Clin Cancer Res
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The humanized monoclonal antibody, trastuzumab (Herceptin), directed against HER2/neu, has been effective in the treatment of breast cancer malignancies. However, clinical activity has depended on HER2/neu expression. Radiolabeled trastuzumab has been considered previously as a potential agent for radioimmunotherapy. The objective of this study was to investigate the efficacy of trastuzumab labeled with the alpha-particle emitting atomic generator, actinium-225 ((225)Ac), against breast cancer spheroids with different HER2/neu expression levels. (225)Ac has a 10-day half-life and a decay scheme yielding four alpha-particles. ⋯ These studies suggest that (225)Ac-labeled trastuzumab may be a potent therapeutic agent against metastatic breast cancer cells exhibiting intermediate to high HER2/neu expression.
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This is a dose-finding Phase I study of oral Ro 31-7453, a new class of antimitotic drug with promising preclinical activity in several chemoresistant models. ⋯ Both Ro 31-7453 regimens were feasible, but the 14-day schedule at the recommended dose of 125 mg/m(2) bid was selected for further monotherapy Phase II evaluation because of its higher preclinical activity. This regimen is convenient, well tolerated, and has a favorable pharmacokinetic profile.
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There is an urgent need for new therapies to treat non-small cell lung cancer (NSCLC) because current chemotherapy regimens are of limited effectiveness. The role of vascular endothelial growth factor in promoting tumor angiogenesis, in maintaining existing vasculature, and in resistance to traditional therapies, together with its negative prognostic significance in NSCLC, make it an appropriate target for therapy. Bevacizumab (Avastin), a monoclonal antibody directed against vascular endothelial growth factor, has shown promise in treating a number of different cancers. ⋯ Serious tumor-related bleeding episodes (hemoptysis/hematemesis) seem to be the main safety concern in patients with NSCLC, with squamous cell histology as a possible risk factor. Present ongoing studies are under way in NSCLC including (a) a Phase II neo-adjuvant study in combination with paclitaxel and carboplatin in patients with stage IB-IIA NSCLC; (b) a Phase I/II study of bevacizumab in combination with the epidermal growth factor receptor tyrosine kinase inhibitor agent, Tarceva, in patients with previously treated NSCLC; and (c) an Eastern Cooperative Group randomized Phase III study of paclitaxel and carboplatin with/without bevacizumab in patients with previously untreated IIIB (malignant pleural effusion) or metastatic NSCLC. These studies will help to establish the role of bevacizumab in NSCLC.
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Oxaliplatin is active in colorectal cancer. Sensory neurotoxicity is its dose-limiting toxicity. It may come from an effect on neuronal voltage-gated Na channels, via the liberation one its metabolite, oxalate. We decided to use Ca and Mg as oxalate chelators. ⋯ Ca/Mg infusions seem to reduce incidence and intensity of acute oxaliplatin-induced symptoms and might delay cumulative neuropathy, especially in 85 mg/m(2) oxaliplatin dosage.
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Large, randomized trials have been conducted in the primary prevention of lung cancer using micronutrients or derivative agents for which epidemiological data suggested a potential role in lung cancer prevention. The disappointing primary prevention trials of beta-carotene, alpha-tocopherol, and retinyl palmitate have led to the development of a more compact, biomarker-driven series of translational trials of lung cancer prevention that target reversal of premalignancy as the primary end point. ⋯ Other planned or ongoing trials currently target important molecular markers of lung carcinogenesis and progression including cyclooxygenase-2, the ras-signaling pathway through farnesyl transferase inhibitors, and the tyrosine kinase/epidermal growth factor receptor pathway (gefitinib, erlotinib). Early results of bioadjuvant trials in head and neck cancer suggest that combination chemoprevention will ultimately be an important option.