Seminars in oncology
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Seminars in oncology · Dec 2005
ReviewThe emerging role of vascular endothelial growth factor receptor tyrosine kinase inhibitors.
In the United States, non-small cell lung cancer (NSCLC) constitutes 85% of all newly diagnosed lung cancers. Over the past 40 years, the 5-year survival rates in NSCLC have improved from 6% to 15%, with surgery remaining the most curative approach. However, resection is feasible in less than 35% of patients at diagnosis, and 40% to 50% of newly diagnosed patients present with metastatic disease. ⋯ Based on toxicity observations from a phase II study, this trial excluded patients with squamous histology, brain metastases, or an ongoing need for therapeutic anti-coagulation or non-steroidal anti-inflammatory agents. Preliminary data confirmed a survival advantage of 12.5 months for patients in the bevacizumab arm compared with 10.2 months in the control arm (P = .0075), which showed that antiangiogenic therapies can be effective in NSCLC. Antiangiogenic therapies, including antibodies against VEGF, and, in particular, new small-molecule inhibitors of the VEGF receptor, are reviewed and discussed in detail.
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Despite slow clinical progress, efforts to develop specific nontoxic cancer gene therapies are increasing exponentially. Adenoviral vectors are one of the most popular vehicles for gene transfer currently being used in worldwide clinical trials for cancer. ⋯ In addition, novel approaches to tumor killing have also been explored, which will have greater potency and selectivity than currently available treatments such as chemotherapy or radiation. This review discusses the basic concepts behind the use of adenoviral vectors for cancer gene therapy and their potential for clinical application, as well as ongoing and completed clinical trials.
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The prognosis for the majority of patients with lung cancer remains poor, and treatment strategies including newer generation chemotherapeutics have not improved survival. New approaches are required to further improve patient outcome and survival. ⋯ The results of recent studies validate the use of this class of targeted therapeutics as an important new treatment modality in cancer therapy. This review will focus on a discussion of antiangiogenic therapeutic monoclonal antibodies in development for the treatment of non-small cell lung cancer.
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Gastric resection of all gross and microscopic disease is the only proven, potentially curative treatment of gastric cancer; however, because lymph node metastasis frequently occurs early in the disease, a regional lymphadenectomy is also recommended as part of a radical gastrectomy. Controversy exists regarding whether the extent of lymph node dissection should be limited to the perigastric lymph nodes (D1), or include the regional lymph nodes outside the perigastric area (D2). The standard curative resection in the United States is gastrectomy plus D0 (sampling without formal node dissection) or D1 lymphadenectomy compared with gastrectomy plus D2 lymphadenectomy in Japan. ⋯ Studies suggest that para-aortic lymphadenectomy (D3) for gastric cancer should be considered experimental, but postoperative regional radiation plus chemotherapy significantly reduces relapse risk and improves survival, and should be considered for all patients except those with D2 resection at high risk for recurrence of gastric cancer who have undergone curative resection. One of the key issues that still has to be addressed is whether chemoradiotherapy will benefit survival or loco regional control in the case of optimal surgery with an over D lymphadenectomy (>or=15 lymph nodes removed) and without splenectomy. This will be addressed in a European randomized clinical trial.
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Most patients with advanced ovarian cancer achieve a clinical complete remission following cytoreductive surgery and chemotherapy with paclitaxel plus carboplatin. However, a majority of these patients will ultimately recur, and second-line treatment for this group of patients is an important aspect of management of this disease as well as an area of active clinical investigation. Until recently, for patients with platinum-sensitive ovarian cancer (more than 6-month disease-free interval), chemotherapy with single-agent carboplatin was frequently recommended. ⋯ One trial compared treatment with paclitaxel plus a platinum compound with re-treatment with platinum, and a second trial compared carboplatin plus gemcitabine re-treatment against carboplatin in patients with platinum-sensitive recurrent ovarian cancer. Both trials showed a 3-month improvement in progression-free survival in patients treated with the combination, as well as acceptable toxicity. In the absence of a prospective randomized trial comparing these two regimens in patients with platinum-sensitive recurrent ovarian cancer, the choice of which combination to use may depend on toxicity considerations.