Maintenance therapy to suppress micrometastasis: The new challenge for adjuvant cancer treatment
Maintenance therapy to suppress micrometastasis: The new challenge for adjuvant cancer treatment
复制标题
DOI：
10.1158/1078-0432.ccr-05-0437
复制
发表时间：
2005-08-01
影响因子：
11.5
通讯作者：
Epstein, RJ
中科院分区：
文献类型：
--
作者：
Epstein, RJ
使用临床试验中显示的肿瘤缩小（反应）率常规评估细胞毒性药物的姑息疗效。虽然辅助药物治疗具有与姑息治疗不同的目标（即，通过抑制微转移性疾病的进展来延长存活），人们普遍认为药物的辅助功效将与其在疾病晚期的反应率（“活性”）平行。鉴于最近的发展，重新考虑这一假设似乎是及时的：认识到许多短期肿瘤反应的预测因素与长期生存结局呈负相关;肿瘤进展的特征是一个不连续的过程，可能包括休眠期;认识到微转移在治疗上可通过多种机制抑制，包括直接杀死肿瘤细胞，对正常组织的旁分泌生长信号的细胞毒性破坏和对促转移途径的靶向抑制;认识到肿瘤休眠不仅阻断细胞毒性药物的抗转移功效，而且代表转移抑制性非细胞毒性药物如激素抑制剂的治疗终点;以及最佳辅助药物治疗可能包括诱导和维持成分的见解。因此，传统观点认为细胞减灭反应是辅助药物疗效的先决条件，值得重新评估，以期加速将新型非细胞毒性维持治疗纳入对照研究。
The palliative efficacy of cytotoxic drugs is routinely assessed using tumor shrinkage (response) rates shown in clinical trials. Although adjuvant drug therapy has a goal distinct from that of palliative therapy (i.e., to prolong survival by inhibiting progression of micrometastatic disease), it is widely assumed that the adjuvant efficacy of a drug will parallel its response rate ("activity") in advanced stages of the disease. Reconsideration of this assumption seems timely in view of recent developments: the realization that many predictors of short-term tumor response correlate inversely with long-term survival outcomes; the characterization of tumor progression as a discontinuous process that may include dormant phases; the understanding that micrometastasis is therapeutically suppressible by a variety of mechanisms including direct tumor cell kill, cytotoxic disruption of paracrine growth signals from normal tissues, and targeted inhibition of prometastatic pathways; the recognition that tumor dormancy not only blocks the antimetastatic efficacy of cytotoxic drugs but also represents a therapeutic end point for metastasis-suppressive noncytotoxic drugs such as hormone inhibitors; and the insight that optimal adjuvant drug therapy is likely to include both induction and maintenance components. The traditional view of cytoreductive response as a prerequisite for adjuvant drug efficacy thus merits reappraisal, with a view to accelerating incorporation of novel noncytotoxic maintenance therapies into controlled studies.