VP-16 in advanced soft tissue sarcoma: a phase II study of the EORTC soft tissue and bone sarcoma group.
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Biomedical subjects
Publications and source records attributed to H Mouridsen.
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The initial biochemical data (serum[S]-carcinoembryonic antigen, S-lactate dehydrogenase, S-gammaglutamyl transferase, S-alkaline phosphatase urine[U]-creatinine, and three urinary quantities related to collagen metabolism) and surgical pathology data (tumor size, grade of tumor anaplasia, number of positive lymph nodes, number of negative lymph nodes) were examined in 52 consecutive postmenopausal risk group II patients operated for primary breast cancer without metastatic disease (mastectomy + partial axillary resection) who participated in the Danish Breast Cancer Group's controlled clinical trial of radiation (RT) alone, and RT + levamisol. The follow-up (mean = 3.45 years, range = 3-4 years) included physical examination every three months, x-ray of chest, bone scan, and x-ray of axial skeleton every six months. Recurrence was defined as metastatic disease detected during the first three years of postoperative follow-up study. Twenty patients had recurrences. A stepwise discriminant analysis of the surgical pathology quantities showed that all quantities except tumor size contributed significantly (P less than 0.01) to the discrimination between controls (no recurrence after 3-4 years) and patients who had recurrences within three years. When each of the biochemical quantities was combined with the surgical pathology data it was found that only urinary total hydroxy-proline to creatinine ratio improved the discrimination significantly (P less than 0.05) and that the effect was marginal.
We followed the cases of 26 consecutive postmenopausal patients operated on for primary breast cancer. Serum specimens were obtained each month for 1.5 years and stored at -80 degrees C until assayed for carcinoembryonic antigen (CEA) and other quantities. Ten patients developed recurrence, while 16 qualified as controls (no clinical recurrence for at least 1.7 years after the last venipuncture). Using the homeostatic autoregressive time series model, modified by us to be particularly sensitive to sustained deviations from the mean, we detected four recurrences by CEA without having any falsely positive alarms. Group-based reference limits and application of the unmodified homeostatic model were less effective (fewer detected and shorter lead time). Simulation studies, involving use of a mathematical model relating CEA concentration to tumor growth and using parameters estimated from patient data, verified this and indicated that at least five stable baseline values are needed to detect 100% of recurrences before they are detected by the group-based limit.
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The randomized clinical trial is a scientific method for solving clinical problems. The method is typically employed before a new type of treatment is offered on a major scale in order to safeguard patients against a less curative therapy. Especially with regard to cancer treatment, randomized studies are conducted in increasing numbers. However, there remains a considerable discrepancy between the actual number of patients entered in randomized trials and the eligible number available. The demand of obtaining informed consent is a major reason for not entering patients into randomized studies. The critical item is whether information about randomization as a method for allocation should be disclosed to the patient. The doctor feels embarrassed not to be able to advise and support the patient in decision making about treatment and finds his or her role as the caring doctor replaced by the roulette. The requirement to seek informed consent has increased the rate of denial to participate in randomized trials from a few percent, up to about 50% or even higher.