Summary In this prospective study of patients with relapsed and/or refractory multiple myeloma (MM) treated with lenalidomide and dexamethasone, relationships between markers of endothelial stress and drug administration and incidence of venous thromboembolism (VTE) were assessed. Of 33 enrolled patients, laboratory and treatment data were available for 32 patients. Of these, 23 received pulsed dexamethasone (40 mg/day on days 1–4, 9–12, and 17–21 of each 28-day cycle) and 9 received weekly dexamethasone (40 mg/day on days 1, 8, 15, and 21 of each cycle). The overall incidence of VTE was 9%. A decreasing trend in markers values was observed with intercellular adhesion molecule (P = 0·05), fibrinogen (P = 0·008), plasminogen activator inhibitor-1 (P < 0·001), homocysteine (P = 0·002), and P-selectin (P < 0·001) during therapy. Compared with weekly dexamethasone, pulsed dexamethasone was associated with significantly greater variation in mean adjusted relative values of fibrinogen, P-selectin, and vascular endothelial growth factor (P < 0·001 for all comparisons), although there was no apparent association with VTE incidence. Lenalidomide plus dexamethasone affects endothelial stress marker levels in patients with advanced MM. The higher variation seen with pulsed dexamethasone suggests greater endothelial stress with this approach.

Aortic thrombus formation is rare in the patients with essential thrombocytosis (ET); therefore, no guidelines for its management have been established. Embolism from ET-associated large vessel thrombi is potentially lethal and has been managed surgically in a few reported cases. We describe herein a 45-year-old black woman with ET found to have a 3.5-cm, pedunculated intra-aortic thrombus at the thoracoabdominal junction. How to treat this potentially devastating aortic thrombus was a management dilemma. We believed, based on the patient's diagnosis of ET and the histology of similar thrombi in 1 reported series, that the aortic thrombus was a "white thrombus" consisting primarily of aggregated platelets with a minimal fibrin network and almost no entrapped erythrocytes. The patient was treated with aspirin, 325 mg daily, as a platelet antiaggregating agent and hydroxyurea, 1,500 mg daily, to reduce the platelet count to less than 450 x 10(9)/L. The thrombus resolved without severe thromboembolic events. To our knowledge, this is the first reported case of a large intra-aortic thrombosis associated with ET that has been successfully managed with medical therapy alone.

Aortic thrombus formation is rare in the patients with essential thrombocytosis (ET); therefore, no guidelines for its management have been established. Embolism from ET-associated large vessel thrombi is potentially lethal and has been managed surgically in a few reported cases. We describe herein a 45-year-old black woman with ET found to have a 3.5-cm, pedunculated intra-aortic thrombus at the thoracoabdominal junction. How to treat this potentially devastating aortic thrombus was a management dilemma. We believed, based on the patient's diagnosis of ET and the histology of similar thrombi in 1 reported series, that the aortic thrombus was a "white thrombus" consisting primarily of aggregated platelets with a mini-

4002 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. [Table: see text]