Markman M, Hakes T, Reichman B, Lewis J L, Rubin S, Jones W, Almadrones L, Hoskins W
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
J Clin Oncol. 1991 Jun;9(6):978-82. doi: 10.1200/JCO.1991.9.6.978.
Previous experimental and clinical evaluation has suggested that ovarian cancer is sensitive to the cytotoxic effects of mitoxantrone at concentrations achievable within the peritoneal cavity after intraperitoneal (IP) administration. Unfortunately, the use of the drug delivered IP at high doses (20 mg/m2 in 2 L normal saline [NS]) on a monthly schedule is compromised by severe local effects secondary to the irritant properties of the drug. To reduce toxicity and take advantage of minimal systemic drug exposure following IP administration, we treated 28 patients with a lower drug concentration of mitoxantrone (10 mg/m2 in 2 L NS), but on a weekly or every other week schedule (total, 12 courses). Compared with the monthly program, this regimen caused less pain, allowed for a higher cumulative dose of mitoxantrone to be delivered, and resulted in less serious treatment-related morbidity. Four of 13 assessable patients (31%) whose largest tumor was less than or equal to 1 cm in diameter demonstrated a surgically defined response. All responding patients had failed previously or exhibited a minimal response to cisplatin. Despite the improved toxicity profile of this regimen, the overall response rate was similar to the monthly program, probably secondary to inadequate IP drug distribution in many patients. Future investigative efforts using IP mitoxantrone as therapy for ovarian cancer might focus on developing methods to improve drug delivery to all sites of tumor within the peritoneal cavity (eg, intraoperative therapy, increased treatment volumes, and antiinflammatory agents to reduce adhesion formation).
先前的实验和临床评估表明，卵巢癌对米托蒽醌的细胞毒性作用敏感，腹腔内（IP）给药后腹腔内可达到该浓度。不幸的是，每月一次高剂量（20mg/m²溶于2L生理盐水[NS]）腹腔给药时，由于药物的刺激性导致严重的局部效应，影响了该药物的使用。为了降低毒性并利用腹腔给药后全身药物暴露最小化的优势，我们对28例患者采用较低浓度的米托蒽醌（10mg/m²溶于2L NS）进行治疗，但采用每周或每隔一周给药方案（共12个疗程）。与每月给药方案相比，该方案引起的疼痛较轻，可给予更高的米托蒽醌累积剂量，且治疗相关的严重发病率较低。13例可评估患者中，4例（31%）最大肿瘤直径小于或等于1cm，表现出手术确定的反应。所有有反应的患者之前均治疗失败或对顺铂反应极小。尽管该方案的毒性有所改善，但总体反应率与每月给药方案相似，这可能是由于许多患者腹腔内药物分布不足所致。未来将腹腔内米托蒽醌用于卵巢癌治疗的研究工作可能会集中在开发改善药物向腹腔内所有肿瘤部位递送的方法上（例如，术中治疗、增加治疗体积以及使用抗炎药物减少粘连形成）。
