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Introduction: Single agent chemotherapy is standard for second and third line treatment of non-small cell lung cancer (NSCLC). Combination therapy to date has not proven to be superior to single agents in this setting, often adding toxicity without any additional efficacy. We investigated the activity and tolerability of the combination of oxaliplatin, pemetrexed, and bevacizumab in patients with previously treated advanced NSCLC., Methods: This multicenter phase II trial evaluated the safety and efficacy of the combination of pemetrexed (500 mg/m), oxaliplatin (120 mg/m), and bevacizumab (15 mg/kg), given every 21 days, in patients with previously treated advanced NSCLC. Eligibility criteria included performance status 0 to 1, nonsquamous histology, and at least one prior chemotherapy regimen. Patients with treated brain metastases were allowed. The primary end point was response rate, with secondary endpoints of progression-free survival and overall survival., Results: Thirty-six patients were enrolled on this study. Treatment was well tolerated; the most common grade 3 toxicity was hypertension, which was easily managed with oral medications. The nine (25%) patients with treated brain metastases had no episodes of cerebral hemorrhage. Of the 34 patients evaluable for tumor response, none had complete response, nine (27%) had partial response, 15 (44%) had stable disease, and 10 (29%) had progressive disease. Median progression-free survival was 5.8 months (95% confidence interval 4.1-7.8 months) and median overall survival was 12.5 months (95% confidence interval 7.3-17 months)., Conclusions: Treatment with oxaliplatin and pemetrexed in combination with the targeted antiangiogenic agent bevacizumab yielded promising efficacy with manageable toxicity in the previously treated advanced NSCLC population.

The leukocyte sialyloglycoprotein CD43 exhibits features of a signal transducing molecule and is thought to be important for T-cell activation and adhesion. However, cellular biochemical events in which CD43 participates remain poorly understood. Here we provide evidence that CD43 regulates tyrosine phosphorylation of a specific substrate in T cells. A 93-kD tyrosine phosphoprotein was identified specifically in the CD43+ T-cell line CEM, but not in their CD43-deficient counterparts derived by gene targeting. The 93-kD phosphoprotein was detected in the CD43-deficient CEM cells after transfection with CD43 cDNA, and it could be specifically phosphorylated in lysates from the CD43-deficient cells by incubation with a CD43 immunoprecipitate obtained from the CD43+ cells. Expression of CD43 in HeLa cell transfectants was associated with the appearance of novel phosphoproteins including one with a molecular weight of approximately 93 kD, confirming that tyrosine phosphorylation of cellular substrates results specifically from CD43 expression. We conclude that CD43 regulates tyrosine phosphorylation of a 93-kD T-cell substrate.