分子靶向治疗在淋巴瘤中的应用.ppt

* 2 2 We kno from basic studies in the early 80′s, that 2-CdA is inducing apoptosos in dividing but also in resting cells independent from cell cycle. This observation lead to the idea, that this could be an advantage in the therapy of indolent lymphomas. It is well known that 2-CdA is very effective in the treatment of HCL, inducing very long lasting complete remissions. But 2-Cda has also been demonstrated to be effective in other indolent lymphoproliferative disorders like low-grade NHL, CLL and cutaneous lymphomas and also in relapsed ALL. It was in 1992, that the Group from the Scripps-Clinic in San Diego, and in 1995 also Liliemark and Juliusson demonstrated the efficacy of cladribine in pretreated patients with NHL. However, in these heavily pretreated patients a high rate of severe infectious problems was reported in the range of about 20-40%, probably due to the extensive pretreatment. In 1995, again Saven and Piro from the Scripps Clinic, demonstrated the activity of Cladribine for the first time in untreated indolent NHL. They used the 7-day continous infusion regimen with 0,1 mg/kg/d, which is the approved schedule in the USA using 2-CdA. * 针对CD22抗原的抗体：SM03, Epratuzumab(已完成I/II期临床试验，进入III期） * * * * * * 二十世纪七十年代到八十年代已证实CHOP作为第一代联合化疗方案治疗淋巴瘤的疗效，患者达到较高有效率（45%~53%）和较高长期生存率（五年或五年以上为30%~37%）。 二十世纪八十年代中进行的单中心研究试验提示中高度非霍奇金淋巴瘤患者使用更复杂的第三代方案有55%~65%可能被治愈。 在二十世纪八十年代中，西南癌症协作组（SWOG）和东部癌症协作组（ECOG）进行了前瞻性随机III期临床试验（NHPLS）在侵袭性非霍奇金淋巴瘤患者中比较CHOP方案与几个第三代联合化疗方案的相对疗效。 可评价患者（N=899）由预后因素分层，随机进入四个治疗组接受CHOP,m-BACOP,ProMACE-CytaBOM或MACOP-B方案治疗。 治疗后三年，44%患者无病生存，四个治疗组没有显著差别。然而，CHOP方案治疗的患者很少有致死性毒性反应（P=0.09）。 这些结果确立了侵袭性非霍奇金淋巴瘤患者治疗中CHOP方案作为标准治疗。 * * * * * * * * * * * * 弥漫大B细胞淋巴瘤 分子靶向治疗进展 弥漫大B细胞淋巴瘤治疗中存在问题 Fisher et al. N Engl J Med. 1993;328:1002. 年 患者死亡 3年生存预测 CHOP-21 226 88 54% m-BACOD 223 93 52％ ProMACE-CytaBOM 233 97 50% MACOP-B 218 93