Schiefer D, Gottstein C, Diehl V, Engert A
Klinik I für Innere Medizin, Universität zu Köln.
Med Klin (Munich). 1999 Oct 15;94(10):570-9. doi: 10.1007/BF03044955.
The overall mortality due to metastatic cancer has not or only minimally been reduced in spite of intensive research and many innovations in the field of conventional antineoplastic therapy in the past decade. In the last years it has become a fact that tumor growth is angiogenesis-dependent. Therefore, inhibitors of angiogenesis are a new class of antineoplastic substances with a novel mechanism of action that might be a powerful complement to conventional cytostatic therapy. SUBSTANCES AND CLINICAL TRIALS: Inhibitors of tumor-angiogenesis which have entered clinical trials, with their results published until December 1998 are discussed here. Most results originate from phase-I or phase-II clinical trials. They are discussed and compared in respect to toxicity and response. Also some substances with high therapeutic potential which are still in preclinical testing are discussed.
Many of the investigated angiogenesis inhibitors demonstrated anti-tumor effects in phase-I or phase-II clinical trials. The commonest manifestation was stable disease, followed by partial remissions. In a few cases, complete remissions were observed. The toxicities of these substances differ both in type and degree of side effects.
Some antiangiogenic drugs appear to be promising candidates for a clinical use in the therapy of solid tumors. Further conclusions can only be drawn after evaluation of the results of ongoing phase-III clinical trials.
尽管在过去十年里,传统抗肿瘤治疗领域进行了深入研究并取得了诸多创新,但转移性癌症导致的总体死亡率并未降低或仅有轻微下降。近年来,肿瘤生长依赖血管生成已成为事实。因此,血管生成抑制剂是一类新型抗肿瘤物质,其作用机制新颖,可能是传统细胞毒性治疗的有力补充。
本文讨论了已进入临床试验且截至1998年12月已发表结果的肿瘤血管生成抑制剂。大多数结果来自I期或II期临床试验。从毒性和反应方面对它们进行了讨论和比较。还讨论了一些仍处于临床前测试阶段、具有高治疗潜力的物质。
许多研究的血管生成抑制剂在I期或II期临床试验中显示出抗肿瘤作用。最常见的表现是病情稳定,其次是部分缓解。在少数情况下,观察到完全缓解。这些物质的毒性在副作用的类型和程度上均有所不同。
一些抗血管生成药物似乎有望用于实体瘤治疗的临床应用。只有在对正在进行的III期临床试验结果进行评估后,才能得出进一步结论。