Vincristine efficacy and safety in treating immune thrombocytopenia: a retrospective study of 35 patients

Although vincristine (VCR) is sometimes prescribed for newly diagnosed immune thrombocytopenia (ITP), its efficacy in refractory ITP and sustained efficacy has yet to be demonstrated. We describe our clinical experience and recommend vincristine's correct place in ITP management. This retrospective study analysed data from 35 patients with newly diagnosed (ND), persistent (P) or chronic (C) ITP treated with VCR. The initial response rate, defined as >30 × 10⁹ platelets/L, reached 86% after a median of 7 [interquartile range (IQR) 6–13] days. In ND and P ITP, even when previous therapies were inefficient, initial response was 87.5%, suggesting that this treatment could be used particularly in rescue. Median survival time, without failure or relapse, was 15 months (Kaplan–Meier curve). Predictive factors (univariate analysis) of an initial and long‐term response were a small number of prior treatments received. However, at 2 yr, only seven patients had sustained response. Eight (23%) patients experienced adverse events: neuropathy for seven and bowel obstruction for one. Vincristine efficacy in ITP was confirmed, and it could be a good strategy for treating resistant ITP, especially in emergencies. In this era of new therapeutics, VCR deserves to remain on the list of ITP treatments because of its initial efficacy, safety and low cost.     

长春新碱误行鞘内注射致严重神经损害及预防

长春新碱为抗肿瘤药,仅用于静脉注射,误行鞘内注射可致严重神经损害,并常造成死亡。1968年Schochet等人首先报道了1例长春新碱误行鞘内注射引致死亡的病例。迄今至少有20例长春新碱误行鞘内注射引起死亡的病例,分布在美国、加拿大、英国、法国,沙特阿拉伯、新加坡、韩国和中国。据已发表的病例报告,长春新碱鞘内注射后患者迅速发生感觉和运动功能障碍,随后出现脑病、昏迷和死亡。早期体征和症状为震颤、定向力障碍,恶心和呕吐。患者在1周后出现反应迟钝。一些患者出现上行性麻痹。死亡时间为7～83d。患者在长春新碱误行鞘内注射后,应立即作如下处理:进行脑脊液置换,用乳酸钠林格注射液和乳酸钠林格注射液稀释的新鲜冷冻血浆灌洗,给予谷氨酸、叶酸、维生素B6等。长春新碱误行鞘内注射可能由单一用药错误或一系列用药错误所致。预防长春新碱误行鞘内注射发生的建议包括长春新碱注射器或外包装的标签应有警示语"仅用于静脉注射,鞘内注射可致死",用小输液袋代替注射器进行配制和静脉输注,长春新碱应与鞘内用药分开贮存和配发,由经专门培训和指定的肿瘤科专业人员配制和给药。     

长春新碱载药红细胞制备及其生物学特性研究

目的:探讨红细胞作为长春新碱(vincristine, VCR)载体的可行性及其载药参数和生物学特性,为其应用提供实验依据.方法:改良低渗预膨胀法制备VCR载体红细胞,高效液相色谱法分析载体红细胞内、外液VCR含量,自动血液分析仪测定红细胞生理指标,考察红细胞VCR载药量、载药率和载体细胞回收率等参数.采用4℃保存定时提取上清液比较VCR含量并观测上清液溶血情况、渗透脆性检测,以显微镜观察等方法考察载体红细胞的载药释放、贮存稳定、渗透脆性和形态等生物学特性.结果:预膨胀红细胞与VCR的0.6%盐水溶液作用后,单位数量(1×109/ml)红细胞载药量最高,达49.59 μg;预膨胀红细胞与上述VCR溶液作用20 min后载药达到稳定;VCR浓度在50～2 000 μg/ml范围内时,单位数量红细胞的载药量(y, μg)可按y=0.098 2 x-2.465 8计算,线性相关系数r =0.996 1.红细胞总载药率为(61.42±3.69)%,载体红细胞回收率为(90.61±4.95)%.载体红细胞渗透脆性减低,形态无明显变化,体积略有增大与载药量成正比(r =0.988 0),药物释放缓慢,4 h连续释放率(11.35±1.65)%,可稳定贮存5 d.结论:红细胞可作为VCR载药,载药参数良好,生物学特性无明显改变.     

Pharmacodynamic and pharmacokinetic study of pegylated liposomal doxorubicin combination (CCOP) chemotherapy in patients with peripheral T-cell lymphomas

Aim:

To investigate the pharmacodynamic and pharmacokinetic parameters of pegylated liposomal doxorubicin (PLD) combined with cyclophosphamide, vincristine, and prednisolone in patients with peripheral T-cell lymphomas (PTCL).

Methods:

Seven chemonaive patients and four patients with relapsed peripheral T-cell lymphomas were treated with a CCOP regimen consisting of an intravenous administration of cyclophosphamide (750 mg/m²), vincristine (1.4 mg/m²), and PLD (30 mg/m²) on d 1, as well as an oral administration of prednisolone (60 mg/m²) on d 1–5. This regimen was repeated every 3 weeks for six cycles, and the clinical response and toxicity of the regimen were monitored. In addition, the plasma concentration of PLD at different time points was determined before and after treatment. The pharmacokinetics (PKs) software was used to estimate the pharmacokinetic parameters of PLD.

Results:

The 11 PTCL patients received 35 treatment cycles. Three of them achieved complete response (CR), two partial response (PR), four stable disease (SD), and two progressive disease (PD). The overall response rate (ORR) was 45.5%, and the CR rate was 27.3%. In the 7 chemonaive patients, three achieved CR, two PR, one SD, and one PD. The ORR was 71.4%, and CR rate was 42.9%. The median follow-up time was 15 months, but 6 out of 11 patients were dead at the time of data analysis. The 1-year overall survival rate was 45.5%, and the median progression-free survival (PFS) rate was 6.5 [95% confidence interval (95% CI) 3.17–19.02] with a survival rate of 11.5 months (95% CI 6.65–16.36). The main toxicity was myelosuppression. Oral mucositis and hand-foot syndrome seldom occurred. The PLD plasma concentration from nine patients ranged from 1.7036 to 9.2207 mg·L⁻¹ after administration of the CCOP regimen (0–168 h). The pharmacokinetic parameters AUC_0–∞, CL, t_1/2, and V_d were 910.76 mg/L·h, 0.043 L·h⁻¹·m⁻², 68.40 h, and 3.56 L/m², respectively.

Conclusion:

The CCOP regimen was effective and well tolerated in patients with peripheral T-cell lymphomas. The results of the pharmacokinetic parameters showed that PLD had long retention time in blood circulation.     

Evaluation of pre-existing neuropathy and bortezomib retreatment as risk factors to develop severe neuropathy in a mouse model

Pre-existing neuropathy, a not uncommon feature in oncologic patients, is a potential but non-confirmed risk factor to develop early or severe chemotherapy-induced neuropathy. The main goal of this study is to evaluate the role of pre-existing neuropathy induced by vincristine (VNC) or bortezomib (BTZ) as a risk factor to develop more severe BTZ-induced neuropathy in a mouse model. VNC, at doses of 1 and 1.5 mg/kg given twice per week for 4 weeks, induced a moderate and severe sensory-motor neuropathy, primarily axonal, with predominant involvement of myelinated sensory axons. The neuropathy induced by BTZ at dose of 1 mg/kg given twice per week for 6 weeks was a mild axonal sensory neuropathy involving myelinated and unmyelinated fibers. The neuropathy in mice previously treated and retreated with the same schedule of BTZ after 4 weeks of washout period was similar in profile and severity to the one observed after the first treatment. When basal neuropathy was classified as moderate (most of BTZ-treated animals) or severe (all VNC-treated animals and two BTZ-treated animals), there was a more marked decline in sensory nerve function during BTZ retreatment in the group with basal severe neuropathy (-86%) than in the groups with basal mild (-57%) or without neuropathy (-52%; p < 0.001). Histopathological findings supported the functional results. Therefore, this study shows that the presence of a severe neuropathy previous to treatment with an antitumoral agent, such as BTZ, results in a more marked involvement of peripheral nerves.     

两种硫酸长春新碱脂质体包封率测定方法的比较

目的:建立两种测定硫酸长春新碱脂质体包封率的方法,并对测定结果进行比较.方法:分别以葡聚糖凝胶Sephadex G-50柱和阳离子交换树脂柱分离硫酸长春新碱脂质体和游离药物,采用HPLC法测定药物含量,计算包封率,并用SPSS软件进行t检验.结果:两种方法测定不同药脂比的硫酸长春新碱脂质体包封率,测定结果无显著性差异.结论:葡聚糖凝胶柱法的建立需详细考察凝胶的种类对分离度的影响;阳离子交换树脂法分离度良好,分离速度快,为优选的方法.     

Complete response to multidisciplinary therapy in a patient with primary gastric choriocarcinoma

Primary gastric choriocarcinoma is a rapidly growing neoplasm with an average survival of several months in untreated patients.Gastrectomy with lymph node dissection followed by chemotherapy is the treatment of choice.Regimens used for gastric adenocarcinoma are usually selected.However,median survival remains less than six months.In this case report,we describe a case of primary gastric choriocarcinoma with a clinical complete response to multidisciplinary treatment including surgery,chemotherapy,and radiofrequency ablation(RFA).The patient was originally referred for general malaise.Esophagogastroduodenoscopy demonstrated a large tumor occupying the fornix,and total gastrectomy with lymph node dissection was performed.Seven days later,multiple liver metastatic recurrences with high serum levels of beta-human chorionic gonadotropin(β-hCG) were recognized.Chemotherapy with a gonadal choriocarcinoma regimen consisting of etoposide,methotrexate,actinomycin D,cyclophosphamide,and vincristine(EMA/CO),was initiated.After three cycles,serum β-hCG decreased markedly and the tumors disappeared.Six months later,multiple lung metastatic recurrences were found.After one cycle of EMA/CO,only one nodule remained.Computed tomography-guided RFA was performed for this oligometastatic tumor.The patient has been alive with no evidence of disease for 10 years after the initial diagnosis.To the best of our knowledge,this patient with recurrent primary gastric choriocarcinoma has achieved the longest survival.The present case is the first report of choriocarcinoma metastatic to the lung successfully treated with RFA.From our retrospective analysis of recurrent or unresectable primary gastric choriocarcinoma,we propose that gonadal choriocarcinoma regimens can be considered as first-line for primary gastric choriocarcinoma.     

Cyclophosphamide plus Vincristine and Prednisone in the Treatment of Severe Pemphigus Vulgaris Refractory to Conventional Therapy

Five patients with severe pemphigus vulgaris refractory to conventional therapy with azathioprine and corticosteroids were treated with cyclophosphamide, vincristine and prednisone. One patient was not evaluable, while the remaining four patients showed a complete response. Duration of response was in the range of 13-94 months. Toxicity was mainly represented by alopecia, myelosuppression and gastrointestinal side-effects such as nausea/vomiting. Although cyclophosphamide and vincristine may induce severe side-effects, this association may be useful in controlling severe disease resistant to previous conventional therapies.