Shpall E J, Jones R B, Holland J F, Bhardwaj S, Paciucci P A, Wilfinger C L, Strashun A
Department of Medicine, Duke University Medical Center, Durham, NC 27710.
J Natl Cancer Inst. 1988 Apr 6;80(3):204-8. doi: 10.1093/jnci/80.3.204.
Twenty-seven women with metastatic breast cancer were treated with mitoxantrone as a single agent, with the use of an intensive dose-escalating schedule. Doses were given at 0.5 mg/m2/day as an iv injection for 3 consecutive days and then were escalated each month by 2.5 mg/m2/day until maximal tolerance was reached on the basis of hematologic or cardiac toxicity. No complete responses were demonstrated. Six patients (22%) had partial responses of 5.5 months' median duration. Four of 12 patients who had not received prior doxorubicin responded (33%), whereas two of 15 patients with previous doxorubicin exposure responded (13%). Cardiotoxicity, determined by serial radionuclide ventriculography, occurred in 10 patients (37%) at a mean total mitoxantrone dose of 83.0 mg/m2. Three of these 10 patients had no predisposing risk factors, four had received thoracic radiotherapy that might have involved the heart, and three had received prior doxorubicin without clinical toxicity. The failure of dose intensification to augment the response rate when compared to the response rates reported for less myelotoxic doses of the drug, in addition to the extent of cardiotoxicity noted, calls into question the value of dose intensification of mitoxantrone in the treatment of metastatic breast cancer.
27例转移性乳腺癌女性患者接受了米托蒽醌单药治疗，采用强化剂量递增方案。剂量以0.5mg/m²/天静脉注射，连续3天给药，然后每月递增2.5mg/m²/天，直至基于血液学或心脏毒性达到最大耐受剂量。未观察到完全缓解。6例患者（22%）出现部分缓解，中位缓解持续时间为5.5个月。12例未接受过阿霉素治疗的患者中有4例（33%）有反应，而15例曾接受过阿霉素治疗的患者中有2例（13%）有反应。通过连续放射性核素心室造影确定，10例患者（37%）出现心脏毒性，米托蒽醌的平均总剂量为83.0mg/m²。这10例患者中，3例无易感危险因素，4例接受过可能累及心脏的胸部放疗，3例曾接受过阿霉素治疗但无临床毒性。与报道的该药物骨髓毒性较小剂量的缓解率相比，剂量强化未能提高缓解率，此外还观察到心脏毒性的程度，这使人质疑米托蒽醌剂量强化在转移性乳腺癌治疗中的价值。
