Gill P S, Espina B M, Muggia F, Cabriales S, Tulpule A, Esplin J A, Liebman H A, Forssen E, Ross M E, Levine A M
Department of Medicine, Kenneth Norris Cancer Hospital and Research Institute, University of Southern California School of Medicine, Los Angeles 90033, USA.
J Clin Oncol. 1995 Apr;13(4):996-1003. doi: 10.1200/JCO.1995.13.4.996.
Since liposomal encapsulation of anticancer drugs may enhance antitumor activity while reducing toxicity in vitro, we evaluated liposomally encapsulated daunorubucin (DaunoXome; Vestar, Inc, San Dimas, CA) for safety, pharmacokinetics, and potential efficacy in patients with AIDS-related Kaposi's sarcoma (AIDS-KS).
Forty patients with advanced AIDS-KS were accrued. Successive cohorts received DaunoXome at doses of 10, 20, 30, and 40 mg/m2 given once every 3 weeks, and 40, 50, and 60 mg/m2 given once every 2 weeks. Selected KS and solid-tumor patients underwent pharmacokinetic evaluation.
The area under the plasma concentration curve (AUC) ranged from 16.9 micrograms.h/mL to 375.3 micrograms./mL and the alpha half-life ranged from 7.8 to 8.3 hours at 10 mg/m2 to 60 mg/m2, respectively. Both pharmacokinetic profiles were significantly better compared with free daunorubicin. DaunoXome was well tolerated with no significant alopecia, mucositis, or vomiting. Neutropenia (< 1,000/microL occurred in 17% of cycles and was severe (< 500/microL) in only 2%. Anemia and thrombocytopenia were uncommon. Other adverse events included mild to moderate fatigue, nausea, and diarrhea. Even after cumulative doses greater than 1,000 mg/m2, no significant declines in cardiac function were observed. Twenty-two patients who received 50 and 60 mg/m2 were assessable for tumor response; 12 (55%) had a partial response (PR) or clinical complete response (CR). The median survival duration in all patients was 9 months. Prognostic factors for short survival were low CD4 lymphocyte counts (P = .004) and prior anthracycline therapy (P = .02).
DaunoXome has an improved pharmacokinetic profile compared with free daunorubicin, and is well tolerated. DaunoXome can be given safely at doses up to 60 mg/m2 every 2 weeks and has significant antitumor activity in patients with AIDS-KS.
由于抗癌药物的脂质体包封在体外可能增强抗肿瘤活性并降低毒性，我们评估了脂质体包封的柔红霉素（DaunoXome；Vestar公司，加利福尼亚州圣迪马斯）在艾滋病相关卡波西肉瘤（AIDS-KS）患者中的安全性、药代动力学和潜在疗效。
招募了40例晚期AIDS-KS患者。连续队列每3周接受一次剂量为10、20、30和40mg/m²的DaunoXome，以及每2周接受一次剂量为40、50和60mg/m²的DaunoXome。选定的KS和实体瘤患者接受了药代动力学评估。
血浆浓度曲线下面积（AUC）范围为16.9μg·h/mL至375.3μg/mL，α半衰期在10mg/m²至60mg/m²时分别为7.8至8.3小时。与游离柔红霉素相比，两种药代动力学特征均明显更好。DaunoXome耐受性良好，无明显脱发、粘膜炎或呕吐。中性粒细胞减少（<1000/μL）发生在17%的周期中，严重中性粒细胞减少（<500/μL）仅占2%。贫血和血小板减少不常见。其他不良事件包括轻度至中度疲劳、恶心和腹泻。即使累积剂量大于1000mg/m²后，也未观察到心脏功能有明显下降。22例接受50和60mg/m²剂量的患者可评估肿瘤反应；12例（55%）有部分反应（PR）或临床完全缓解（CR）。所有患者的中位生存时间为9个月。生存时间短的预后因素是低CD4淋巴细胞计数（P = 0.004）和先前的蒽环类药物治疗（P = 0.02）。
与游离柔红霉素相比，DaunoXome具有改善的药代动力学特征，且耐受性良好。DaunoXome每2周以高达60mg/m²的剂量安全给药，对AIDS-KS患者具有显著的抗肿瘤活性。
