GW572016治疗晚期胰腺胆道肿瘤的I期临床研究

        GW572016, gemcitabine and GW572016, gemcitabine, oxaliplatin, a two-stage, phase I study for advanced pancreaticobiliary cancer.

Meeting:　2006 ASCO Annual Meeting　
　

Abstract No: 4002
Citation: Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 4002
Author(s): H. Safran, D. Iannitti, T. Miner, K. Demel, D. Yoo, P. Joseph, C. Maia-Acuna, L. Lockridge, D. Evans, K. Teresa
Abstract: Background: GW572016 is an orally active small molecule that reversibly inhibits ErbB1 and ErbB2 tyrosine kinases. ErbB1 is commonly expressed in pancreaticobiliary cancers. ErbB2 is the preferred heterodimer partner for other ErbB receptors. Baerman et al demonstrated that GW572016 was active against pancreatic cancer cell lines (ASCO GI 2005). We have completed a two-stage, phase I evaluation of GW572016 and gemcitabine (gem), and GW572016 with the combination of gemcitabine and oxaliplatin (GEMOX). Methods: Patients with advanced adenocarcinoma of the pancreas or bile ducts were treated with GW572016 and either weekly gemcitabine (1gm/m2/week, 3 weeks on, 1 week off) or GEMOX (gemcitabine 1g/m2 over 100 minutes and oxaliplatin 100 mg/m2, every 14 days). Cohort 1: Weekly gem + GW572016, 1000mg/day. Cohort 2: Weekly gem + GW572016, 1500 mg/day. Cohort 3: GEMOX + GW572016 1000 mg/day. Cohort 4: GEMOX + GW572016 1500 mg/day. Results: Twenty-one patients have been treated; pancreatic cancer (n=15), biliary cancer (n=6). The median age was 64 (41-78). One of six patients in cohort 2 had grade 3 diarrhea. Dose limiting grade 3 nausea occurred in 2 of 5 patients in cohort 4. Two patients had a temporary decrease in cardiac ejection fraction. Five of 20 evaluable patients (25%) responded. Conclusions: GW572016 1500 mg/day can be administered will full dosage gem. The MTD of GW572016 is 1000mg/day with GEMOX. Dramatic responses have been demonstrated in patients with diffuse liver and peritoneal metastases suggesting that erbB1/erbB2 signaling is important in pancreaticobiliary cancers. Further evaluation of GW572016 in pancreaticobiliary cancer is indicated.