Phase II pharmacokinetic (PK) and pharmacodynamic (PD) study of OSI-7904L in previously untreated patients (pts) with advanced gastric or gastroesophageal junction cancer (G/GEJC)

4042 Background: OSI-7904L is a liposomal TS inhibitor with increased plasma residence and superior preclinical antitumor activity compared to parent drug or 5-FU. Methods: A 2-stage Simon design was used to evaluate the activity of OSI-7904L in G/GEJC, administered at 12 mg/m2 over 30 min every 21 days. Eligibility criteria included pathologically confirmed G/GEJC, ECOG PS 0–2, no prior chemo for advanced disease and ≥1 measurable lesion per RECIST. Secondary endpoints were safety, time to progression (TTP), survival and PK/ PD endpoints (TS genotype, 2’-dU and homocysteine). Results: Fifty of 53 enrolled pts were treated. Median age was 64 years (range 35–82), 62% were male and 90% had ECOG PS 0/1. Primary site was gastric in 80% of pts and GEJ in 20%. Two-thirds of pts had recurrent or metastatic disease; main sites of metastases were liver and lymph node. To date, 215 cycles have been given, median of 4/pt (range 1–12+). Eleven pts required dose reductions, mainly for skin toxicity (8 pts). Reductions...