P5-19-05: Age-Related Changes in the Pharmacokinetics (pK), Response, and Toxicity of Weekly nab-Paclitaxel in Patients with Metastatic Breast Cancer (MBC).

Background: Although cancer is a disease of aging, few studies have evaluated the association between patient age and the pK or pharmacodynamics (pD) of cancer therapeutics. The goals of this study were 1) to evaluate the age-related changes in the pK and pD of weekly nab -paclitaxel in patients with MBC; 2) to determine response rate; and 3) to explore the relationship of age with pK and pD parameters (i.e., dose reductions, dose delays and grade ≥ 3 toxicities). Patients and Methods: Forty patients with MBC, receiving 1 st or 2 nd line chemotherapy, entered an IRB approved protocol to evaluate the age-related changes in the pK of weekly nab -paclitaxel administered at 100 mg/m 2 IV for 3 weeks followed by a 1-week break. Patients were accrued from 4 age strata 70 years of age. Blood samples were collected for pK analysis with the first dose of nab -paclitaxel. Response was assessed every 2 cycles. Toxicity was graded using the NCI Common Toxicity Criteria for Adverse Events (v 3.0) and was adjudicated as attributable to nab -paclitaxel if it was possibly, probably, or definitely related. Linear regression analysis was used to examine the strength of the relationship between patient age and natural logarithm of 24 hour area under the curve (AUC). Two-sided two-sample t-tests were used to assess if there was a difference in mean age based on the presence of pD variables (i.e., dose reductions, dose delays and grade ≥ 3 toxicities). The significance level was set to 0.05. Results: Of the 40 patients who entered the study, 39 (98%) were evaluable with a mean age of 60 (SD=13.4; min=30; max=81). Patients were accrued in the following age cohorts: 70 (n= 9; 23%) years of age. The median number of courses completed was 4 (min=1, max=21). The response rate was: 0% (n=0) CR, 31% (n=12) PR, 38% (n=15) SD. Grade 3 toxicity was experienced by 26% (n=10). We observed 8% (n=3) grade 3 hematological toxicities [neutrophils (n=1; 3%), leukocytes (n=2; 5%)] and 18% (n=7) grade 3 non-hematological toxicities [nausea and hypophosphatemia (n=1; 3%), diarrhea and infection without neutropenia (n=1; 3%), fatigue (n=2; 5%), hyponatremia (n=1; 3%), and infections without neutropenia (n=2; 5%)]. There were no cases of grade 4 or 5 toxicity. Grade 2 sensory neuropathy was experienced by 8% (n=3; no cases in the 70+ age cohort). Dose reductions or course delays were experienced by 62% (n=24) and 21% (n=8), respectively. There was a borderline significant positive association between age and natural logarithm of total nab -paclitaxel 24 hour AUC (coef=.01; se=.006; p=0.055; n=36). There were no differences in the mean ages based on the presence of grade 3 or higher toxicity (p =0.75), need for dose reductions (p=0.48), or need for dose delays (p=0.61). Discussion: There is a borderline statistically significant relationship between age and 24 hour AUC but no differences in mean age based on pD variables (i.e., dose reductions, dose delays and grade ≥ 3 toxicities) were identified. The treatment is well-tolerated across all age groups. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-19-05.