Gan to kagaku ryoho. Cancer & chemotherapy
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STI571 selectively inhibits the ABL-tyrosine kinase, the activity of which is activated by the formation of chimeric BCR/ABL. A phase I study in the USA showed STI571 to be remarkably effective in cases of interferon-refractory chronic myeloid leukemia, with almost no adverse effects. STI571 may become the first choice drug prior to stem cell transplantation and interferon treatment.
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Gan To Kagaku Ryoho · Dec 2000
Review[New guidelines to evaluate the response to treatment "RECIST"].
Response evaluation criteria in solid tumors (RECIST) guidelines proposes the simplification of response evaluation through the use of unidimensional measurements and the sum of the longest diameters for all target lesions. Data from collaborative studies, including more than 4,600 patients assessed for tumor response, support the simplification of response evaluation through the use of unidimensional measurements in stead of the conventional method using two measurements and the sum of the products. In this criteria, PR is at least a 30% decrease and PD is at least a 20% increase in the sum of the longest diameter of target lesions. ⋯ But, in this criteria, there are some problems in Japanese studies. One of them is that we cannot use the endoscopic findings for the evaluation of gastric cancer except for validation purposes, and one is that long NC (long SD) on breast cancer does not exist in this response criteria. We had discussed these problems at the 38th meeting of Japan Society of Clinical Oncology.
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There are no guidelines for dose escalation methods of combination chemotherapy. Thus, in order to evaluate this method, we selected 30 reports on two drug combination chemotherapies without support by BMT, that were published in the Journal of Clinical Oncology from 1997 to 1999. The present report describes the starting dose, patient number at each dose level, or dose escalation method in these 30 papers.
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To reduce the number of patients treated at low and biologically inactive doses in phase I trials of anticancer agents, attempts to decrease the number of patients per dose level and to conduct a larger dose escalation have been made. Among them, accelerated titration designs were proposed and evaluated by simulation; designs 2 and 4 were reported to be acceptable (J Natl Cancer Inst 89: 1138-1147, 1997). Both designs 2 and 4 included only one patient per cohort during the initial accelerated phase. ⋯ Decision-making on dose escalation based on the information on toxicity in three courses might be cumbersome. Therefore, in Japan, design 2 would be recommended among the proposed accelerated designs. The performance of the design should be investigated by applying it to actual phase I studies and by evaluating the number of undertreated and overtreated patients.
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We discuss the basic concept of the continual reassessment method (CRM) and some modifications. The CRM has been proposed as alternatives of traditional cohort design for phase I trials in cancer. ⋯ Then, CRM is introduced so that the essential feature is in the sequential (continual) selection of a dose level for next patients based on the dose-toxicity relationship and in updating the relationship based on patients' response date using Bayesian calculation. Finally we discuss both advantages and pitfalls in practice.