Gloria Chia

PURPOSE: Nanoparticle albumin-bound paclitaxel (NAB-paclitaxel) is an albumin-bound formulation of paclitaxel that has demonstrated improved efficacy compared with paclitaxel in the treatment of metastatic breast cancer. We undertook this trial to determine the maximum-tolerated dose (MTD) and single-agent activity of NAB-paclitaxel administered on a weekly basis to patients with stage IV non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: This was an open-label, single-arm, phase I/II study. Patients were treated with NAB-paclitaxel intravenously during 30 minutes without corticosteroid or antihistamine premedications on days 1, 8, and 15 of a 28-day cycle. Radiologic tumor assessment was performed every 8 weeks. RESULTS: Dose levels of 100 and 125 mg/m(2) were tolerated without dose-limiting toxicities (DLTs). At 150 mg/m(2) the MTD was exceeded; two of three patients experienced a DLT (grade 3 sensory neuropathy and febrile neutropenia). The 125 mg/m(2) dose level was expanded and determined to be the MTD. A total of 40 patients were treated at 125 mg/m(2). The objective response rate was 30% (12 of 40 patients; 95% CI, 16% to 44%), median time to progression was 5 months (95% CI, 3 to 8 months), and median overall survival was 11 months (95% CI, 7 months to not reached). The 1-year survival was 41%. CONCLUSION: NAB-paclitaxel 125 mg/m(2) administered on days 1, 8, and 15 of a 28-day cycle was well tolerated and demonstrated encouraging single-agent activity. No corticosteroid premedication was administered and no hypersensitivity reactions were seen. Additional studies of single-agent NAB-paclitaxel as well as platinum-based combinations are warranted.

Tunicamycin, an antibiotic that inhibits protein glycosylation, elicited a rapid depletion of insulin binding activity at the surface of 3T3-L1 adipocytes. Disappearance of insulin receptors occurred more rapidly in the presence of tunicamycin than when protein synthesis was inhibited by cycloheximide and was accompanied by a diminution in sensitivity of the adipocytes to the acute effects of insulin and anti-insulin receptor antibody on hexose uptake and metabolism.

7105 Background: ABI-007 is a 130-nm albumin-bound form of paclitaxel. This study was designed to determine (1) the MTD and DLTs of ABI-007 in patients with stage IV chemotherapy-naive NSCLC and (2) the efficacy and safety of ABI-007 at the MTD. Methods: Eligibility requirement included ECOG PS 0–1, adequate organ function and sensory neuropathy ≤ grade 1. No prior chemotherapy for metastatic disease was allowed. Prior EGFR TKI therapy was allowed. ABI-007 was administered on days 1, 8, and 15 every 28 days (IV over 30 min. without premedication). In the phase I portion, 3 dose levels were studied (100, 125 and 150 mg/m 2 ) and in the phase 2 portion, 40 patients were treated at the MTD. Results: 50 patients received ABI-007; the median age was 70 yo and 76% of patients were ≥ 65 yo. No DLTs were observed at the 100 and 125 mg/m 2 dose level. However at the 150 mg/m 2 dose level 2/6 patients had a DLT (febrile neutropenia and sensory neuropathy, respectively) during cycle 1 such that the MTD was exceeded. The 125 mg/m 2 dose level was identified as the MTD and expanded to 40 patients in the phase 2 portion of this study. Toxicity and efficacy data is presented for the phase 2 portion. Ten patients (25%) had received prior neoadjuvant or adjuvant chemotherapy and 5 (13%) had received prior gefitinib or erlotinib. Sensory neuropathy was the most frequent toxicity with grade 2 and 3 toxicity occurring in 8% and 15% of patients. Grade 2 and 3 fatigue was observed in 8% and 13% of patients. Grade 3 and 4 neutropenia occurred in 10% and 3% of patients with no febrile neutropenia observed. Response was assessed by RECIST. One CR and 14 PRs were observed for an overall response rate of 15/40 (38%). The median survival was 10.3 months. Conclusions: The MTD for ABI-007 administered over 30 min. on days 1, 8, and 15 every 28 days was 125 mg/m 2 . No hypersensitivity reactions were observed and no premedication was given. In the phase 2 portion, a 38% response rate and 10.3 month survival was observed. Non-hematologic toxicities were primarily sensory neuropathy and fatigue. Myelosuppression was minimal and no febrile neutropenia was observed. Further development of ABI-007 in NSCLC is warranted based on the encouraging single agent activity observed in this study. [Table: see text]

18087 Background: We have previously reported that nab-paclitaxel (ABI-007; Abraxane) administered at 125 mg/m 2 over 30 minutes on days 1, 8, and 15 every 28 days has a response rate (RR) of 30% and median survival of 11 months [Rizvi, Proc. ASCO 2006]. We also observed 15/40 (38%) patients developed grade 2/3 sensory neuropathy with a 30 minute infusion. We hypothesize that a longer infusion with nab-paclitaxel may reduce peak plasma levels and accordingly reduce sensory neuropathy. Methods: After enrollment of 40 patients at 125 mg/m 2 over 30 minutes on days 1, 8, and 15 every 28 days, we amended the protocol to study an additional 25 patients with chemotherapy naïve stage IV NSCLC with a 2 hour infusion. The enrollment criteria and treatment schedule otherwise remained the same. Our goal was to detect 1 to 2 grade improvement of peripheral neuropathy with 80% power at the two sided p=0.10 significance level compared to the 40 patients treated with this dose given over 30 minutes. Results: To date, 22 of 25 planned patients have been treated with a 2 hour infusion. The mean number of doses administered was 11 for the initial 40 patients treated with a 30 minute infusion and 10 for the 22 patients treated with the 2 hour infusion. We observed 9/40 grade 2 and 6/40 grade 3 sensory neuropathy with the 30 minute infusion and 2/22 grade 2 and 1/22 grade 3 sensory neuropathy with the 2 hour infusion. The combined grade 2 and 3 toxicities were less with the 2 hour infusion (3/22, 14%) compared with the 30 minute infusion (15/40, 38%; p=0.078, Fisher’s exact test). Conclusions: Prolonging the infusion rate of nab-paclitaxel from 30 minutes to 2 hours is associated with a significant decrease in grade 2 and 3 sensory neuropathy. Efficacy data is presently being evaluated. [Table: see text]