Deep venous thrombosis caused by inferior vena cava atresia and hereditary thrombophilia.

Inferior vena cava (IVC) atresia is a risk factor for deep vein thrombosis (DVT) in young patients. Although Doppler ultrasound diagnoses DVT, a contrast-enhanced computerized tomography (CT) or magnetic resonance angiography (MRA) diagnoses IVC atresia, other congenital IVC anomalies and must be considered in young patients presenting with idiopathic DVT. Patients with IVC atresia associated with hereditary thrombophilia are at increased risk for recurrent DVT and may require long-term anticoagulation. We report 2 cases: the first one, a 33-year-old man with lower extremity DVT caused by IVC atresia in association with multiple thrombophilic risk factors; the second one, a 34-year-old woman with lower extremity DVT caused by IVC atresia in association with prothrombin gene mutation. To our knowledge, this association has not been reported. The clinical presentation, tools for diagnosis, and the need for long-term anticoagulation are discussed.

Phase I and pharmacokinetic study of imatinib mesylate (Gleevec) and gemcitabine in patients with refractory solid tumors.

PURPOSE: Preclinical data shows improvements in response for the combination of imatinib mesylate (IM, Gleevec) and gemcitabine (GEM) therapy compared with GEM alone. Our goals were to determine the maximum tolerated dose of GEM and IM in combination, the pharmacokinetics of GEM in the absence and in the presence of IM, and IM pharmacokinetics in this combination. PATIENTS AND METHODS: Patients with refractory malignancy, intact intestinal absorption, measurable/evaluable disease, adequate organ function, Eastern Cooperative Oncology Group PS 0-2, and signed informed consent were eligible. Initially, treatment consisted of 600 mg/m2 of GEM (10 mg/m2/min) on days 1, 8, and 15, and 300 mg of IM daily every 28 days. Due to excessive toxicity, the schedule was altered to IM on days 1 to 5 and 8 to 12, and GEM on days 3 and 10 every 21 days. Two final cohorts received IM on days 1 to 5, 8 to 12, and 15 to 19. RESULTS: Fifty-four patients were treated. IM and GEM given daily at 500 to 600 mg/m2 on days 1, 8, and 15 produced frequent dose-limiting toxicities. With the modified scheduling, GEM given at 1,500 mg/m2/150 min was deliverable, along with 400 mg of IM, without dose-limiting toxicities. Three partial (laryngeal, renal, and mesothelioma) and two minor (renal and pancreatic) responses were noted at GEM doses of 450 to 1,500 mg/m2. Stable disease >24 weeks was seen in 17 patients. CA19-9 in 7 of 10 patients with pancreatic cancer was reduced by approximately 90%. IM did not significantly alter GEM pharmacokinetics. CONCLUSION: The addition of intermittently dosed IM to GEM at low to full dose was associated with broad antitumor activity and little increase in toxicity.