Background: The use of single agent cytotoxic or targeted agent as maintenance following combination therapy represents a useful strategy to improve patient outcomes in advanced stage NSCLC. An earlier study with gemcitabine as maintenance therapy demonstrated improved time to progression (TTP) compared to BSC (6.6 mos. vs 5.0 mos., p < 0.001) (Brodowicz et al, Lung Cancer, 2006; 52:155-163). Based on this, we conducted a randomized phase III study to compare G + BSC versus BSC as maintenance therapy for patients with advanced NSCLC. Methods: Patients with stage IIIB (wet)/IV NSCLC were initially treated with gemcitabine (1,000 mg/m 2 on day 1 and 8) and carboplatin (AUC = 5 mg/mL.min on d 1) every 3 weeks for 4 cycles. Subsequently, patients with CR/PR or SD were randomized 1:1 to receive maintenance G (1,000 mg/m 2 on d 1 and 8), every 3 weeks with BSC or BSC alone until disease progression. The primary endpoint was the comparison of overall survival between the two arms and the secondary endpoint was progression free survival (PFS). Results: 519 patients were enrolled (median age-67 years, stage IV disease-86%, ECOG performance status 0/1-75%). With G-Cb, the RR was 28% (CR-1.2%, PR-26.8%), and 37% had SD. Following 4 cycles of G-Cb, 255 non-progressors were randomized to receive G + BSC (n = 128) or BSC (n = 127). The median PFS was 3.9 m (95% CI:3.3, 5.6) for G + BSC and 3.8 m (95% CI: 2.6, 5.5) for BSC. Median survival was 8.0 m (95% CI: 6.0, 10.2) for G+ BSC and 9.3 m (95% CI: 7.7, 12.7) for BSC. The differences in survival between the two arms were not statistically significant (HR = 0.97 [95% CI: 0.72, 1.30], p = 0.84). Maintenance therapy was tolerated well despite a higher incidence of grade 3/4 toxicity (anemia 9.4% vs. 2.4%; neutropenia 13.3% vs. 1.6%; thrombocytopenia 9.4% vs. 1.4%; and fatigue 3.9% vs. 1.6%). Conclusions: The use of gemcitabine as maintenance therapy failed to improve survival following G-Cb in patients with advanced NSCLC.

We describe a patient who developed a markedly prolonged PT, PTT, and thrombin time 13 days after repeat exposure to fibrin sealant during coronary artery bypass grafting and aortic valve replacement. Evaluation revealed an inhibitor to bovine thrombin that cross-reacted with human thrombin. In addition an inhibitor to human coagulation factor V was identified. Despite coagulation abnormalities there was no evidence of bleeding. Nevertheless, effective anticoagulation was required to minimize the thrombotic complications associated with the patient's prosthetic valve. We elected to take a conservative approach and not utilize pharmacologic anticoagulation until there was diminution in the effect of the acquired inhibitors. We report on our patient's course and review the available literature addressing the management of patients demonstrating inhibitors to blood coagulation factors after repeat exposure to fibrin sealants.

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Gemcitabine as a single agent, in this dosage and schedule, has minimal clinical activity in relapsed or refractory low-grade lymphomas and was associated with considerable toxicity. Therefore, further study of gemcitabine in this setting is not justified.

18025 Background: As single agents, oxaliplatin and pemetrexed have shown activity in patients with non-small cell lung cancer (NSCLC) and pemetrexed has demonstrated synergistic effectiveness when combined with platinum-based drugs. Moreover, bevacizumab has an additive effect on many chemotherapy agents in several tumor types, including NSCLC. The purpose of this phase II, open-label, non- randomized study is to evaluate the efficacy and safety of the combination of bevacizumab, oxaliplatin, and pemetrexed as first-line treatment for NSCLC. This report presents preliminary safety information demonstrating the safety and tolerability of this combination. Methods: Patients = 18 years with histologically/pathologically confirmed Stage IIIB/IV non-squamous NSCLC received 6 cycles of oxaliplatin (120 mg/m2), pemetrexed (500 mg/m2), and bevacizumab (15 mg/kg) on Day 1 of each 21-day cycle. Following 6 cycles, patients received bevacizumab alone every 21 days until disease progression or unacceptable toxicity. Results: At the time of analysis, 53 subjects received study medication and are evaluable for safety. Patient characteristics include: gender male/female/unknown, 16/34/3; median age 62.0 years (range 43–86); and ECOG performance status 0/1/unknown, 24/25/4. The median number of cycles administered is 4 (range 1–11). Fifty patients are still on study. The most common Grade 3 toxicities were neutropenia (10.4%), dyspnea (6.0%), fatigue (4.5%), thrombocytopenia (4.5%), hyperglycemia (4.5%), nausea (3.0%), and vomiting (3.0%). Grade 4 toxicities were dyspnea (1.5%), hyperglycemia (1.5%), asthenia (1.5%), thrombocytopenia (3.0%), neutropenia (3.0%), and pulmonary embolism (1.5%). Three patients died; 2 of progressive disease and 1 of hypoxia (not likely related to study drugs). Conclusions: These preliminary results suggest that the combination of oxaliplatin, pemetrexed, and bevacizumab demonstrates an acceptable safety profile for first-line treatment of stage IIIB/IV NSCLC. Conclusions concerning the efficacy of this combination await further treatment information. Supported by Genentech, Inc., Sanofi-Aventis, and Eli Lilly and Company. [Table: see text]