Objective: To compare the bioequiavailability of paclitaxel for injection (albumin bound) (PAB) and reference listed drug abraxane in the patients with metastatic breast cancer, and to investigate the safety and efficacy in the extension treatments of PAB. Methods: This study was random, two cycles, self-crossover control study in the bioequiavailability stage. PAB was the investigational drug T and Abraxane was the reference drug R. Patients were randomly assigned to two cycles therapy of either R→T or T→R(260 mg/m(2)/21d). Non-PD patients entered in the extension treatments of the investigational drug PAB(260 mg/m(2)/21d) until the disease progression or the intolerance toxicity. Results: From Mar 1, 2016 to May 24, 2016, we enrolled 40 patients. The blood concentration-time curve and the parameters of pharmacokinetics indicated the two drugs were the bioequivalent drug products in the initial two cycles crossover-therapy.The incidence of adverse drug reactions were 89.7% vs 97.4% in investigational drug vs reference drug and grade 3/4 toxicities were 20.5% vs 21.1%(P=1.000). Patients received a median of 7 treatment cycles(range 1-23) and a median of 260mg/m(2) actual drug dose (range 220-260 mg/m(2)). Seven patients (17.5%) had dose reductions because of toxicities (260 mg/m(2) reduce to 220 mg/m(2)). Twenty-two patients (55%) discontinued treatment prematurely because of toxicity.Overall response rates (ORR) were 40% (95% CI, 24.8%-55.2%). For patients who received PAB as first-line vs non-first-line therapy, the ORR were 43.8% vs 25%. For patients who taxane-naïve vs taxane-pretreated, the ORR were 45.5% vs 37.9%. Median PFS was 49 weeks(95% CI, 30weeks-NA). Conclusion: The paclitaxel for injection (albumin bound) (PAB) and reference listed drug abraxane are the bioequivalent drug products.The toxicity and efficacy of the PAB are similar with abraxane.The more therapy chances for Chinese patients will come by the research and development of domestic drugs.
目的： 比较注射用紫杉醇(白蛋白结合型)(PAB)(克艾力)与原研药Abraxane用于转移性乳腺癌的生物等效性，探索PAB延长用药的安全性和疗效。 方法： 利用生物等效性研究采用随机、两周期、自身交叉对照研究设计(PAB为试验药T，Abraxane为参比药R)，受试者随机接受R→T或T→R 2周期治疗(260 mg/m(2)共21 d)；非PD受试者进入延长用药期，均应用试验药(260 mg/m(2)共21 d)直至疾病进展或毒性不可耐受。 结果： 2016年3月1日至5月24日，共纳入40例转移性乳腺癌患者。初始两周期交叉用药的血药浓度—时间曲线和药代动力学参数表明两种制剂为生物等效制剂。试验药与参比药不良反应发生率分别为89.7%、97.4%，其中3/4级不良反应发生率为20.5%、21.1%，两组间差异无统计学意义(P＝1.000)。中位用药周期数7(1～23)，中位实际用药剂量260 mg/m(2)(220～260 mg/m(2))，因毒性反应减低剂量7例(17.5%)，均由260 mg/m(2)降低为220 mg/m(2)，因毒性反应结束用药22例(55%)。ORR为40%(95% CI, 24.8%～55.2%)，解救一线治疗有效率高于非一线治疗(43.8%与25%)，既往未接受过紫杉类治疗的患者较接受过患者有效率高(45.5%与37.9%)。中位PFS为49周(95% CI, 30周～NA)。 结论： 注射用紫杉醇(白蛋白结合型)(克艾力)与原研药Abraxane是生物等效制剂，其毒性反应及疗效亦与原研药无显著差异，国产药物的研发为中国患者创造了更多的治疗机会。.
Keywords: Bioequiavailability; Efficacy; Metastatic breast cancer; Paclitaxel for injection(Albumin Bound); Safety.