After 20 years of effort, in recent years, studies have shown that Judah Folkman in 1971 proposed the concept of "long-term anti-angiogenesis drug grant will enable the long-term maintenance of malignant tumors in the rest (dormancy) condition is not deteriorating," is correct. Boehm, such as when in 1997 to animal experiments show that different from chemotherapy drugs endoxan will trigger the use of the drug-resistant tumor cells, but only short-term inhibition of tumor growth, long-term intermittent use endostatin (one body of the anti-angiogenesis material), can lead to a small rat allograft tumor removed completely.
The results of this exciting cancer a basic research staff, clinical medical staff, cancer patients and their families and the medical community who do. Many research and development of new drugs are targeted at a "angiogenesis," as the goal. According to Angiogenesis Foundation database of clinical trials in April 2001 on the statistics, China currently under the first phase of clinical trials of anti-angiogenesis drugs are 31 kinds, for the second phase of clinical trials, and there are 32 kinds of drugs , and another 12 kinds of (new and old drugs) were carried out in Phase III clinical trials, the result of the majority of anti-angiogenic drugs on the mechanism of inhibition was considered mainly neovascularization of the newborn, but it will not have been caused by the existence of a mature ( mature) vascularized dissipated, so they may only be considered to maintain the same tumor regression of large or slow (regression); while unlikely to lead to tumor rapid, obvious decrease. Therefore, the anti-angiogenesis drug cytostatic drugs should be. Because of their role in a manner different from the past of anti-cancer chemotherapy drugs (a cytotoxic drug), anti-angiogenesis drugs in clinical trial drug research and development
Indeed inspection encountered some trouble. Because the majority of cancer clinical trials of norms is in response to the development of chemotherapy drugs established. For example, the use of chemotherapy drugs is the rule of a higher dose of better efficacy, it should be possible, using the maximum tolerated dose. Therefore, the first phase of clinical trials, the main purpose was to observe the dose-limiting toxicity of drugs (dose-limiting toxicity) and patients the highest tolerated dose (maximal tolerable dose), however, anti-angiogenesis drug side effects is different from that of chemical treatment Acute side effects are sometimes not significant, there is no one will be able to observe the acute dose limiting toxicity or the patient the maximum tolerated dose, Furthermore, anti-angiogenesis drug use "maximum" tolerated dose, not necessarily is the "best" Health
Activity dose. This makes anti-angiogenesis drug, the first phase of the need for clinical trials has been questioned.
In the second phase of clinical trials, the majority of chemotherapy drugs could not be ascertained due to its possible treatment
Efficiency, are a single drug for the treatment of the subject For tumors of the second-line treatment for the beginning, if these can be about 20% of the tumor response rate, are considered to be effective and to carry out the next stage of clinical trials. However, anti-angiogenesis drugs because of their role and not be good can lead to rapid tumor remission, but only to maintain the same tumor, and it is in anti-angiogenesis drug, the second phase of clinical trials will not be able to tumor response rate to assess its efficacy, while its general will take into account non-tumor survival or remission rate of tumor markers (tumor progression-free survival or tumor-marker response rate). However, the "survival of tumor-free period" or "tumor
Remission rate of signs "as the effects of the indicators, the absence of appropriate control group existed, but also difficult to compare the subjects of anti-angiogenesis drugs really can effectively prevent the deterioration of the tumor to extend the" no tumor survival "or reduce the value of tumor markers, or because the choice of cases caused by the impact. because in the clinical trial design Indeed, the need for the control group and non-tumor survival as an index, so in the design of the above must go directly to the first phase were randomly divided into three Clinical Trials Group in order to verify that anti-angiogenesis drugs on the extension of non-tumor effect of survival.
The second phase of clinical trial design, usually the use of randomized design, comparison of anti-angiogenesis drug chemotherapy combined existing prescription of whether it can be effectively used alone to improve the efficacy of chemotherapy prescription (an increase of tumor response rate). If this second phase randomized clinical trial found or confirmed the merger of anti-angiogenesis drugs can effectively improve the chemotherapy drugs on the efficacy of a particular tumor, it can enter phase III randomized trial to verify that anti-angiogenesis drug use to improve the tumor response rate is to further improve the overall survival rate of patients (overall survival).
In recent years, there is a growing a number of anti-angiogenesis drug, the second phase of clinical trial results are
Published on the results, do not see clearly because of the tumor to alleviate the effect of some academics and patients feel very discouraged, but we still believe that good design can only wait for clinical trials to choose the appropriate drugs out the first randomized three-phase clinical trial results, we can really know these drugs in the treatment of cancer of the true value of the above.
Moreover, with the cumulative clinical trials and laboratory technology, striving to excel, there are now evidence to suggest that anti-angiogenesis therapy, not as in the past there will be no recognition of the problem of drug-resistant. Heterogeneity of tumor cells (heterogeneity) in addition to general knowledge of the capacity of resistance to chemical drugs, but also includes the degree of interdependence of vascular heterogeneity or induced angiogenesis mechanism of heterogeneity (heterogeneity in vascular-dependence and angiogenic pathway) Therefore, anti-angiogenesis drug use in the future will also be towards the compound of anti-angiogenesis drug therapy (combination anti-angiogenic agents therapy) and in combination with other treatment methods, such as surgery, radiation therapy or even a combination of chemical treatment to prevent or delay the emergence of a anti-angiogenesis cancer drug production, and to have better efficacy.
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