David Brill
The efficacy of a weekly dosing regimen of paclitaxel as an adjuvant therapy for breast cancer has been confirmed by a large-scale trial published in the New England Journal of Medicine.
The researchers found that diseasefree survival rates were higher among patients who took weekly paclitaxel than among those who adhered to other taxane dosing schedules following a standard anthracyline regimen of doxorubicin and cyclophosphamide.
Compared to those who took the drug every 3 weeks, the odds ratios for disease-free survival were 1.27 for weekly paclitaxel (P=.006), 1.23 for 3-weekly docetaxel (P=.02) and 1.09 for weekly docetaxel (P=.29). Overall survival rates were also higher for patients who took paclitaxel weekly, compared to those who took the drug every 3 weeks (odds ratio 1.32; P=.01). [N Engl J Med 2008 Apr 17;358(16):1663-71]
“I think it’s an important paper,” said Dr. Zee Wan Wong, a consultant at Singapore’s National Cancer Centre.
“It reinforces the fact that paclitaxel … actually does add to the benefit that patients derive from adjuvant chemotherapy with anthracyclines.”
The efficacy of paclitaxel as an adjuvant breast cancer therapy has been known for several years but the drug has typically been administered every 3 weeks. Preliminary data from the trial, presented in 2005, had hinted at the superiority of weekly dosing but the results were not statistically significant at that time.
In light of the available evidence, however, many centers have already begun to change their dosing practices, according to Wong.
“It’s quite reassuring to know that we have been giving our patients the right treatment,” she said, following the publication of the complete data from the trial.
The study, which comprised 4,950 participants, also demonstrated that among patients with human epidermal growth factor receptor type 2 (HER2)-negative cancer, the benefits of weekly paclitaxel extended to patients with hormone receptor-negative and those with hormone receptor-positive disease. Previous studies had suggested that taxane therapy might be of little benefit to those with the latter disease type.
A weekly schedule of paclitaxel appears, however, to have the least favorable toxicity profile of the dosing regimens investigated in the trial. The incidence of grade 2, 3 or 4 neuropathy among patients in this group was 27 percent – significantly higher than in the other treatment arms
(P<.001).
Wong added that, although these effects are largely reversible following cessation of treatment, weekly paclitaxel should be used with caution in patients who have comorbidities that could predispose them to neuropathy, such as those with poorly-controlled diabetes.
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