Chlebowski R T, Bulcavage L, Henderson I C, Woodcock T, Rivest R, Elashoff R
UCLA School of Medicine, Department of Medicine, Torrance 90509.
Breast Cancer Res Treat. 1989 Dec;14(3):267-74. doi: 10.1007/BF01806298.
To determine the safety and efficacy of mitoxantrone use in hyperbilirubinemic breast cancer patients, a prospectively determined dosage schedule was evaluated in a multi-center trial. Pretreatment bilirubin prospectively defined three groups: Controls (with normal bilirubin) and two Study groups (with either moderate or severe bilirubin increase). Bilirubin determined initial mitoxantrone dose as well: bilirubin less than 3.5 mg/dl, 14 mg/m2; and bilirubin greater than or equal to 3.5 mg/dl, 8 mg/m2. Mitoxantrone at 14 mg/m2 was well tolerated in patients with moderate hepatic dysfunction. Patients with severe hepatic dysfunction demonstrated a mixed toxicity picture, with performance status (ECOG level 3) defining a population with limiting myelosuppression and/or early death. The survival of Study patients with severe hepatic dysfunction (median 17 days) was significantly worse than both Control (p less than 0.01) and Study (p less than 0.05) patients with lower bilirubin. Entry performance status (ECOG level 0-2 versus level 3) profoundly influenced survival (median survival 222 days versus 25 days, respectively, p less than 0.0001). Objective responses were seen in patients with both normal and elevated bilirubin. Bilirubin reduction following mitoxantrone commonly occurred, representing at least an indicator of favorable prognosis. Recommendations for mitoxantrone use include: 1. Patients with moderate bilirubinemia tolerate 14 mg/m2 mitoxantrone with reasonable chance for benefit. 2. Patients with severe hepatic dysfunction and poor performance status should not be given mitoxantrone. A definitive recommendation regarding use of reduced 8 mg/m2 mitoxantrone in patients with severe hyperbilirubinemia and favorable performance status requires further study.
为了确定米托蒽醌用于高胆红素血症乳腺癌患者的安全性和有效性，在一项多中心试验中评估了预先确定的给药方案。治疗前胆红素前瞻性地定义了三组：对照组（胆红素正常）和两个研究组（胆红素中度或重度升高）。胆红素也决定了初始米托蒽醌剂量：胆红素低于3.5mg/dl，14mg/m²；胆红素大于或等于3.5mg/dl，8mg/m²。米托蒽醌14mg/m²在中度肝功能不全患者中耐受性良好。重度肝功能不全患者表现出混合毒性情况，体能状态（东部肿瘤协作组3级）定义了一组存在严重骨髓抑制和/或早期死亡的人群。重度肝功能不全的研究患者的生存期（中位数17天）明显短于胆红素水平较低的对照组患者（p<0.01）和研究组患者（p<0.05）。入组时的体能状态（东部肿瘤协作组0 - 2级与3级）对生存期有深远影响（中位生存期分别为222天和25天，p<0.0001）。胆红素正常和升高的患者均可见客观缓解。米托蒽醌治疗后胆红素通常会降低，这至少是预后良好的一个指标。米托蒽醌使用的建议包括：1. 中度胆红素血症患者耐受米托蒽醌14mg/m²且有合理的获益机会。2. 重度肝功能不全且体能状态差的患者不应给予米托蒽醌。对于重度高胆红素血症且体能状态良好的患者使用降低剂量的8mg/m²米托蒽醌的明确建议需要进一步研究。
