Effects of vinorelbine combined with adriamycin on breast cancer MCF-7 cells and related mechanisms / 中华内分泌外科杂志

Objective:To investigate the in vitro anti-cancer effect of Vinorelbine (NVB) combined with adriamycin (PLD) on human breast cancer MCF-7 cells and related mechanisms.Methods:The effects of NVB and PLD alone or in combination on the proliferation of breast cancer cells were detected by CCK-8 experiment. Flow cytometry was used to detect cell apoptosis and changes in reactive oxygen species (ROS) levels. Western blot experiment was carried out to detect protein expression.Results:The results of CCK-8 showed that compared with the blank control group, the inhibition rates of the vinorelbine treatment group, the adriamycin treatment group and the combined treatment group were 27.6%, 31.2% and 65.4%, compared with the NVB group and PLD group, the difference between the combined treatment group was statistically significant ( P=0.005 vs 0.001) . The results of flow cytometry showed that the proportion of apoptotic cells in each group was 3.54%, 16.95%, 15.01% and 32.24%, compared with the NVB group and PLD group, the difference between the combined treatment group was statistically significant ( P=0.006 vs 0.005) . The levels of reactive oxygen species in each group were 1, 1.03, 1.06 and 1.57, compared with the NVB group and PLD group, the difference between the combined treatment group was statistically significant ( P=0.008 vs 0.007) . Western blot results showed that the expression of p-ERK and p-STAT3 decreased after the combination of NVB and PLD, which inhibited the ERK/STAT3 signaling pathway. Conclusions:The combination of NVB and PLD can promote the apoptosis of breast cancer cells and inhibit the proliferation of breast cancer cells with high efficiency and low toxicity. Its mechanism of action may be related to the up-regulation of ROS levels in cells, thereby inhibiting the activation of the ERK/STAT3 pathway.

Research progress on pharmacokinetics and toxicity of vinorelbine / 中国药房

Vinorelbine（NVB）is a semisynthetic vinca alkaloid and can play an anti-tumor role by inhibiting the synthesis of tubulin. Its oral preparation has been used in the treatment of a variety of tumors as its convenience and good clinical response. The blood concentration of NVB is closely related to its curative effect and toxicity. Small variations in blood concentration may reduce the curative effect and even produce serious toxicity. There are some risks in the clinical drug use due to limited clinical data and effective pharmacodynamic monitoring methods. By reviewing the relevant literature at home and abroad ，this paper summarizes the research progress of in vivo pharmacokinetics and toxicity of NVB ，fully understands the pharmacokinetic characteristics and influencing factors of NVB ，the influencing factors of toxicity ，and the application status of pharmacokinetics in the adjustment of administration scheme ，so as to provide reference for its clinical rational use.

Reevaluation of systematic evaluation of gemcitabine combined with cisplatin in the treatment of advanced non- small cell lung cancer / 中国药房

OBJECTIVE To reevaluate the system atic evaluation of g emcitabine combined with cisplatin in the treatment of advanced non-small cell lung cancer （NSCLC），in order to provide evidence-based evidence for the treatment of NSCLC. METHODS Retrieved from Wanfang database ，CNKI，VIP，PubMed，Embase，systematic evaluation of gemcitabine combined with cisplatin versus pemetrexed/vinorelbine combined with cisplatin in the treatment of advanced NSCLC was included from the inception to Dec. 2021. RevMan 5.3 system evaluation software was used for meta-analysis of various outcome indicators ； AMSTAR2 scale was used for methodological quality evaluation ，and GRADE tool was used for evidence quality evaluation. RESULTS A total of 9 literatures were included. Meta-analysis showed that the effective rate of gemcitabine combined with cisplatin was significantly lower than pemetrexed combined with cisplatin ，but was similar to vinorelbine combined with cisplatin. The 1-year survival rate of gemcitabine combined with cisplatin was equivalent to that of pemetrexed combined with cisplatin ，but was superior to vinorelbine combined with cisplatin. There was no significant difference in the incidence of nausea and vomiting between gemcitabine combined with cisplatin and pemetrexed/vinorelbine combined with cisplatin. Gemcitabine combined with cisplatin had a higher incidence of thrombocytopenia than pemetrexed/vinorelbine combined with cisplatin. The incidence of neutropenia and leukopenia in gemcitabine combined with cisplatin were higher than pemetrexed combined with cisplatin ，but were significantly lower than vinorelbine combined with cisplatin. The evaluation results of AMSTAR 2 scale showed that 6 systematic evaluation were of low quality in methodology and 3 were of very low quality. The results of the GRADE tool showed that 31％ of the outcome indicators were of medium quality （14 items），27％ were of low quality （12 items），and 42％ were of very low quality（19 items）. Research limitations and publication bias were the most frequently downgraded factors. CONCLUSIONS Gemcitabine combined with cisplatin has advantages over 154854280@qq.com vinorelbine combined with cisplatin in the efficacy and safety of ad vanced NSCLC ，especially in the 1-year survival rate ，the incidence of neutropenia and leucopenia. The efficacy and safety of gemcitabine combined with cisplatin are inferior to those of pemetrexed combined with cisplatin. However ，the methodological quality and evidence level of systematic evaluation are not high on the whole ，and the overall quality of research needs to be improved.

Effectiveness and toxicity of adjuvant chemotherapy in patients with non-small cell lung cancer / Eficácia e toxicidade da quimioterapia adjuvante em pacientes com câncer de pulmão de células não pequenas

ABSTRACT Objective: Adjuvant chemotherapy (AC) improves survival of patients with resected non-small cell lung cancer (NSCLC). However, the cisplatin-vinorelbine regimen has been associated with a significant risk of clinically relevant toxicity. We sought to evaluate the effectiveness, safety, and feasibility of AC for NSCLC patients in a real-world setting. Methods: This was a single-center, retrospective cohort study of patients with stage I-III NSCLC undergoing surgery with curative intent between 2009 and 2018. AC was administered at the discretion of physicians. The patients were divided into two groups: AC group and no AC (control) group. Study outcomes included overall survival (OS) and recurrence-free survival (RFS), as well as the safety profile and feasibility of the cisplatin-vinorelbine regimen in a real-world setting. Results: The study involved 231 patients, 80 of whom received AC. Of those, 55 patients received the cisplatin-vinorelbine regimen. Survival analyses stratified by tumor stage showed that patients with stage II NSCLC in the AC group had better RFS (p = 0.036) and OS (p = 0.017) than did those in the no AC group. Among patients with stage III NSCLC in the AC group, RFS was better (p < 0.001) and there was a trend toward improved OS (p = 0.060) in comparison with controls. Of those who received the cisplatin-vinorelbine regimen, 29% had grade 3-4 febrile neutropenia, and 9% died of toxicity. Conclusions: These results support the benefit of AC for NSCLC patients in a real-world setting. However, because the cisplatin-vinorelbine regimen was associated with alarming rates of toxicity, more effective and less toxic alternatives should be investigated.

RESUMO Objetivo: A quimioterapia adjuvante melhora a sobrevida de pacientes com câncer pulmonar de células não pequenas (CPCNP) ressecado. No entanto, o esquema cisplatina-vinorelbina está relacionado com risco significativo de toxicidade clinicamente relevante. Nosso objetivo foi avaliar a eficácia, segurança e viabilidade da quimioterapia adjuvante para pacientes com CPCNP em um cenário de mundo real. Métodos: Estudo retrospectivo de coorte realizado em um único centro com pacientes com CPCNP em estágio I-III submetidos a cirurgia com intuito curativo entre 2009 e 2018. A quimioterapia adjuvante foi administrada a critério dos médicos. Os pacientes foram divididos em dois grupos: quimioterapia adjuvante e sem quimioterapia adjuvante (grupo controle). Os desfechos estudados foram sobrevida global (SG) e sobrevida livre de recidiva (SLR), bem como o perfil de segurança e viabilidade do esquema cisplatina-vinorelbina em um cenário de mundo real. Resultados: O estudo envolveu 231 pacientes, 80 dos quais receberam quimioterapia adjuvante. Destes, 55 receberam o esquema cisplatina-vinorelbina. As análises de sobrevida estratificadas pelo estágio do tumor mostraram que os pacientes com CPCNP em estágio II que receberam quimioterapia adjuvante apresentaram melhor SLR (p = 0,036) e SG (p = 0,017) do que os do grupo controle. Entre os pacientes com CPCNP em estágio III que receberam quimioterapia adjuvante, a SLR foi melhor (p < 0,001) e houve uma tendência a melhor SG do que no grupo controle (p = 0,060). Dos que receberam o esquema cisplatina-vinorelbina, 29% apresentaram neutropenia febril de grau 3-4, e 9% morreram em virtude de toxicidade. Conclusões: Os resultados confirmam o efeito benéfico da quimioterapia adjuvante em pacientes com CPCNP em um contexto real. No entanto, o esquema cisplatina-vinorelbina relacionou-se com taxas alarmantes de toxicidade e alternativas mais eficazes e menos tóxicas devem ser investigadas.

A randomized controlled Phase II trial of vinorelbine plus capecitabine versus docetaxel plus capecitabine in anthracycline-pretreated women with metastatic breast cancer

Background: Previous studies have shown that vinorelbine/capecitabine (NX) and docetaxel/capecitabine (TX) chemotherapy has a certain effect in advanced breast cancer. However, there are few clinical studies directly comparing TX and NX regimen chemotherapy, especially in patients with advanced breast cancer previously treated with anthracycline and taxane. The purpose of this Phase II study was to compare survival and side effects between patients with anthracycline- and taxane-resistant advanced breast cancer treated with NX and those treated with TX chemotherapy. Patients and Methods: From February 2012 to March 2014, a total number of 97 patients were randomly assigned to NX (n = 55) or TX (n = 42). Baseline characteristics were relatively well-balanced in the two treatment arms. The clinical trial registration number (clincaltrials.gov) is NCT01635465. Results: After a median follow-up of 46.0 months, there was no significant difference between the NX and TX arms in objective response rate (17.9% vs. 21.1%; P = 0.686) and progression-free survival (6 months vs. 7 months; P = 0.560). The overall survival period of the TX arm was longer than that of the NX arm (32 months vs. 27 months) but without statistical significance. Both regimens were well-tolerated. The main toxicities were neutropenia, leukopenia, and anemia. In the TX arm, hand-foot syndrome occurred more frequently than in the NX arm (P < 0.01), but frequencies of other minor adverse effects were similar between the two arms. Conclusion: NX and TX regimens are both alternative treatments for patients with anthracycline- and taxane-resistant advanced breast cancer, but the safety profile was more favorable and manageable with the NX regimen. Trial Registrations: ClinicalTrials.gov NCT01635465. Registered 09 July 2012

Effect and mechanism of aspirin combined with vinorelbine on non-small cell lung cancer / 中国中药杂志

The study aimed to investigate the effect and mechanism of aspirin combined with vinorelbine on the proliferation and apoptosis of non-small cell lung cancer cells. 3-(4-dimethylthiazolyl-2)-2-diphenyltetrazolium bromide(MTT) was used to detect the cytotoxic effect of aspirin and vinorelbine on H460 and A549 cells, and half of inhibitory concentration(IC_(50)) value of drugs as well as synergistic effect were calculated. The results showed that both aspirin and vinorelbine inhibited the cancer cells proliferation by a concentration-dependent manner with IC_(50 )values of 1.553 mmol·L~(-1) and 0.033 μmol·L~(-1) in H460 cells, respectively. The IC_(50 )values of aspirin and vinorelbine were 1.70 mmol·L~(-1)and more than 20 μmol·L~(-1) in A549 cells. The combination index(CI) value was used to evaluate the combined effect of two drugs. Aspirin combined with vinorelbine had synergistic effects at the ratio of 100∶1 on H460 cells and 1∶10 on A549 cells(CI<1). Clone formation and 4',6-diamidino-2-phenylindole(DAPI)/propidium iodide(PI) staining assays were used to verify the effect of the combination of two drugs on proliferation of H460 cells. Compared with the aspirin single group, the combination group had stronger inhibitory effect on the proliferation of H460 cells and the clone formation rate was 49.5%(P<0.05). Furthermore, apoptosis, mitochondrial membrane potential, reactive oxygen species and Western blot experiments were used to explore the synergistic mechanism of aspirin combined with vinorelbine in inhibiting cell proliferation. The results showed that the cancer cell apoptosis rate was 52.8%, the mitochondrial membrane potential was decreased to 33.1%, and the levels of reactive oxygen species was increased to 73.3% in combination group, which were significantly different from those of the single drug treatment groups(P<0.05). Western blot showed that combination group significantly up-regulated the expressions of Bax, p53, cleaved caspase-3 and cytochrome C, while down-regulated the expression of anti-apoptosis proteins such as Bcl-xL and Bcl-2 when compared with single groups. Our results suggested that aspirin combined with vinorelbine could synergistically inhibit the proliferation of H460 cells by inducing the cell apoptosis through the mitochondrial pathway.

Application of metronomic chemotherapy in the treatment of advanced non-small cell lung cancer / 国际肿瘤学杂志

Metronomic chemotherapy is a brand-new and multi-target chemotherapy strategy.Totally different from the traditional chemotherapy,metronomic chemotherapy can exert synergistic and durable anti-tumor effects via multiple mechanisms,including cytotoxic effect,anti-angiogenesis,immune regulation and so on.Single and combined therapy modes of metronomic oral vinorelbine have good curative effects and safeties for the treatment of advanced non-small cell lung cancer.With the in-depth understanding of metronomic chemotherapy,it will certainly become an important treatment mode for advanced non-small cell lung cancer.

Compare therapeutic effects and adverse effects between TEC-NX regime and TEC regime in adjuvant chemotherapy of local advanced breast cancer patients / 国际外科学杂志

Objective To compare the difference of efficacy and adverse effects between TEC-NX regimen (Docetaxel + Epirubicin + Cyclophosphamide sequential Vinorelbine + Capecitabine) with TEC regimen (Docetaxel + Epirubicin + Cyclophosphamide) in the adjuvant chemotherapy of locally advanced breast cancer.Methods A retrospective study was conducted to select 58 patients with locally advanced breast cancer who underwent ≥4 axillary lymph node metastasis from April 2008 to April 2015 at the International Peace Maternity and Child Health Hospital,Shanghai Jiao Tong University School of Medicine.All patients were female,average age was 48 years old,rang from 29 to 63 years old.Patients were divided into TEC-NX group (n =23) and TEC group (n =35) according to different treatment methods.TEC-NX group patients received chemotherapy with TEC-NX regimen and TEC group patients received chemotherapy with TEC regimen.The 3-year overall survival rate and 3-year disease-free survival rate were compared between the two groups.The differences in adverse reactions such as myelosuppression,liver dysfunction and fever were compared between the two groups.The Chi-square test was used to compare the count data between the two groups;the survival analysis was performed by Kaplan-Meier method.Results The 3-year overall survival rate was 91.3％ in the TEC-NX group and 91.4％ in the TEC group,and the difference was not statistically significant (P =0.995).The 3-year disease-free survival rate was 73.9％ in the TEC-NX group and 85.7％ in the TEC group,and the difference was not statistically significant (P=0.289).The incidence of grade Ⅲ or Ⅳ myelosuppression in the TEC-NX group was 26.0％,which was significantly lower than that in the TEC group (65.7％),and the difference was statistically significant (P =0.009).The incidence of liver dysfunction was 91.3％ in the TEC-NX group,and there was not statistically significant compared with 93.5％ in the TEC group (P =0.523).The incidence of fever in the TEC-NX group was 17.4％,which was not statistically significant compared with the TEC group (14.3％) (P =0.749).Conclusion In adjuvant chemotherapy for locally advanced breast cancer,the TEC-NX regimen does not improve 3-year overall survival and disease-free survival compared with the TEC regimen,but the TEC-NX regimen significantly reduced the incidence of grade Ⅲ or Ⅳ myelosuppression.

Vinorelbine induces apotosis and decreases telomerase activity in human epithelial ovarian cancer cells line SKOV 3 / 基础医学与临床

Objective To investigate the effect of different concentrations of vinorelbine on apoptosis ,telomerase ac-tivity and expression of human telomerase-reverse transcriptase gene ( hTERT ) in human epithelial ovarian cancer cells SKOV3.Methods Ovarian cancer cells SKOV 3 were treated with vinorelbine under different concentrations . The cell proliferation was measured by cell counting kit-8 ( CCK-8) assay , and the cell apoptosis was detected by flow cytometry.The telomerase activity of SKOV3 cells was determined by TRAP-PAGE-silver staining;The mRNA expression of hTERT was performed by RT-PCR assay .Results Vinorelbine could significantly inhibited the prolifer-ation of SKOV3 cells,induce cell apoptosis (P<0.01),reduce the telomerase activity and expression of hTERT mRNA (P<0.01), in dependent of a concentration-time manner.Conclusions The detection of telomerase activity and the mRNA expression of hTERT might be vital for predicting the prognosis of patients with epithelial ovarian cancer .

Optimization of Wheat Germ Agglutinin Modified Vinorelbine Cationic Liposomes Formulation and Cytotoxicity Test / 中国药房

OBJECTIVE: To prepare Wheat germ agglutinin (WGA) modified vinorelbine (VRB) cationic liposomes (WGA-VRB cationic liposomes), and to optimize the formulation and conduct cytotoxicity test.METHODS: Thin-film diffusion and ammonium sulfate gradient method were used to prepare WGA-VRB cationic liposomes using phospholipid and cholesterol as excipient, 3β-[N-(N' -N' -dimethyl aminoethane) -carbamoyl] cholesterol hydrochloride (DC-Chol) as cationic material, distearoyl phosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG2000) as long cycle chain. Using encapsulation rate as index, central composite design-response surface methodology was used to optimize the amount of DC-Chol, cholesterol and VRB. The contents of VRB in VRB liposomes and WGA-VRB cationic liposomes were determined. The effects of them and blank cationic liposomes on survival rates of human breast cancer cell MCF-7 and human non-small cell lung cancer cells A549 were compared. RESULTS: The optimal formulation of 5 mL WGA-VRB cationic liposomes was as follows as phospholipid 22 mg, cholesterol 12 mg, DC-Chol 8 mg, VRB 0. 5 mg. Encapsulation rate of the liposomes was (92. 24 ± 1. 21)％ (n=3), relative error of which to predicted value was 5. 3％. The contents of VRB in VRB liposomes and WGA-VRB cationic liposomes were (96. 01 ± 3. 26), (93. 39 ± 1. 59) μg/mL(n=3). Compared with blank cationic liposomes and VRB liposomes, WGA-VRB cationic liposomes could significantly reduce survival rate of MCF-7 and A549. CONCLUSIONS: WGA-VRB cationic liposomes are prepared successfully. Inhibitory effect of WGA-VRB cationic liposomes on MCF-7 and A549 cell survival is stronger than that of VRB liposomes.

Preparation of the vinorelbine nanoemulsion and factors influencing the stability / 国际药学研究杂志

Objective To investigate the intravenous lipid emulsion of vinorelbine, stability of the emulsion and factors influencing the stability. Methods The vinorelbine intravenous lipid emulsion injection was prepared by the processing process including the colostrum preparation, high pressure homogenization, filling and sealing, and rotary hot pressing sterilization. The effect of different temperatures on the stability of the emulsion was investigated by the orthogonal design using the emulsion particle size, pH and drug content as indicators. Results The three batches of pilot products were characterized by the emulsion particles with the average particle size ＜300 nm, uniform particle size distribution and no more than 1μm particles, as detected by the dynamic light scattering method. The emulsion showed an excellent stability at 5℃ within 6 months, but a gradual increase of the temperature significantly affected the stability of the emulsion, which caused the increase of particle size and decrease of pH. Conclusion The key parameters, processing conditions and engineering supports from the present study might be helpful for the industrial production of the drug-containing lipid nanoemulsion of vinorelbine for intravenous injection.

Preparation of Vinorelbine-tetrandrine Liposomes Modified with RGD and Study on the in vitro Antitumor Effect / 中国药房

OBJECTIVE:To prepare the vinorelbine-tetrandrine liposomes modified with RGD,and study the inhibitory effect on glioma C6 cells. METHODS:Film dispersion method and ammonium sulfate gradient method were used to prepare the vinorel-bine-tetrandrine liposomes modified with RGD,and the morphology and particle size distribution were observed. The vinorelbine content was determined,and sulforhodamine B method was used to respectively determine the inhibitory effects of blank targeting liposomes,normal vinorelbine liposomes and vinorelbine-tetrandrine liposomes modified with RGD on C6 cells. RESULTS:The prepared vinorelbine-tetrandrine liposomes modified with RGD were spherical or almost spherical with smooth surface,and particle size was about 120 nm. The average content of vinorelbine was 28.27 μg/mL(RSD=0.38％,n=3). Blank targeting liposomes had no significant effect on the growth of C6 cells;vinorelbine-tetrandrine liposomes modified with RGD can obviously inhibit the growth of C6 cells,and cell viability after its effect was significantly lower than normal vinorelbine liposomes (P<0.05). CON-CLUSIONS:Vinorelbine-tetrandrine liposomes modified with RGD are successfully prepared,and they show obvious inhibitory ef-fects on the growth of C6 cells.

Analysis of the efficacy of trastuzumab combined with vinorelbine therapy in the treatment of human epithelial growth factor recepeor-2 positive advanced breast cancer / 中国医师进修杂志

Objective To explore the clinical efficacy of trastuzumab combined with vinorelbine therapy in the treatment of advanced breast cancer with human epithelial growth factor receptor-2 (HER-2) positive.Methods From April 2010 to April 2013,91 advanced breast cancer patients who failed in the paclitaxel therapy received trastuzumab plus vinorelbine (45 cases,vinorelbine group) or capecitabine (46 cases,capecitabine group).The treatment efficacy,toxic effects and 3-year survival rate in two groups were compared.Results The clinical benefit rate in two groups had no significant difference (P ＞ 0.05),but objective response rates in vinorelbine group was higher than that in capecitabine group:44.44％(20/45) vs.23.91％(11/46),and there was significant difference (P =0.039).The toxic effects in two groups had no significant difference (P ＞ 0.05).The 3-year survival rate in two groups had no significant difference (P =0.252).Conclusions In the treatment of HER-2 positive advanced breast cancer,trastuzumab plus vinorelbine or capecitabine shows no significant differences in adverse reaction or in 3-year survival rate.However,trastuzumab plus vinorelbine shows better objective response rate compared with trastuzumab plus capecitabine.

Comparative of Therapeutic Efficacy and Safety of 3 Chemotherapy Regimens in the Treatment of Small Cell Esophageal Cancer / 中国药房

OBJECTIVE:To compare therapeutic efficacy and safety of different chemotherapy regimens in the treatment of small cell esophageal cancer. METHODS:In retrospective analysis,58 patients with small cell esophageal cancer were divided into group A(18 cases),B(26 cases)and C(14 cases)according to chemotherapy regimens. Group A was given Cisplatin injection 75 mg/m2 intravenously,d1-3+Paclitaxel injection 175 mg/m2,d1-3. Group B was given Cisplatin injection 30 mg/m2 intravenously,d1-3+Et-oposide injection 100 mg/m2,d1-3. Group C was given Vinorelbine tartrate injection 25 mg/m2 intravenously,d1-3+Gemcitabine hydro-chloride for injection 1000 mg/m2,d1-3. A treatment course of 3 groups lasted for 21 d,and they all received 2 cycles of treatment. Clinical efficacies,1,2,3-year survival rate and the incidence of Ⅲ-Ⅳ degree toxic reaction(cough,fever,expectoration,short-ness of breath,fatigue,chest pain,bone marrow suppression,gastrointestinal reactions) were compared among 3 groups. RE-SULTS:Total response rate and 1,2,3-year survival rate were in descending order:group C>group B>group A;the incidence of Ⅲ-Ⅳ degree cough,fever,expectoration,shortness of breath,fatigue,chest pain were in ascending order:group C0.05). CONCLUSIONS:Therapeutic efficacy and 1,2,3-year survival rate of vinorelbine combined with gemcitabine are significantly higher than those of cisplatin combined with paclitaxel or etoposide with better safety.

Efficacy of Aidi Injection () on overexpression of P-glycoprotein induced by vinorelbine and cisplatin regimen in patients with non-small cell lung cancer / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the efficacy of Aidi Injection () on overexpression of P-glycoprotein (P-gp) induced by vinorelbine and cisplatin (NP) regimen in patients with non-small cell lung cancer (NSCLC), and study the difference between intravenous administration and targeting intratumor administration of Aidi Injection with thoracoscope.</p><p><b>METHODS</b>Totally 150 patients with NSCLC were randomly assigned to the control group, the intravenous group and the intratumor group by the random envelope method, 50 cases in each group. The patients were treated with NP regimen (2 cycles), NP regimen (2 cycles) plus Aidi intravenous injection, or NP regimen (2 cycles) plus Aidi intratumor injection with thoracoscope, respectively for 6 weeks. The clinical effificacy was observed based on Response Evaluation Criteria in Solid Tumors (RECIST) rules, the expression of P-gp in the tumor tissue was tested before, 3 and 6 weeks after treatment, the safety was evaluated by monitoring the toxicity in the process of treatment, and the progression-free survival (PFS) was measured.</p><p><b>RESULTS</b>Fifteen cases dropped out because of the irreconcilable conditions which had no relationship with the treatment, 4 in the control group, 5 in the intravenous group, and 6 in the intratumor group, respectively. Compared with the control group, the response rates (complete remission + partial response) and the disease control rates (complete remission + partial response + stable disease) were significantly higher, the P-gp expressions were significantly decreased after 3 and 6 weeks of treatment, and the Kaplan-Meier survival curves of PFS were significantly longer in the intravenous and intratumor groups (P<0.05 or P<0.01), and the intratumor group showed better effects than the intravenous group (P<0.05 or P<0.01). Compared with the control group, the occurrences of rash, nausea and leukocytopenia were signifificantly decreased in the intravenous and intratumor groups (P<0.05), but without signifificant difference between the intravenous and intratumor groups (P>0.05).</p><p><b>CONCLUSION</b>Aidi Injection not only improves the effificacy of NP regime, but also has the function of reducing adverse events and preventing against overexpression of P-gp induced by chemotherapy of NP regimen.</p>

Clinical comparative study of vinorelbine and docetaxel separately combined with lobaplatin in treatment of recurrent and metastatic breast cancer / 中国基层医药

Objective To investigate clinical effect and safety difference of vinorelbine and docetaxel sepa-rately combined with lobaplatin in treatment of recurrent and metastatic breast cancer.Methods 160 patients with recurrent and metastatic breast cancer were chosen from July 2009 to July 2012 in our hospital,and they were random-ly divided into two groups,including A group (80 patients)with vinorelbine and B group (80 patients)with docetaxel on the basis of lobaplatin.The clinical efficacy for short -term,survival rate with follow -up and side effects incidence of both groups were compared.Results The RR and DCR of A group were 51.25%,68.75%,which of B group were 55.00%,71.25%.There was no significant difference in the clinical efficacy for short -term between the two groups (χ2 =1.04,2.37,all P >0.05).The survival rates in 1,2 and 3 years after treatment of A group were 60.00%,53.75%,28.75%,those of B group were 67.50%,57.50%,31.25%.There was no significant difference in the survival rate with follow -up between the two groups (χ2 =2.14,3.01,1.87,all P >0.05).The incidence rate of drug side effects of B group was significantly lower than A group(χ2 =13.14,9.33,15.74,11.65,8.29,all P <0.05).Conclusion Vinorelbine and docetaxel separately combined with lobaplatin in treatment of recurrent and metastatic breast cancer can efficiently control the disease progress and prolong the survival time;but docetaxel com-bined with lobaplatin treatment is helpful to reduce the risk of serious side effects.

Chemotherapy-induced Drug Reaction due to Extravasation of Vinorelbine / 대한피부과학회지

Vinorelbine, a vinca alkaloid anticancer drug, is widely used to treat various cancers. Several dermatological side effects of vinorelbine, such as acral erythema, phlebitis, and severe extravasation reactions, have been reported. Vinorelbine is categorized as non-DNA binding vesicant that undergoes high metabolism and clearance, which limits the degree of tissue injury if extravasation occurs. A 73-year-old male presented with erythematous linear patches on his left wrist and a 51-year-old male presented with erythematous eroded patches and bullae on his right forearm. Histopathologic study showed interface changes with basal vacuolar degeneration and epidermal dysmaturation. Separation of the dermis from the epidermis was observed, as well as interstitial and perivascular inflammatory infiltrates in the dermis. Both patients were being treated with vinorelbine for lung cancer. Before the onset of the skin lesions, accidental intravenous extravasation of vinorelbine had occurred. Herein, we report two cases of chemotherapy induced drug reaction due to extravasation of vinorelbine.

Concentration Determination of Inorelbine Bitartrate in Human Plasma by LC-MS/MS / 中国药房

OBJECTIVE:To establish a method for determining the concentration of vinorelbine bitartrate in human plasma, and study the pharmacokinetic process of vinorelbine in human plasma. METHODS:The samples were extracted with Solid-phase extraction(SPE). LC-MS/MS was performed on the column of Agilent Extend C18 with the mobile phase of 5 mmol/L ammonium ac-etate solution(pH10.5)-acetonitrile-methano1(18∶10∶72,V/V/V)at the flow rate of 0.4 ml/min,the ion source was ESI and MRM mode was used to scan positive ion detection. The ion reaction of quantitative analysis was m/z 779.50→m/z 122.10 (vinorelbine) and m/z 811.60→m/z 224.50 (internal standard, vinblastine). 3p97 was used to calculate the pharmacokinetic parameters. RE-SULTS:The determination was not interfered by endogenous impurities,and there was no matrix effect;the lowest limit of quantita-tive analysis was 2.0 ng/ml with the linear range of 2.0-4 000.0 ng/ml(r=0.997 8);the linear range of vinorelbine in plasma was. The intra-day and inter-day precisions and accuracy results were all in line with the acceptable limit across all concentrations. t1/2γ of 30 mg/m2,40 mg/m2 Vinorelbine Emulsion for Injection groups and 30 mg/m2 Vinorelbine for Injection group were(37.958 ± 34.256)、(47.835±54.231)、(76.873±40.537)h respectively,cmax were(1 426.250±397.562)、(1 700.125±624.669)、(2 187.500± 828.040)ng/ml respectively,AUC0-48 h were(75 839±19 551)、(82 088±14 207)、(95 318±18 208)mg·h/L respectively. CONCLU-SIONS:The method is rapid,sensitive and specific,and suitable for the determination of vinorelbine and pharmacokinetic study. Metabolic processes of vinorelbine can be described as first order process of three-compartment model in cancer patients.

Preparation and Characterization of Vinorelbine Bitartrate Long-circulation Liposome / 医药导报

Objective To prepare vinorelbine bitartrate long-circulation liposomes by pH gradient loading methods and make characterization. Methods The impact of hydration temperature and extrusion times on the blank liposome particle size was investigated;and the incubation temperature and in duration on size and encapsulation percentage of drug loading liposome particle was tested. The vinorelbine bitartrate long-circulation liposome was characterized for particle size,polydispersion index, Zeta potential,morphology,and was studied for long term stability. Results The particle size,Zeta potential,polydispersion in-dex of long-circulation liposomes were (96. 4±27. 2) nm,(0. 162±0. 042),(-26. 7±3. 5) mV,respectively. The liposomes were small,unilamellar and spherical with smooth surface under transmission electron microscopy. Long term stability studies showed that the liposomes were stable for up to 3 months after storage at 5 ℃ . Conclusion The preparation technology for the vinorel-bine bitartrate long-circulation liposome by pH gradient loading methods is feasible.

Pharmacokinetics study of long-circulation and thermosensitive liposome loaded vinorelbine bitartrate in beagle dogs / 军事医学

Objective To establish a quick method to analyze vinorelbine ( NVB) in plasma of beagle dogs and study its pharmacokinetics of long-circulation and thermosensitive liposome loaded vinorelbine bitartrate.Methods The plasma was treated with liquid-liquid extraction after precipitation in methanol.The analysis was perfomed on a Venusil XBP C18 column(2.1 mm ×50 mm, 3 μm) at 35℃,the mobile phase consisted of methanol and water( containing 10 mmol/L ammonium acetate, 1%acetonitrile) 80∶20 and injection volume was 10μl.The type of mass spectrum was multireactive monitoring(MRM) in a positive mode.The monitor transitions were m/z 779.4-765.4 for vinorelbine and m/z 825.4-122 for vincristine.Results The concentration range from 10 to 2500 ng/ml had a good linearity ( r=0.0994).The precision, accuracy and extraction efficiency were acceptable.The plasma samples were stable for 10 days at -20℃ and 24 h at room temperature.Pharmacokinetic study in beagle dogs showed that the main parameters for injection and liposome were Cmax(833.51 ±150.42) and (1397.95 ±443.05)ng/ml, AUC(0-t) (577.16 ±223.57) and (1059.82 ±408.27) ng/ml· h, Cl(3014.64 ±1049.17)and 1633.10 ±551.77 ml/(h· kg), respectively.Conclusion A reliable HPLC-MS/MS method for vinorelbine analysis is established and can be applied to the pharmacokinetics study of liposome.The results show that liposome has a higher AUC, Cmax and longer Cl than injection.Meanwhile, liposome has a lower irritability.