Ghanta V K, Cohen H J, Silberman H R, Durant J R, Hiramoto R N
Cancer Clin Trials. 1981;4(2):135-41.
A current southeastern cancer study group protocol for the treatment of multiple myeloma involves induction with BCNU, cyclophosphamide, and prednisone (BCP) and maintenance with either melphalan and prednisone (MP), prednisone, Adriamycin, imuran, and vincristine (PAIV), or delayed treatment of relapsed cases following induction. These combinations of drugs are used as induction regimens to establish their chemotherapeutic effects and hematological toxicity in the murine MOPC 104E plasmacytoma model. The three combinations of drugs produce rapid, reliable, and reproducible tumor regressions. However, MP is the only combination which consistently gives long-term disease-free survivors. This particular regimen has least toxicity and is considered to be most effective. BCP produces complete remission with no relapses; however, long-term survivors are not observed with this combination due to early deaths because of drug toxicity. Most of the mice on the PAIV regimen die due to drug toxicity. This combination is considered least effective. With the different drug regimens, toxic events and regressions are noted to occur at different time periods, indicating that perhaps tumor cells in different stages are being destroyed. Toxic events as measured by hematocrit and body weight changes always precede regression by several days. This disparity between rapid drug effects on the host and a delayed effect on the tumor remains unexplained but may possibly be used to advantage in designing future trials.
当前东南癌症研究小组治疗多发性骨髓瘤的方案包括使用卡氮芥、环磷酰胺和泼尼松(BCP)进行诱导治疗,以及使用美法仑和泼尼松(MP)、泼尼松、阿霉素、硫唑嘌呤和长春新碱(PAIV)进行维持治疗,或者对诱导治疗后复发的病例进行延迟治疗。这些药物组合被用作诱导方案,以在小鼠MOPC 104E浆细胞瘤模型中确立其化疗效果和血液学毒性。这三种药物组合均可产生快速、可靠且可重复的肿瘤消退。然而,MP是唯一能持续产生长期无病生存者的组合。这种特定方案毒性最小,被认为是最有效的。BCP可产生完全缓解且无复发;然而,由于药物毒性导致早期死亡,该组合未观察到长期生存者。PAIV方案中的大多数小鼠因药物毒性死亡。这种组合被认为效果最差。采用不同的药物方案时,毒性事件和肿瘤消退在不同时间段出现,这表明不同阶段的肿瘤细胞可能正在被破坏。通过血细胞比容和体重变化衡量的毒性事件总是在肿瘤消退前几天出现。药物对宿主的快速作用与对肿瘤的延迟作用之间的这种差异尚无法解释,但可能在设计未来试验时被加以利用。