UAB was a lead enrollment site for the clinical trial that evaluated dosage of the chemotherapy drug paclitaxel. The Study showed that a weekly dose versus an every three week dose failed to improve progression-free survival (PFS) in patients with advanced ovarian cancer compared to a conventional regimen and optional bevacizumab (Avastin). Previous studies show that incorporating bevacizumab, which slows the growth of new blood vessels, into the treatment with paclitaxel prolongs PFS but not overall survival.
Eligible patients had newly diagnosed, untreated, incompletely resected stage III ovarian cancer or any stage IV disease. Criteria were later modified to include patients with stage II or III disease with no residual lesions larger than one centimeter.
The multinational study, published in the February 25 issue of the New England Journal of Medicine, was conducted in the United States, Canada and South Korea to confirm the outcome of a Japanese Gynecologic Oncology Group study that saw a substantial benefit in the weekly dosage of paclitaxel. “There are distinct differences in ovarian cancers in Japan and in the United States, and we felt we needed to confirm that result,” says Warner Huh, MD, director of the UAB Division of Gynecologic Oncology and senior scientist at the UAB Comprehensive Cancer Center.
UAB investigators looked at the combined dose-dense weekly paclitaxel with bevacizumab, and overall results showed that a regimen of weekly paclitaxel did not prolong PFS as compared with the three-week treatment regimen. Results also showed that patients who did not receive bevacizumab with the weekly dose of paclitaxel saw a PFS that was 3.9 months longer than those who received paclitaxel every three weeks.
“We didn’t see a clinical benefit with the weekly paclitaxel like the Japanese did, but there is a distinct possibility that the bevacizumab negated the effect since both drugs are anti-angiogenesis agents,” Huh says. “What’s interesting is that 16 percent of the 692 patients in the trial who received weekly paclitaxel but didn’t get bevacizumab may have had a clinical benefit, but the group was too small for a sound scientific conclusion.”
More information could come from another trial that randomized patients with ovarian cancer to dose-dense chemotherapy versus two different intraperitoneal (IP) and intravenous (IV) chemotherapy regimens. All patients received bevacizumab.
“Depending on how much cancer remains following surgery, ovarian cancer patients have the option to receive IV or IP/IV chemotherapy. This study could suggest that there may not be a difference between IV and IP chemotherapy. As a result, if you look at all of this in the aggregate, it is possible that IP/IV chemotherapy may fall out of favor and weekly chemotherapy may become the preferred regimen,” Huh says. “The bottom line is these studies suggest that there might be some value to using weekly paclitaxel. Giving chemotherapy weekly still is not unreasonable, but we definitely won’t be giving it with bevacizumab, which we don’t do anyway.”
