Susnjar S, Vasović S, Nesković-Konstantinović Z, Stamatović L, Lukić V, Colaković S, Mitrovic L, Jelić S, Radulović S
Department of Medical Oncology, Institute for Oncology and Radiology of Serbia, Belgrade, Yugoslavia.
Tumori. 1999 Nov-Dec;85(6):478-82. doi: 10.1177/030089169908500610.
Twenty-two anthracycline-resistant advanced breast cancer patients were entered from June 1995 till November 1997 in a phase II study to assess the activity and tolerability of second-line chemotherapy consisting of mitoxantrone, 5-fluorouracil and low-dose leucovorin.
Patients were eligible if they failed to respond to doxorubicin-containing chemotherapy, given as first-line chemotherapy for metastatic disease. Treatment consisted of mitoxantrone, 12 mg/m2 iv infusion on day 1, and leucovorin, 50 mg iv 1 hr before 5-fluorouracil, 350 mg/m2 iv infusion on days 1-3, every three weeks.
Nineteen patients were eligible for response, 2 refused further therapy after 2 cycles, and 1 was excluded because grade 3 myelotoxicity developed during the first cycle. Partial remission of 15 months duration occurred in 1 patient, in 7/19 women disease remained stable with a median duration of 11 months (range, 5-24), and 11/19 patients experienced progressive disease. Median time to disease progression was 2 months (range, 0-17), and median survival was 8 months (range, 0-24). Toxicity was generally mild and acceptable. One patient was excluded because of grade 3 granulocytopenia and thrombocytopenia, and one due to cardiotoxicity assessed by the drop of left ventricular ejection fraction to more than 20% below the initial value.
In spite of the very low objective response rate, almost one-fourth of our anthracycline-resistant patients achieved a disease stabilization of 27 weeks duration during mitoxantrone-based second-line chemotherapy. Hence, mitoxantrone in combination with 5-fluorouracil, especially continuous infusion, should be further investigated in this setting, particularly if new and expensive drugs, considered the most active, are not readily available.
1995年6月至1997年11月，22例蒽环类耐药晚期乳腺癌患者进入一项II期研究，以评估由米托蒽醌、5-氟尿嘧啶和低剂量亚叶酸组成的二线化疗的活性和耐受性。
如果患者对含阿霉素的化疗无反应，作为转移性疾病的一线化疗，则符合入组条件。治疗方案为米托蒽醌，第1天静脉输注12mg/m²，亚叶酸，在5-氟尿嘧啶前1小时静脉注射50mg，5-氟尿嘧啶，第1 - 3天静脉输注350mg/m²，每三周一次。
19例患者符合疗效评估条件，2例在2个周期后拒绝进一步治疗，1例因在第1周期出现3级骨髓毒性而被排除。1例患者出现持续15个月的部分缓解，7/19的女性疾病稳定，中位持续时间为11个月（范围5 - 24个月），11/19的患者疾病进展。疾病进展的中位时间为2个月（范围0 - 17个月），中位生存期为8个月（范围0 - 24个月）。毒性一般较轻且可接受。1例患者因3级粒细胞减少和血小板减少被排除，1例因左心室射血分数下降超过初始值的20%而被评估为心脏毒性。
尽管客观缓解率很低，但我们几乎四分之一的蒽环类耐药患者在基于米托蒽醌的二线化疗期间疾病稳定达27周。因此，米托蒽醌联合5-氟尿嘧啶，尤其是持续输注，应在这种情况下进一步研究，特别是在没有最有效的新的昂贵药物时。
