Liposomal doxorubicin for the treatment of hormone-refractory prostate cancer.
Liposomal doxorubicin for the treatment of hormone-refractory prostate cancer.
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DOI：
10.3816/cgc.2002.n.005
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发表时间：
2002-06-01
期刊：
影响因子：
--
通讯作者：
Small, Eric J
中科院分区：
文献类型：
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作者：
Harris, Katherine A;Harney, Elaine;Small, Eric J
目前迫切需要新的药物来治疗激素难治性前列腺癌（HRPC）。阿霉素在这种情况下显示出适度的活性，但由于其毒性，其使用受到限制。在某些肿瘤类型中，阿霉素脂质体包封似乎促进了肿瘤的积累，并且毒性似乎降低了。因此，在HRPC患者中进行了一项脂质体阿霉素的II期试验。14例进行性HRPC患者接受治疗。仅在第一次给药时，患者随机接受50mg /m2的阿霉素或50mg /m2的阿霉素脂质体，以评估探索性药代动力学。在随后的所有周期中，所有患者均接受阿霉素50mg /m2脂质体治疗。通过血清前列腺特异性抗原（PSA）的一系列测量和序列成像研究来评估对治疗的反应。所有14例患者的反应和毒性均可评估。2例患者（14%）血清PSA下降>或= 50%。第一位患者的PSA基线为34.7 ng/mL，最低点为17.0 ng/mL。第二例患者的PSA基线为5580.0 ng/mL，最低点为200.7 ng/mL。后者在骨扫描方面有明显的改善，疼痛也减轻了。治疗总体耐受良好。一名患者在第一轮阿霉素脂质体输注出现3级反应后退出治疗。中性粒细胞减少是最常见的毒性；只有1例为3级，未见4级病例。阿霉素血药浓度最适合线性双室模型。阿霉素脂质体血浆浓度最适合线性单室模型。阿霉素脂质体治疗总体耐受良好。虽然阿霉素脂质体单药治疗在HRPC治疗中只有适度的活性，但研究该药物作为联合化疗的一部分可能是有意义的。
There is a pressing need for new agents to treat hormone-refractory prostate cancer (HRPC). Doxorubicin has shown modest activity in this setting, but its use is limited by its toxicities. Liposomal encapsulation of doxorubicin appears to promote enhanced tumor accumulation in some tumor types, and toxicity appears to be reduced. A phase II trial of liposomal doxorubicin was therefore conducted in patients with HRPC. Fourteen patients with progressive HRPC were treated. For the first dose only, patients were randomized to receive either doxorubicin 50 mg/m2 or liposomal doxorubicin 50 mg/m2 in order to evaluate exploratory pharmacokinetics. For all subsequent cycles, all patients received liposomal doxorubicin 50 mg/m2. Response to therapy was assessed with serial measurements of serum prostate-specific antigen (PSA) and sequential imaging studies. All 14 patients were evaluable for response and toxicity. Two patients (14%) had declines in serum PSA of > or = 50%. The first patient had a baseline PSA of 34.7 ng/mL and a nadir of 17.0 ng/mL. The second patient had a baseline PSA of 5580.0 ng/mL and a nadir of 200.7 ng/mL. The latter of these 2 patients had an unambiguous improvement in bone scan and a reduction in pain. Treatment was well tolerated overall. One patient was removed from treatment after the development of a grade 3 infusion reaction with the first cycle of liposomal doxorubicin. Neutropenia was the most common toxicity; in only 1 case was it grade 3, and no cases of grade 4 were seen. Doxorubicin plasma concentrations were best fit by a linear, two-compartment model. Liposomal doxorubicin plasma concentrations were best fit by a linear, one-compartment model. Treatment with liposomal doxorubicin was well tolerated overall. While monotherapy with liposomal doxorubicin has only modest activity in the treatment of HRPC, it may be of interest to study this agent as part of combination chemotherapy.