At this time, we have no evidence for superiority of an intraperitoneal regimen using reduced doses of cisplatin and 3-hour paclitaxel, and we may not get it from future trials.
—Gini Fleming, MD
In the discussion session, Gini Fleming, MD, Professor of Medicine and Director of the Gynecologic Oncology and Medical Oncology Breast Program at the University of Chicago Medical Center, analyzed the three previous, large trials on which the presumed benefits of intraperitoneal therapy in women with optimally debulked ovarian cancer were based: SWOG 8501, GOG 114, and GOG 172. Although all the intraperitoneal regimens differed slightly, as did the intravenous controls, they had one thing in common, said Dr. Fleming: They all used intraperitoneal cisplatin at 100 mg/m2.
With only one variable, the route of administration of cisplatin, the SWOG study was the “cleanest of the trials for interpretation,” said Dr. Fleming. That trial, like the rest, showed a clear overall survival benefit. She also noted that the most recent trial, GOG 172, showed a very dramatic 16- to 17-month survival benefit—far better than anything currently promised for ovarian cancer by newer, targeted agents.
“Unfortunately,” said Dr. Fleming, “the results of Dr. Walker’s trial show no difference between the three arms but significantly more toxicity, including nausea and vomiting, with intraperitoneal cisplatin.”
Dr. Fleming offered two possible explanations for the disappointing results: (1) The reduced dose of platinum in the intraperitoneal arm and the increased dose of the paclitaxel in the control arm leave little difference between the dose-modified intraperitoneal cisplatin and the dose-dense paclitaxel-carboplatin control; (2) as Dr. Walker suggested, there’s some effect of bevacizumab, which obscures differences between arms based on dose intensity.
“In conclusion, I think we’re stuck,” said Dr. Fleming. “At this time, we have no evidence for superiority of an intraperitoneal regimen using reduced doses of cisplatin and 3-hour paclitaxel, and we may not get it from future trials. The intraperitoneal cisplatin regimen in GOG 252 is already more toxic, and we’re not likely to return to using 100 mg/m2 of intraperitoneal cisplatin.”
Based on the SWOG trial, added Dr. Fleming, there is likely a benefit to intraperitoneal cisplatin over intravenous cisplatin at the same dose, but the magnitude of the benefit is probably less than that seen in GOG 172. And, whether or not the toxicities will be tolerable when more paclitaxel is added is very uncertain, she concluded. ■
Disclosure: This clinical trial was supported by Genentech for bevacizumab and drug distribution. Dr. Fleming reported no potential conflicts of interest.
A phase III trial of bevacizumab (Avastin) with intravenous vs intraperitoneal chemotherapy showed no improvement in progression-free survival for first-line treatment of patients with optimally surgically resected stage II and III ovarian, peritoneal, or fallopian tube cancer.1 When compared with...