NEW YORK (Reuters Health) - Weekly paclitaxel, compared with every-three-week paclitaxel, did not prolong progression-free survival (PFS) in women with ovarian cancer, but a subset of patients did show improvement.
Dr. John Chan, of the California Pacific-Palo Alto Medical Foundation, Sutter Cancer Research Institute, San Francisco, and colleagues conducted a phase 3 open-label randomized trial comparing weekly paclitaxel and carboplatin treatment with every-three-week paclitaxel and carboplatin. All patients were also offered the option of receiving bevacizumab (Avastin, Genentech) in addition to each regimen, and 84% chose to do so.
The weekly paclitaxel regimen did not significantly improve PFS over every-three-week paclitaxel - except in the subgroup of women who opted out of bevacizumab.
"We believe that the effect of the Avastin neutralized the effect of weekly paclitaxel," Dr. Chan told Reuters Health in a telephone interview. "If you look at the subgroup of patients who did not get (bevacizumab), weekly paclitaxel was beneficial. In fact, it had a 38% improvement in our cohort in progressive-free survival."
Dr. Chan and colleagues enrolled 692 patients between September 2010 and February 2012 at more than 200 clinics in the U.S., Canada, and South Korea. Most patients (85%) were non-Hispanic white, according to an article online February 25 in the New England Journal of Medicine.
The every-three-week patients received paclitaxel 175 mg/m2 IV over three hours on day 1 of a 21-day cycle for six cycles, plus carboplatin. The weekly patients received 80 mg/m2 IV over one hour on days 1, 8, and 15 of a 21-day cycle for six cycles, plus carboplatin. Patients opting for bevacizumab received 15 mg/kg every 21 days beginning at the second cycle and continuing until the disease progressed or an adverse event precluded therapy.
Eighty-eight (13%) patients also had neoadjuvant chemotherapy and interval cytoreductive surgery.
Researchers assessed disease status using computed tomography or magnetic resonance imaging prior to treatment initiation and after chemotherapy cycles 3 and 6. After chemotherapy stopped, they repeated measurements periodically.
Two-thirds (67%) of the patients were alive after a median follow-up of 28 months. The researchers found that weekly paclitaxel led to 14.7 months PFS compared to 14.0 months for the every-three-week regimen (hazard ratio for death or progression 0.89, p=0.18). However, for patients who opted not to receive bevacizumab, weekly paclitaxel led to 3.9 months longer PFS (14.2 months versus 10.3 months, HR 0.62, p=0.03).
"I still think that this weekly paclitaxel is an active and promising regimen for upfront treatment of ovarian cancer," he continued. "Also weekly paclitaxel had a better toxicity profile. It was less toxic on the white blood cells, more specifically the neutrophils. It does not hurt the immune system as much as the every-three-week regimen, but it did give slightly more grade 2 neuropathy."
"Our study suggests that the new alternative strategy should be either weekly paclitaxel without bevacizumab or every-three-week paclitaxel with bevacizumab, but it shouldn't be every-three-week paclitaxel alone," Dr. Chan said.
He said the choice of regimen should be based on toxicity profiles, patient convenience, and economics.
"Although paclitaxel and carboplatin administered every three weeks and combined with bevacizumab may be more convenient than weekly paclitaxel and carboplatin without bevacizumab, the every-three-week regimen is also associated with higher costs, with an incremental cost-effectiveness ratio as calculated by others of $401,088 versus $5,809 per progression-free life-year saved," Dr. Chan and colleagues wrote.
The National Cancer Institute and Genentech funded this research. Three coauthors reported disclosures.
SOURCE: http://bit.ly/1Lg9vG6
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