Phase I study of Caelyx (doxorubicin HCL, pegylated liposomal) in recurrent or metastatic head and neck cancer
Phase I study of Caelyx (doxorubicin HCL, pegylated liposomal) in recurrent or metastatic head and neck cancer
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DOI：
10.1023/a:1008319618638
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发表时间：
2000-03-01
影响因子：
50.5
通讯作者：
Comella, G
中科院分区：
文献类型：
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作者：
Caponigro, F;Comella, P;Comella, G
工作背景：聚乙二醇化脂质体技术代表了一种有利的药物载体系统，因为隐形脂质体药物具有降低的清除率和延长的循环半衰期以及在具有增加的血管通透性的组织（例如肿瘤组织）中的选择性药物蓄积。Caelyx是一种含有多柔比星的聚乙二醇化脂质体，已开发用于靶向癌细胞的药物递送，从而降低毒性。生物分布研究表明，晚期头颈癌（HNC）患者的选择性肿瘤摄取，从而证明了本I期研究的合理性。患者和方法：复发性或转移性HNC患者接受Caelyx治疗，起始剂量为30 mg/m2，每三周一次，逐步增加5 mg/m2。如果给定群组中超过三分之一的患者具有剂量限制性毒性（DLT），则停止剂量递增，所述剂量限制性毒性定义为4级中性粒细胞减少症或血小板减少症、3级发热性中性粒细胞减少症、3级血小板减少症伴出血、3级非血液学毒性（除了恶心和脱发）或化疗再循环延迟> 2周。上述剂量水平定义为最大耐受剂量（MTD），建议II期评价采用紧接其下的剂量水平。三个疗程的化疗后评价反应。结果：24例患者接受了五个剂量水平的治疗。在50 mg/m2时，6例患者中有3例发生3级口腔炎;因此，该水平定义为MTD，45 mg/m2是II期研究的选定剂量。考虑到所有给药周期，所有剂量水平的11例患者发生口腔炎。24例患者中有10例发生中性粒细胞减少，但在第4个剂量水平仅2例患者达到4级。皮肤毒性，主要表现为掌跖红斑，是最常见的毒性，发生在14例患者中。其他副作用轻微。观察到1例完全缓解（4%）和7例部分缓解（29%），总体缓解率为33%（95%置信区间（95%CI）：16%-55%）。结论：Caelyx是一种安全且有前途的HNC新治疗方法，值得进一步评估单独使用和与放化疗策略整合。
Background: Pegylated liposome technology represents a favourable drug-carrier system, since stealth liposomal drugs have a reduced clearance with prolonged circulation half-life and selective drug accumulation in tissues with increased vascular permeability, such as tumor tissues. Caelyx is a pegylated liposome containing doxorubicin, which has been developed to target drug delivery to cancer cells, thus reducing toxicities. Biodistribution studies have shown a selective tumor uptake in patients with advanced head and neck cancer (HNC), thus justifying the present phase I study.Patients and methods: Patients with recurrent or metastatic HNC were treated with Caelyx administered at the starting dose of 30 mg/m(2) every three weeks and escalated by 5 mg/m(2) per step. Dose escalation was stopped if more than a third of patients of a given cohort had dose-limiting toxicity (DLT), which was defined as grade 4 neutropenia or thrombocytopenia, grade 3 febrile neutropenia, grade 3 thrombocytopenia with bleeding, grade 3 non-hematologic toxicity (except for nausea and alopecia), or > 2 week delay in chemotherapy recycling. The above dose level was defined as maximum tolerated dose (MTD) and the dose level immediately below was recommended for phase II evaluation. Response was evaluated after three courses of chemotherapy.Results: Twenty-four patients were treated at five dose levels. At 50 mg/m(2), three out of six patients had grade 3 stomatitis; therefore, this level was defined as MTD and 45 mg/m(2) was the selected dose for phase II. Stomatitis occurred in 11 patients across all dose levels, considering all delivered cycles. Neutropenia occurred in 10 of 24 patients, but reached grade 4 in only 2 patients at fourth dose level. Skin toxicity, mainly appearing in the form of palmar-plantar erythrodysestesia, was the most frequent toxicity, occurring in 14 patients. Other side effects were mild. One complete response (4%) and seven partial responses (29%) were observed, for an overall response rate of 33% (95% confidence interval (95% CI): 16%-55%).Conclusions: Caelyx is a safe and promising new treatment in HNC, that deserves further evaluation both alone and integrated within chemo-radiotherapy strategies.