A Multi-institutional Phase 2 Study of Imatinib Mesylate and Gemcitabine for First-Line Treatment of Advanced Pancreatic Cancer.

Abstract

BACKGROUND: The pancreatic tumor microenvironment is rich in receptors for platelet-derived growth factor (PDGFRs). Imatinib mesylate (IM) inhibits PDGFRs and decreases tumor interstitial fluid pressure, potentially improving drug access. These data and promising results in a phase 1 trial formed the rationale for a phase 2 trial combining IM and gemcitabine (GEM) in pancreatic cancer. METHODS: Eligibility criteria included chemotherapy-naïve, locally advanced or metastatic pancreatic cancer; ECOG (Eastern Cooperative Oncology Group) performance status ≤2; and adequate end-organ function. The primary end point was progression-free survival (PFS). Secondary end points included response rate, toxicity, and overall survival (OS). GEM was given at 1200 mg/m(2)/120 min on days 3 and 10. IM (400 mg) was taken orally on days 1 to 5 and 8 to 12 of a 21-day cycle. Response was assessed every 3 cycles. RESULTS: Forty-four patients from 7 centers were enrolled from October 2005 through July 2009. Median age was 62 years. The median number of cycles completed was 3 (range, 0-17). Common adverse effects included neutropenia, nausea, anemia, and fatigue. Half the patients required dose reductions. There were no complete responses to therapy. During treatment, 1 patient showed a partial response, 16 had stable disease, and 18 had progressive disease. The median PFS was 3.9 months (95% confidence interval, 2.1-5.1), the median OS was 6.3 months (95% confidence interval, 5.2-8.5), and the 1-year survival rate was 25.6% (95% confidence interval, 13.8-39.1). CONCLUSION: IM in combination with GEM is tolerated in locally advanced, metastatic, or recurrent pancreatic cancer, but does not show a statistically significant PFS or OS benefit over chemotherapy with GEM alone.