Dose-dense paclitaxel failed to prolong progression-free survival beyond that achieved with standard paclitaxel in an international phase III clinical trial involving 692 women with newly diagnosed advanced ovarian cancer, according to a study published online online Feb. 25 in the New England Journal of Medicine.
Dose-dense paclitaxel involves a greater frequency of infusions – weekly vs. every 3 weeks – which is thought to enhance the agent’s antineoplastic effect by facilitating intratumoral perfusion to inhibit angiogenesis. In a recent trial in Japan, this approach was associated with longer overall survival in women with ovarian cancer, compared with conventional paclitaxel dosing, said Dr. John K. Chan of the California Pacific–Palo Alto Medical Foundation, Sutter Cancer Research Institute, San Francisco, and his associates.
They compared the two approaches in an open-label trial involving women with newly diagnosed, untreated, incompletely resected stage III or stage IV epithelial ovarian, fallopian tube, or peritoneal cancer. These patients were treated at 209 clinics in the United States, Canada, and South Korea and followed for a median of 28 months.
Dose-dense paclitaxel didn’t prolong progression-free survival (PFS) compared with conventional paclitaxel (14.7 vs 14.0 months, respectively) in the intention-to-treat analysis or a sensitivity analysis. Moreover, “the effect of the paclitaxel regimen on progression-free survival did not differ significantly between patients who were left with microscopic residual disease and those who were left with macroscopic residual disease, nor did it differ significantly between those who had neoadjuvant chemotherapy followed by interval cytoreduction and those who received primary cytoreduction,” the investigators said.
However, in the subgroup of 112 patients who chose not to receive optional bevacizumab, dose-dense paclitaxel was associated with significantly longer PFS (14.2 months) than was conventional paclitaxel (10.3 months), for an HR of 0.62 (N Engl J Med. 2016 Feb 25. doi: 10.1056/NEJMoa1505067).
Patients who received dose-dense paclitaxel reported poorer quality of life. In particular, severe neuropathy was more frequent among those receiving paclitaxel every week (26%) rather than every 3 weeks (18%). The most common serious adverse events were neutropenia, gastrointestinal disorders (including GI-wall perforation, fistula, or necrosis), thrombocytopenia, infection, and anemia. Severe anemia was more common with weekly paclitaxel, but severe neutropenia was less common in that group.