Randomized Phase III Trial of Weekly Compared With Every-3-Weeks Paclitaxel for Metastatic Breast Cancer, With Trastuzumab for all HER-2 Overexpressors and Random Assignment to Trastuzumab or Not in HER-2 Nonoverexpressors: Final Results of Cancer and Leukemia Group B Protocol 9840

Abstract

Weekly paclitaxel is more effective than every-3-weeks administration for MBC. Trastuzumab did not improve efficacy for HER-2 nonoverexpressors. Neurotoxicity is a treatment-limiting toxicity for weekly paclitaxel.

Polymorphisms in cytochromes P450 2C8 and 3A5 are associated with paclitaxel neurotoxicity

“…As paclitaxel neurotoxicity is dose-dependent, 13 we calculated the accumulated paclitaxel dose that produced clinically relevant neurotoxicity, rather than just evaluating the presence or lack of neurotoxicity at the end of the treatment. We confirmed that the more dose intense paclitaxel schedule of 80-90 mg m À2 weekly was a risk factor for the neurotoxicity 8,9 and, although previous results concerning age are inconclusive, 12,13,40 we found that patients below 50 years developed greater neuropathy (Supplementary Figure 1).…”

“…6,7 Neurotoxicity, which has become the dose-limiting toxicity of paclitaxel, exhibits substantial interindividual variability. This toxicity is dose-dependent and more frequent in weekly paclitaxel regimens, 8,9 in patients with diabetes, previous neurotoxic chemotherapy treatments and in patients with pre-existing neuropathies. 10,11 Age and gender might also be risk factors [11][12][13] and decreased levels of plasma nerve factors might have a role in the neurotoxicity.…”

A randomized phase III study comparing three anthracycline-free taxane-based regimens, as first line chemotherapy, in metastatic breast cancer

“…Its superiority over the standard 3-weekly administration (175 mg/m 2 over 3-h infusion) was demonstrated in a randomized study [23], conducted by the Cancer and Leukemia Group B (CALGB). In that study, weekly paclitaxel was found to be superior to the 3-weekly regimen in terms of ORR (42% vs 29%, P = 0.0004) and TTP (9 months vs 5 months, P = 0.0001).…”

Evaluation of Efficacy and Safety of Upfront Weekly Nanoparticle Albumin-bound Paclitaxel for HER2-negative Breast Cancer

“…Moreover, most studies of neoadjuvant Nab-PTX in breast cancer reported on the every-3-week (q3w) Nab-PTX administration regimen (16,17,(19)(20)(21) (22). Chemotherapy agents, including taxanes, which are recommended in the metastatic (23) and adjuvant settings (24), are also considered in the neoadjuvant setting.…”