Kimura I, Ohnoshi T, Hiraki S, Ueoka H, Toyata K, Miyamoto H, Yamane T, Ueno K, Murashima M
Gan No Rinsho. 1985 May;31(6 Suppl):767-73.
Mitoxantrone is an anthracenedione with structural similarities to adriamycin but without the amino-sugar moiety on the parent molecule. The compound attracted attention on the basis of animal tumor studies in which it showed equal or superior efficacy compared to adriamycin, but with diminished cardiotoxicity; and it was not fully cross-resistant to adriamycin. Our in vitro studies using human small cell lung cancer cell line (SBC-3) disclosed the absence of cross-resistance between mitoxantrone and adriamycin: SBC-3/ADM, which had developed resistance by continuous exposure to increasing concentration of adriamycin, was as equally sensitive to mitoxantrone as SBC-3 was when tested by clonogenic assay. A phase II study conducted in our Department revealed that mitoxantrone was active to malignant lymphoma refractory to conventional agents including adriamycin: 6 (33%) of 18 patients responded to the agent. Based on the results of our phase II studies of mitoxantrone, etoposide, and cisplatin in malignant lymphoma, we have conducted a phase III study of a 4-drug combination of these 3 drugs plus prednisolone in relapsed or refractory lymphoma: Out of 14 patients, 3 responded completely and 4 did partially, so far. The regimen would appear useful as a salvage therapy for refractory lymphoma.
米托蒽醌是一种蒽二酮，其结构与阿霉素相似，但母体分子上没有氨基糖部分。该化合物在动物肿瘤研究中受到关注，在这些研究中，它显示出与阿霉素相当或更高的疗效，但心脏毒性降低；并且它与阿霉素并非完全交叉耐药。我们使用人小细胞肺癌细胞系（SBC - 3）进行的体外研究表明，米托蒽醌与阿霉素之间不存在交叉耐药性：通过持续暴露于浓度递增的阿霉素而产生耐药性的SBC - 3/ADM，在克隆形成试验中测试时，对米托蒽醌的敏感性与SBC - 3相同。我们科室进行的一项II期研究表明，米托蒽醌对包括阿霉素在内的常规药物难治的恶性淋巴瘤有活性：18例患者中有6例（33%）对该药物有反应。基于我们对米托蒽醌、依托泊苷和顺铂在恶性淋巴瘤中的II期研究结果，我们对这3种药物加泼尼松龙的4药联合方案在复发或难治性淋巴瘤中进行了III期研究：到目前为止，14例患者中有3例完全缓解，4例部分缓解。该方案似乎可作为难治性淋巴瘤的挽救治疗方法。
