Katsumata and colleagues showed a better long-term progression-free survival (PFS) and overall survival for dose-dense paclitaxel and carboplatin treatment versus the standard first-line treatment in patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancers.1
However, the interpretation of these findings needs several considerations.
The concept of dose-dense therapy is based on the Gompertzian model, and is achieved by increasing the administration frequency of the chemotherapeutic drug without affecting the total cumulative dose, thereby decreasing the chance for regrowth of cancer cells between treatment cycles.2
Katsumata and colleagues stated that patients in the control group received 180 mg/m2
paclitaxel every 3 weeks for at least six cycles, whereas patients in the dose-dense group were given 80 mg/m2
paclitaxel on day 1, 8, and 15, for six cycles, which indicates that patients in the dose-dense group received at least 360 mg/m2
more paclitaxel at the end of six cycles of chemotherapy than did controls. Hence, we could conclude that each patient in the dose-dense group was given an additional dose—which corresponds to two more cycles of chemotherapy—than patients in the control group received. Moreover, it is clear from the article that patients with measurable partial or complete responses received three additional cycles of chemotherapy, which means that responsive patients in the dose-dense group received an additional dose of 180 mg/m2
, which corresponds to an additional cycle. Therefore, the regimen given according to the study protocol appears not to fit into the dose-dense concept, and the cumulative dose that patients in the control group received was far lower than that received by the study group.
Angiogenesis has an important role in the development of epithelial ovarian cancers, and paclitaxel was previously reported to inhibit angiogenesis.3
Furthermore, VEGF concentrations in patients with breast cancer who are responding well to weekly paclitaxel were shown to decrease significantly after treatment for 12 weeks.5
Therefore, the antiangiogenic effect of weekly paclitaxel should not be ignored as a potential cause of the improvement noted in long-term PFS and overall survival in the JGOG 3016 study. As more disease-specific biology is revealed and novel targeted therapeutic drugs are developed, more phase 3 trials with large sample sizes will be needed to identify the optimum dose schedule and combination of paclitaxel with novel anticancer therapeutics.
We declare that we have no conflicts of interest.