15130 Background: PPX is a conjugate of paclitaxel to a polyglutamate polymer. Preclinically, PPX demonstrated a radiation enhancement factor (REF) >7.0, versus 1.5–2.0 for paclitaxel. (Milas et al Int J Rad Onc 55:2003, Li et al. Clin Cancer Res 6:2000). The maximally tolerated dose (MTD) of PPX was determined previously to be 70 mg/m2 /week with concurrent radiation. We initiated a phase I study of PPX, cisplatin, and concurrent radiation with patients with esophageal and gastric cancer. Methods: Patients with esophageal or gastric cancer receiving chemoradiation for locoregional control, adjuvant, or neoadjuvant treatment were eligible. All patients received radiation at a dose of 50.4 Gy delivered in 28 fractions (5 fractions per week for 5 1/2 weeks), and cisplatin (25 mg/m2) on days 1, 8, 15, 22, 29, and 36. PPX was given as a 10 minute infusion in escalating dosages prior to each cisplatin dose. Dose limiting toxicities (DLTs) were defined as grade 4 hematologic toxicity, esophagitis, nausea/vomiting, or dehydration, or any other grade 3/4 non-hematologic toxicity. Patients were enrolled in successive cohorts of three. The MTD was defined as the dose level at which no more than 2 of 6 patients have DLTs. Results: Eleven patients have been entered over 2 dose levels of PPX: 50 mg/m2 (six patients, dose level 1), and 60mg/m2 (5 patients, dose level 2). Five patients had esophageal cancer and six had gastric cancer. All histologies were adenocarcinomas. One of six patients treated at dose level had a DLT (esophagitis). Three of five patients had DLTs at dose level 2, including esophagitis, nausea, vomiting, and dehydration. Conclusions: PPX is a novel radiation sensitizer for patients with esophageal and gastric cancer. The MTD for PPX is 50 mg/m2 /week in combination with cisplatin 25mg/ m2 /week for 6 weeks, and 50.4 Gy concurrent radiation for patients with esophagogastric cancer. A phase II study of PPX/cisplatin and radiation will be initiated. No significant financial relationships to disclose.
Safety and immunogenicity of neoadjuvant treatment using WT1-immunotherapeutic in combination with standard therapy in patients with WT1-positive Stage II/III breast cancer: a randomized Phase I study
