Phase II study of perifosine in previously untreated patients with metastatic melanoma
Phase II study of perifosine in previously untreated patients with metastatic melanoma
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DOI：
10.1007/s10637-005-1157-4
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发表时间：
2005-12-01
影响因子：
3.4
通讯作者：
Smylie, M
中科院分区：
文献类型：
--
作者：
Ernst, DS;Eisenhauer, E;Smylie, M
目的：评估的alkylphosphocholine类似物，perifosine，在转移性或复发性恶性melanoma.Patients和方法的患者的反应率和毒性：患者有组织学证明，unidimensionally可测量的疾病，这是无法治愈的标准治疗。允许既往辅助免疫治疗，但患者既往未接受过化疗。在28天的周期中，在第1天口服900 mg负荷剂量的培立福新，然后在第2-21天口服150 mg维持剂量。所有后续周期的第1天负荷剂量为300 mg。结果：18例患者在7个月以上获得肿瘤缓解。14例可评价患者中未出现客观缓解。3例患者（21%）在2个周期后达到疾病稳定，11例出现进展。17例患者可评价毒性。3级或4级非血液学毒性包括：腹泻（12%）、关节痛（12%）、恶心（6%）、头痛（6%）和疲乏（6%）。未观察到3级或4级血液学或生化毒性。77%的患者接受了>= 90%的计划周期1剂量强度，58%的患者接受了>= 90%的计划周期2+剂量。4例患者需要减少剂量;治疗延迟5例;和5例错过剂量，因为toxicity.Conclusions：哌立福新可以安全地给予时，作为初始负荷剂量，然后每天维持治疗超过28天。胃肠道毒性很常见，但通常是低度的。血液学毒性极小。没有观察到客观反应。不建议在恶性黑色素瘤中进一步开发单药哌立福新。
Purpose: To assess the response rate and toxicity of the alkylphosphocholine analogue, perifosine, in patients with metastatic or recurrent malignant melanoma.Patients and Methods: Patients had histologically proven, unidimensionally measurable disease which was incurable by standard therapy. Prior adjuvant immunotherapy was allowed but patients had not received prior chemotherapy. Perisfosine was given orally as a loading dose of 900 mg on day I followed by a maintenance dose of 150 mg po on days 2-21 in a 28 day cycle. The loading dose was 300 mg on day 1 of all subsequent cycles. Tumour response was assessed every 2 cycles.Results: 18 patients were accrued over 7 mos. No objective responses occurred in the 14 evaluable patients. Three patients (21%) achieved stable disease after 2 cycles and 11 had progression. Seventeen patients were evaluable for toxicity. Grade 3 or 4 non-hematologic toxicities included: diarrhea (12%), arthralgia (12%), nausea (6%), headache (6%), and fatigue (6%). No grade 3 or 4 hematological or biochemical toxicity were observed. Seventy-seven percent of patients received >= 90% of planned cycle 1 dose intensity and 58% received >= 90% of planned dose for cycle 2+. Four patients required dose reductions; treatment was delayed in 5 patients; and 5 patients missed doses because of toxicity.Conclusions: Perifosine can be safely administered when given as an initial loading dose followed by daily maintenance therapy over 28 days. Gastrointestinal toxicity is common but generally of low grade. Hematological toxicity is minimal. No objective responses were observed. No further development of single-agent perifosine is recommended in malignant melanoma.