Seminars in oncology
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Seminars in oncology · Dec 2005
Comparative StudyOverview of adjuvant therapy for resected gastric cancer: differences in Japan and the United States.
Survival in adjuvant chemotherapy following resected gastric cancer has been studied by both Japanese and Western investigators using varied chemotherapy regimens in different target patients. Gastrectomy with D2 lymphadenectomy is the standard in Japan, and trials of adjuvant therapy in these patients have shown no survival advantages over surgery alone. In the United States, where 5-year survival rates in patients with gastric cancer are much lower following potentially curative surgery, adjuvant therapy has shown a survival benefit. ⋯ The Japanese viewpoint on the use of adjuvant therapy in patients with gastric cancer following potentially curative resection is that the quality of surgery, including diagnostic and pathologic procedures, is a more important prognostic factor than adjuvant chemotherapy. Also, they have determined from previously conducted clinical trials that patients with stage 1-2 tumors should be excluded from the target populations of randomized trials. Until the results of INT-0116 became available, there had been no improvement, or only marginal improvement, in overall or disease-free survival for patients receiving adjuvant chemotherapy following gastric cancer resection in the United States and Europe.
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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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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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Seminars in oncology · Dec 2005
ReviewFront-line therapy for advanced colorectal cancer: emphasis on chemotherapy.
For four decades, 5-fluorouracil was the only option available for patients with metastatic colorectal cancer. It provided a response rate of 15% to 20%, with a median survival of approximately 1 year. ⋯ Use of two to three lines of combination therapies has raised the median survival to almost 2 years. New and promising targeted and cytotoxic therapies are currently being studied and will ideally continue to extend the median survival as well as improve the quality of life of patients with colorectal cancer.
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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.