紫杉醇和卡铂联合抗血管生成靶向药物治疗转移性黏膜型恶性黑素瘤的临床研究

Paclitaxel and carboplatin combined with antiangiogenesis therapy for patients with metastatic mucosal malignant melanoma

目的 ：观察紫杉醇和卡铂联合抗血管生成靶向药物治疗转移性黏膜型恶性黑素瘤患者的疗效和安全性。方法：经病理组织学确诊的46例转移性黏膜型恶性黑素瘤患者接受紫杉醇和卡铂联合抗血管生成靶向药物治疗：紫杉醇175 mg/m2静脉滴注d 1,卡铂静脉滴注的药时曲线下面积（area under the curve,AUC）=5 mL/min d 1,重组人血管内皮抑素15 mg/d静脉滴注d 1~14或贝伐珠单抗5 mg/kg静脉滴注d 1和d 15;每4周为1个化疗周期,直至肿瘤进展患者或不能耐受化疗的不良反应。每个化疗周期结束后评价近期疗效,观察不良反应。对所有患者进行随访,计算无进展生存（progression-free survival,PFS）时间和总生存（overall survival,OS）时间。结果：46例患者均可评价疗效,分别接受1~6个周期的化疗,平均为（3.7±1.1）个周期。46例患者中,完全缓解1例,部分缓解3例,疾病稳定23例,疾病进展19例;客观有效率为8.7%（4/46）,临床获益率为58.7%（27/46）;中位PFS时间为3.0个月（95%可信区间：1.7~4.3个月）,中位OS时间为10.0个月（95%可信区间：7.3~12.7个月）。多因素分析结果显示,血清乳酸脱氢酶水平升高组患者的OS优于正常组患者,血清乳酸脱氢酶水平是OS的独立预后因素[风险比为0.436（95%可信区间：0.193~0.985）;P=0.046]。最常见的严重不良反应（3/4级）主要为骨髓抑制,包括白细胞减少（12例,26.1%）和血小板减少（2例,4.3%）;3/4级外周神经毒性发生率为10.9%（5/46）。结论：转移性黏膜型恶性黑素瘤患者接受紫杉醇和卡铂联合抗血管生成靶向药物治疗可有临床获益,且耐受性良好。该治疗方案的具体可行性仍有待今后开展更多的临床试验予以验证。

Objective： To observe the efficacy and safety of paclitaxel and carboplatinc ombined with antiangiogenesis therapy in patients with metastatic mucosal melanoma.Methods： Paclitaxel（175 mg/m2 d1） and carboplatin [area under the curve（AUC） = 5 mL/min d1] combined with recombinant human endostar（15 mg/d d1-14o） r bevacizumab（5 mg/kg d1, d15） were administrated to 46 patients withm etastatic mucosal melanoma,which had been conf rmed by histopathology. The regimen was repeated every 28 days and would continue until the patients achieved progression or had untolerated side effects. The response and toxicity were evaluated after the end of each cycle. All patients were followedup.The progression-free survival（PFS） and overall survival（OS） were analyzed.Results： The number of cycles given was 1-6（mean： 3.7±1.1）. Among4 6 evaluable cases, one case achieved complete response, three achieved partial response, 23 a chieved stable disease, and tumor progression was seen in 19 cases. The objective response rate was 8.7%（4/46） and the clinical bene fit rate was 58.7%（27/46）. The median PFS reached 3.0 months [95% conf dence interval（CI）： 1.7-4.3]and the median OS reached 10.0 months（95% CI ： 7.3-12.7）. Mutivariate analysis revealed that, as compared with the patients with normal serum lactate dehydrogenase（L DH） level, the patients with elevated serum LDH level had a better OS [hazard ratio： 0.436（95% CI ： 0.193-0.985）; P = 0.046].The main grade 3/4 toxicity was myelosuppression, includingn eutropenia（ n = 12, 26.1%） and thrombocytopenia（n = 2, 4.3%）; the rate of grade 3/4 peripheral neuropathy was 10.9%（5/46）.Conclusion： Paclitaxel and carboplatin combined with antiangiogenesis therapy for patients with metastatic mucosal melanoma can achieve clinical benifit and it is well tolerated. More clinical trials should be needed to comf rm the efficacy of this regimen.