Background This study aimed to characterize the neurotoxicity of three different regimens of nab‐paclitaxel compared with a standard regimen of solvent‐based (sb) paclitaxel for the first‐line treatment of HER2‐negative metastatic breast cancer based on the Total Neurotoxicity Score (TNS), a tool specifically developed to assess chemotherapy‐induced neurotoxicity. Materials and Methods This was a randomized, open‐label study testing 4‐week cycles of 80 mg/m2 sb‐paclitaxel (PACL80/w) on days 1, 8, and 15; 100 mg/m2 nab‐paclitaxel on days 1, 8, and 15 (NAB100/w); 150 mg/m2 nab‐paclitaxel on days 1, 8, and 15 (NAB150/w); and 150 mg/m2 nab‐paclitaxel on days 1 and 15 (NAB150/2w). In addition to the TNS, neuropathy was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI‐CTCAE). Tumor response and quality of life were also evaluated. Results Neurotoxicity, as evaluated by the TNS, did not significantly differ between the sb‐paclitaxel group and any of the nab‐paclitaxel groups. The frequency of (any grade) polyneuropathy, as measured by the NCI‐CTCAE, was lower in the PACL80/w (n = 7, 50%) and NAB150/2w (n = 10, 62.5%) groups than in the NAB100/w (n = 13, 81.3%) or NAB150/w (n = 11, 78.6%) group. Although the differences were not statistically significant, compared with the other groups, in the NAB150/w group, the time to occurrence of grade ≥2 polyneuropathy was shorter, and the median time to recovery from grade ≥2 polyneuropathy was longer. Dose delays and reductions due to neurotoxicity and impact of neurotoxicity on the patients’ experience of symptoms and functional limitations was greater with NAB150/w. Among the seven polymorphisms selected for genotyping, the variant alleles of EPHA5‐rs7349683, EPHA6‐rs301927, and EPHA8‐rs209709 were associated with an increased risk of paclitaxel‐induced neuropathy. Conclusion The results of this exploratory study showed that, regardless of the dose, nab‐paclitaxel did not differ from sb‐paclitaxel in terms of neurotoxicity as evaluated with the TNS. However, results from NCI‐CTCAE, dose delays and reductions, and functional tools consistently indicate that NAB150/w regimen is associated with a greater risk of chemotherapy‐induced neuropathy. Thus, our results question the superiority of the TNS over NCI‐CTCAE for evaluating chemotherapy‐induced neuropathy and guiding treatment decisions in this context. The selection of the nab‐paclitaxel regimen should be individualized based on the clinical context and potentially supported by pharmacogenetic analysis. Registry: EudraCT, 2012‐002361‐36; NCT01763710 Implications for Practice The results of this study call into question the superiority of the Total Neurotoxicity Score over the National Cancer Institute Common Terminology Criteria for Adverse Events for evaluating chemotherapy‐induced neuropathy and guiding treatment decisions in this context and suggest that a regimen of 150 mg/m2 nab‐paclitaxel administered on days 1, 8, and 15 is associated with a greater risk of chemot...

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e16084 Background: Vinorelbine (VRL) has been shown to be active in hormone-refractory prostate cancer (HRPC). Oral formulation of VRL represents a significant advance in the treatment of advanced cancer. The recommended doses are 60–80 mg/m2(d1–8 q3wks).We evaluated efficacy and toxicity of different VRL schedule administered as a fixed-weekly dose of 60 mg/m2. The purpose of this study was to evaluate the toxicity profile and efficacy of this schedule in terms of PSA response, objective response and clinical benefit (CB) response. Methods: Pts characteristics were: PS 0–2, adequate bone marrow, liver and renal functions. Oral VRL was adminestered at weekly dose of 60 mg/m2 until disease progression/intolerable toxicity. PSA response was defined as a >50% fall in PSA from baseline, confirmed by a second PSA value 4 or > weeks later. Pts with measurable soft tissue disease met traditional guidelines for tumour responses. Progression was defined by objective disease progression or PSA increase of >50% above nadir or >25% above baseline. Pts were monitored clinically and with serial PSA measurements every 1 week. Results: Thirty seven pts with progressive HR metastatic prostate cancer were evaluated. Mean (range) age was 67 years (50–88), median PSA level was 90 ng/ml (1- 4314), and median Gleason score was 7 (6–9). 23 (62%) pts had previous taxane chemotherapy and 14 pts (38%) were chemo-naive. Pts received a mean of 5.5 cycles (1cycle=3wks) (range:1–24). Median follow-up was 12 months. Thirty three of 37 Pts (97%) achieved a decline in serum PSA. CB response was achieved in 15 out of 37 pts(40%). The PSA response was observed in 13 pts (35%). Objective response was not observed and only 6 pts showed SD (16%). The relative dose-intensity was 94%. There were no reported grade 3–4 toxicities. Only 1 treatment discontinuation was observed (esopahgitis g2). Toxicities consisted primarily of g2 anemia (25%) and mild nausea (32%). Conclusions: Oral Vinorelbine administered as a fixed-weekly schedule of 60 mg/m2 is a safe regimen in pts with advanced HRPC. This regimen of oral vinorelbine is an effective and well-tolerated treatment in this setting, despite a major dose-intensity administered. Further studies will be evaluated in chemo-naive and/or elderly population. No significant financial relationships to disclose.