Translation, Validation, and Norming of the Dutch Language Version of the SF-36 Health Survey in Community and Chronic Disease Populations

Angiogenesis is a hallmark of wound healing, the menstrual cycle, cancer, and various ischemic and inflammatory diseases. A rich variety of pro- and antiangiogenic molecules have already been discovered. Vascular endothelial growth factor (VEGF) is an interesting inducer of angiogenesis and lymphangiogenesis, because it is a highly specific mitogen for endothelial cells. Signal transduction involves binding to tyrosine kinase receptors and results in endothelial cell proliferation, migration, and new vessel formation. In this article, the role of VEGF in physiological and pathological processes is reviewed. We also discuss how modulation of VEGF expression creates new therapeutic possibilities and describe recent developments in this field.

Vascular Endothelial Growth Factor and Angiogenesis

The most comprehensive survey of clinical success rates across the drug industry to date shows productivity may be even lower than previous estimates.

Clinical development success rates for investigational drugs.

Purpose To update the International Society of Geriatric Oncology (SIOG) 2005 recommendations on geriatric assessment (GA) in older patients with cancer. Methods SIOG composed a panel with expertise in geriatric oncology to develop consensus statements after literature review of key evidence on the following topics: rationale for performing GA; findings from a GA performed in geriatric oncology patients; ability of GA to predict oncology treatment–related complications; association between GA findings and overall survival (OS); impact of GA findings on oncology treatment decisions; composition of a GA, including domains and tools; and methods for implementing GA in clinical care. Results GA can be valuable in oncology practice for following reasons: detection of impairment not identified in routine history or physical examination, ability to predict severe treatment-related toxicity, ability to predict OS in a variety of tumors and treatment settings, and ability to influence treatment choice and intensit...

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International Society of Geriatric Oncology Consensus on Geriatric Assessment in Older Patients With Cancer

The most significant recent advances in the application of monoclonal antibodies (mAbs) to oncology have been the introduction and approval of bevacizumab (Avastin), an anti-vascular endothelial growth factor antibody, and of cetuximab (Erbitux), an anti-epidermal growth factor antibody. In combination with standard chemotherapy regimens, bevacizumab significantly prolongs the survival of patients with metastatic cancers of the colorectum, breast and lung. Cetuximab, used alone or with salvage chemotherapy, produces clinically meaningful anti-tumor responses in patients with chemotherapy-refractory cancers of the colon and rectum. In addition, the anti-HER2/neu antibody trastuzumab (Herceptin), in combination with standard adjuvant chemotherapy, has been shown to reduce relapses and prolong disease-free and overall survival in high-risk patients after definitive local therapy for breast cancer. These exciting recent results provide optimism for the development of mAbs that bind novel targets, exploit novel mechanisms of action or possess improved tumor targeting. Progress in the clinical use of radioimmunoconjugates remains hindered by complexity of administration, toxicity concerns and insufficiently selective tumor targeting.

Monoclonal antibody therapy of cancer

Proceedings of the American Society of Clinical Oncology

The results of chemotherapy for patients with advanced adenocarcinoma of the small bowel treated at U. T. M. D. Anderson Hospital between 1950 and 1980 were analyzed. A total of 21 single-agent and multidrug chemotherapy regimens were given to 14 patients. 5-Fluorouracil, Adriamycin, mitomycin C, and nitrosourea compounds were the most commonly used chemotherapeutic agents. Fluoropyrimidines, used alone or in combination with the other agents mentioned above, resulted in objective tumor regression in 3 patients (1 partial and 2 minor responses); while 9 additional patients had stable disease. The partial response (PR) was obtained with ftorafur in a patient with supraclavicular lymphadenopathy and hepatic metastasis. Median duration of survival for patients treated with chemotherapy was 9 months. Results of this study show that adenocarcinoma of the small bowel appears to be somewhat less responsive to chemotherapeutic agents than adenocarcinoma arising in the stomach, as reported in the literature. Systematic evaluations of the efficacy of new antitumor agents is indicated to improve results of treatment for advanced small bowel adenocarcinomas.

Chemotherapy for primary adenocarcinoma of the small bowel

During the phase I clinical trial of a new antitumor agent, bruceantin, the pharmacology was studied in 18 cancer patients. The drug was infused intravenously (IV) for 3 h at doses ranging from 1 to 3.6 mg/m2 per day for 5 days. The plasma drug disappearance curves were biphasic, with a fast initial half-life of less than 15 min. The second half-life (t1/2 beta) varied from 0.7 to 38 h among different patients and was not dose-related. The difference between the t1/2 beta on day 1 and that on day 5 was not significant. In patients with normal liver function, the mean plasma concentration at the end of infusion was 22 ng/ml, and the value of the area under the concentration X time curve (AUC) was 111 (ng/ml)h. In contrast, in patients with abnormal liver function the corresponding values were 115 ng/ml and 830 (ng/ml)h, respectively. In addition, these patients had a slower elimination half-life of 10.9 h and a decreased total clearance of 157 ml/min/m2, as compared with 2.6 h and 671 ml/min/m2, respectively, for the normal group. All these differences were statistically significant. Patients with abnormal liver function developed more severe toxicity, including fever, severe nausea, vomiting, and hypotension. Two patients with severe hepatic dysfunction received a reduced dose and developed no toxicity. These results demonstrated the importance of the effects of liver dysfunction on drug disposition and showed that the dosage should be reduced in patients with hepatic dysfunction.

Agop Y. Bedikian

Papers

Proceedings of the American Society of Clinical Oncology

Chemotherapy for primary adenocarcinoma of the small bowel

Clinical pharmacology of bruceantin by radioimmunoassay

Clinical pharmacology of 2,5′-diaziridinyl-3,6-biscarboethoxyamino-1,4-benzoquinone (AZQ)☆