Markman M, George M, Hakes T, Reichman B, Hoskins W, Rubin S, Jones W, Almadrones L, Lewis J L
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
J Clin Oncol. 1990 Jan;8(1):146-50. doi: 10.1200/JCO.1990.8.1.146.
To define both the toxicity and efficacy of intraperitoneal mitoxantrone in the treatment of refractory ovarian carcinoma, 31 patients were entered onto a phase II trial of this agent delivered in a 2 L treatment volume on a monthly basis. Due to excessive local pain at the initial dose level (30 mg/m2), the amount of drug delivered with each treatment course was reduced to 20 mg/m2. Despite this reduction, 74% of patients required narcotic analgesia during treatment. In addition, there were four episodes of bowel obstruction (one requiring surgical intervention) during therapy, and two patients developed bowel obstruction and intraabdominal abscesses following the completion of treatment. Six of 18 evaluable patients (33%) whose largest tumor diameter was less than or equal to 1 cm at protocol initiation experienced surgically documented responses, compared with one of 11 patients (9%) whose largest tumor was greater than 1 cm in diameter. If the two patients exhibiting what we called a mixed response to treatment are included, seven of 21 patients previously treated with intraperitoneal cisplatin responded to this treatment program, including four patients who had failed to respond to intraperitoneal cisplatin. No responding patient has demonstrated clinical evidence of relapse with a median follow-up of 7 months (range, 3+ to 13+ months) from response laparotomy. Intraperitoneal mitoxantrone is an active treatment program in patients with small-volume refractory ovarian carcinoma, but local toxicity can be severe. Due to the toxicity encountered with this specific program, its use cannot be recommended for standard clinical practice. However, in view of the activity observed in refractory ovarian carcinoma, including responses in patients who had previously failed intraperitoneal cisplatin, it is important to continue to explore alternative therapeutic regimens using intraperitoneal mitoxantrone to reduce local toxicity while maintaining or improving efficacy.
为明确腹腔内米托蒽醌治疗难治性卵巢癌的毒性和疗效，31例患者进入该药物的II期试验，每月在2L治疗容积下给药。由于初始剂量水平（30mg/m²）时局部疼痛过度，每个疗程的给药量减至20mg/m²。尽管剂量降低，但74%的患者在治疗期间需要使用麻醉性镇痛药。此外，治疗期间发生了4例肠梗阻（1例需要手术干预），2例患者在治疗结束后出现肠梗阻和腹腔内脓肿。在方案开始时最大肿瘤直径小于或等于1cm的18例可评估患者中，有6例（33%）经历了手术记录的缓解，而最大肿瘤直径大于1cm的11例患者中有1例（9%）缓解。如果将表现出我们所谓的混合治疗反应的2例患者包括在内，21例先前接受腹腔内顺铂治疗的患者中有7例对该治疗方案有反应，包括4例对腹腔内顺铂无反应的患者。从反应性剖腹手术起，中位随访7个月（范围3+至13+个月），无反应患者出现复发的临床证据。腹腔内米托蒽醌是小体积难治性卵巢癌患者的一种有效治疗方案，但局部毒性可能很严重。由于该特定方案存在毒性，不推荐将其用于标准临床实践。然而，鉴于在难治性卵巢癌中观察到的活性，包括先前腹腔内顺铂治疗失败患者的反应，继续探索使用腹腔内米托蒽醌的替代治疗方案以降低局部毒性同时维持或提高疗效很重要。
