Lower doses might improve drug delivery, while higher doses can impede drug delivery and increase metastasis
San Francisco, CA (PRWEB) February 21, 2016
A new approach to treating ovarian cancer provides similar benefits with less toxicity compared to a standard taxane-based chemotherapy dosing regimen, according to results published online today in the The New England Journal of Medicine.
The open-label, phase 3 randomized study was conducted by researchers at Sutter Health’s California Pacific Medical Center (CPMC) and leading cancer centers across the U.S., and suggests new strategies for personalized treatments.
Encouraging clinical results from previous studies showed improved survival with a ‘dose dense’ administration of the chemotherapy drug paclitaxel, and increased progression-free survival (PFS) with the addition of the monoclonal (or, ‘biologic’) antibody bevacizumab (Avastin®). The findings prompted lead study author John Chan, MD, scientist and gynecologic oncologist at CPMC and colleagues to determine if less frequent dosing of paclitaxel could provide the same PFS benefits. Dose-dense therapy is based on the hypothesis that a frequent interval of the doses of cytotoxic agents will kill cancer cells more effectively.
“No previous studies assessed the weekly administration of paclitaxel with bevacizumab, to target angiogenesis,” said Dr. Chan. “Moreover, there has been little research into how taxanes may have differing effects depending on the concurrent administration of bevacizumab.”
In the study, 692 women with newly diagnosed stage II-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer who had received no prior treatment were prospectively stratified by whether they elected to receive bevacizumab, and then randomly allocated to receive either paclitaxel every three weeks plus carboplatin, or weekly paclitaxel plus carboplatin. The primary study endpoint was PFS.
After a median follow-up of 28 months, weekly paclitaxel did not significantly prolong PFS, over its administration every three weeks in the overall intent-to-treat group (14.7 versus 14 months respectively; p=0.18). Of those who did not receive bevacizumab (16% of the total group of patients), weekly paclitaxel was associated with an almost four-month improvement in PFS over giving the chemotherapy every three weeks (14.2 vs. 10.3 months; p=0.03). But in patients who received bevacizumab (85% of the study group), weekly paclitaxel did not prolong PFS over dosing every three weeks (14.9 vs. 14.7 months; p=0.6).
Weekly paclitaxel resulted in more grade 3-4 anemia (36.5% vs. 15.7%) and more grade 2-4 sensory neuropathy (25.9% vs. 17.8%) but less grade 3-4 neutropenia (72.3% vs. 83.4%), compared with its administration every three weeks.
“We suspect that the dose of an anti-vascular drug such as paclitaxel may affect tumor vascular normalization: lower doses might improve drug delivery, while higher doses can impede drug delivery and increase metastasis,” said Dr. Chan. “Clearly, the dosing of taxanes including paclitaxel combined with biologic therapy warrants further investigation, including comparative effectiveness studies with consideration of cost,” said Dr. Chan.
Approximately 21,000 American women are diagnosed with ovarian cancer every year, and about 67% of them will eventually die from the illness (American Cancer Society).
The study was supported by the National Cancer Institute and Genentech.