (81% vs 87%) completed all six cycles of therapy.

"My feeling is a lot of us have forgotten how to manage cisplatin-based toxicity," Dr. Armstrong said, adding that many complications were related to catheter use. "We didn’t prescribe the type of catheter to be used," she said. "One of the things we would like to look at was which catheters were associated with fewer complications." Another question to be explored, she added, was whether institutions that do a lot of IP therapy have fewer complications.

IP as Standard of Care?

These early results raise questions about why IP hasn’t been adopted as standard therapy, remarked Elizabeth A. Eisenhauer, MD, of Queens University in Kingston, Ontario, Canada. She suggested there is a prevailing belief against IP treatment because it is more toxic and complicated than standard therapy. "The technical expertise with which it’s done has been a bit lost in this particular generation. It isn’t as popular. People aren’t as trained to do it as frequently as they were 10 to 15 years ago," she said.

"But if GOG 172 again shows there is a significant survival difference, we shouldn’t dismiss it so readily," Dr. Eisenhauer concluded, "and we should consider this approach in future studies or perhaps for the standard care for this group of patients."