Purpose Gemcitabine plus nanoparticle albumin-bound (NAB) paclitaxel (GA) significantly improved survival compared with gemcitabine alone in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) and a Karnofsky performance status (PS) of 70% or greater. Because of the low number of patients with reduced PS, the efficacy of this regimen in fragile patients remains unclear. This study aimed to evaluate the efficacy and tolerability of different GA dosing regimens in patients with a poor PS. Patients and Methods In the phase I part of this study, patients were randomly assigned to one of the following four parallel GA treatment arms (six patients per arm): a biweekly schedule of NAB-paclitaxel (150 mg/m2 [arm A] or 125 mg/m2 [arm C]) plus gemcitabine 1,000 mg/m2 or a standard schedule of 3 weeks on and 1 week off of NAB-paclitaxel (100 mg/m2 [arm B] or 125 mg/m2 [arm D]) plus gemcitabine 1,000 mg/m2. The two regimens with the better tolerability profile on the basis of predefined criteria were evaluated in the phase II part of the study, the primary end point of which was 6-month actuarial survival. Results Arms B and D were selected for the phase II part of the study. A total of 221 patients (111 patients in arm B and 110 patients in arm D) were enrolled. Baseline characteristics including median age (71 and 68 years in arms B and D, respectively), sex (51% and 55% men in arms B and D, respectively), and metastatic disease (88% and 84% in arms B and D, respectively) were comparable between arms. The most frequent grade 3 or 4 toxicities in arms B and D were anemia (12% and 7%, respectively), neutropenia (32% and 30%, respectively), thrombocytopenia (7% and 11%, respectively), asthenia (14% and 16%, respectively), and neurotoxicity (11% and 16%, respectively). In arms B and D, there were no significant differences in response rate (24% and 28%, respectively), median progression-free survival (5.7 and 6.7 months, respectively), and 6-month overall survival (63% and 69%, respectively). Conclusion NAB-paclitaxel administered at either 100 and 125 mg/m2 in combination with gemcitabine on days 1, 8, and 15 every 28 days is well tolerated and results in acceptable safety and efficacy in patients with metastatic pancreatic ductal adenocarcinoma and a poor PS.

4613 Background: Trastuzumab(T) exhibits activity in human gastric cancer cells that overexpress HER2/neu. We previously reported a 13.5% HER2/neu overexpression/amplification in AGC or gastroesofageal junction (GEJ) cancers (Grávalos C, et al. J Clin Oncol 24, 18S, 200s, abstr # 4089). We designed a phase II trial to determine the efficacy and tolerability of T and cisplatin(C) in pts with ACG with HER2/neu overexpression/amplification. Exploratory objectives include analysis of c-erbB-2 extracellular domain and correlation of the results with histological erB-2/neu overexpression and with clinical response Methods: Chemo-naïve pts with adenocarcinoma histopatologically confirmed, HER2/neu overexpression/amplification, measurable, no operable, locally advanced or metastatic AGC, age ≥ 18, ECOG ≤ 2, FEVI ≥ 50% and adequate organ function were eligible. Prior adjuvant radiotherapy or/and chemotherapy were allowed. Immunohistochemistry (IHC) was performed using herceptest. A fluorescence in situ hybridization (FISH) assay was done when IHQ was = 2. HER2/neu expression was considered negative if IHC= 0, 1 or IHC=2 and FISH -; and positive if IHC=2 and FISH + or IHC=3. T 8 mg/kg d1 (loading dose in first cycle) and 6 mg/kg (maintenance doses) and C 75 mg/m2 d1 were administered every 21 days until progression, unacceptable toxicity or withdrawal inform consent Results: 21 pts has been included. 17 are evaluable. 16 were men. Median age 66 (50–78). ECOG 0/1: 5/12. Histological subtypes were: 50% intestinal, 25% diffuse and 25% unknown. 56% had gastric localization and 44% GEJ. 16 pts had metastases (59% liver, 47% lymph nodes, 23% peritoneum, 17% lung, and 24% others). Prior treatment: 5 pts underwent surgery and 2 had adjuvant chemotherapy. Median cycles 2 (1–14). Efficacy: 6 (35%) pts achieved response (1/5 CR/PR), 3 (17%) stabilization (52% control disease = RC + PR+SD), 4 pts with progression disease, 4 pts too early Tolerance: There was no grade 4 toxicity. Main grade 3 adverse events included: asthenia (3 pts), nauseas/vomiting (3), diarrhea (2), hiporexia (2) and neutropenia (1) Conclusions: Trastuzumab and cisplatin is a well tolerated regimen with a promising activity. The study is ongoing and an update will be presented at the meeting. No significant financial relationships to disclose.