An analysis of studies on non-small cell lung cancer registered on clinical trials registry of India

Background: Lung cancer is the most common cancer in males, of which non-small cell type is more prevalent. It is an active area of research owing to the limited available treatment modalities with several studies registered on CTRI. Objectives of current study was to analyse randomized control trials for non-small cell lung cancer registered on clinical trial registry India., , Methods: Studies registered on CTRI were reviewed in this registry-based audit using the keywords lung cancer and non-small cell lung cancer. Parameters such as type of study, nature of intervention, phase of study, primary and secondary endpoints used, etc, were analysed and summarised using descriptive statistics in Microsoft Excel 365., , Results: Out of 230 trials for lung cancer, 121 studied non-small cell lung cancer, of which 103 studies (85.1%) were interventional studies. Most common intervention under study was drug 97 studies (94.2%) followed by radiation 4 studies (3.3%). Majority of trials were phase 3, 48 trials (39.7%) and only 4 (3.3%) studies were phase 1. Five most common primary and secondary endpoints observed were survival, response rate, safety, pharmacokinetic data & quality of life. Maximum patients were in the advanced stage of cancer(52.1%) and pemetrexed (9.9%) was the most common drug used., , Conclusions: We observed an increasing trend in studies registered on CTRI, with maximum studies in phase 3 with patients in the advanced stage of cancer having overall survival as the endpoint

Effects of centralized volume-based procurement policy on the use of drugs for non-small cell lung cancer in a third-grade class-A cancer hospital / 中国药房

OBJECTIVE To analyze the effects of centralized volume-based procurement policy （hereinafter referred to as “centralized procurement”） on the use of anti-tumor drugs in medical institutions. METHODS The interrupted time series model was used to analyze the changes in the monthly purchase volume and purchase amount of docetaxel， gemcitabine and pemetrexed disodium in a third-grade class-A cancer hospital in Shanxi province from January 2018 to December 2021. RESULTS & CONCLUSIONS After the implementation of the centralized procurement policy， both the selected drugs and the non-selected drugs had different degrees of price reduction， and the price reduction of the selected drugs was far greater than that of the non- selected drugs； average monthly purchase volume and amount of docetaxel decreased significantly in that month after the implementation of the policy， while those of gemcitabine and pemetrexed disodium increased significantly （P＜0.05 or P＜0.01）. After the implementation of the policy， the average monthly purchase volume and amount of gemcitabine showed a downward trend， while those of docetaxel and pemetrexed disodium showed an upward trend （P＜0.05 or P＜0.01）. It is suggested that hospitals should strengthen pharmaceutical administration， and avoid adopting a “one size fits all” approach to non-selected drugs； relevant departments should further expand the collection range of anti-tumor drugs or carry out special collection of anti-tumor drugs， so as to save medical insurance funds and reduce medical expenses.

Pemetrexed clinical trial for intrathecal injection chemotherapy based on cerebrospinal fluid pharmacokinetics in patients with leptomeningeal metastasis from lung adenocarcinoma / 国际肿瘤学杂志

Objective:To investigate the pharmacokinetics of cerebrospinal fluid pemetrexed following intrathecal injection chemotherapy in patients with leptomeningeal metastasis (LM) from lung adenocarcinoma and provide a basis for clinical intrathecal injection chemotherapy.Methods:A total of 21 patients with lung adenocarcinoma LM who underwent pemetrexed intrathecal injection chemotherapy via Ommaya capsule at Nanjing Drum Tower Hospital, Aiffilitated Hospital of Nanjing University Medical School from November 2019 to November 2022 were collected, and divided into 30, 40 and 50 mg groups ( n=10, n=4, n=7) according to pemetrexed dose. Cerebrospinal fluid was collected at 0, 0.5, 1, 2, 4, 6, 12, 24 and 48 h after the first intrathecal injection chemotherapy, and day 8 of each cycle for three groups. Reversed phase high performance liquid chromatography was used to determine the drug concentration in cerebrospinal fluid, to clarify the drug-related pharmacokinetic parameters, and to compare the differences in pemetrexed concentration among groups. Finally, cerebrospinal fluid pemetrexed concentration changes were observed and compared after different intrathecal injection chemotherapy cycles. Results:There were statistically significant differences in cerebrospinal fluid drug concentrations of patients in three groups at 0, 0.5, 1, 2, 4, 6, 12, 24 and 48 h after the first intrathecal injection chemotherapy (30 mg group: F=20.56, P<0.001; 40 mg group: F=27.06, P<0.001; 50 mg group: F=28.63, P<0.001), and there were statistically significant differences in the concentration of cerebrospinal fluid drugs in each dose group at 0.5, 1, 2, 4, 6 and 12 h compared to 0 h after intrathecal injection chemotherapy (all P<0.05). Compared to the 30 mg group, cerebrospinal fluid drug concentrations in the 50 mg group increased at 1, 2, 4, 6, 12 and 24 h after intrathecal injection chemotherapy, with statistically significant differences (all P<0.05). Pharmacokinetic analysis of cerebrospinal fluid pemetrexed showed that area under the concentration-time curve (AUC) 0-∞ of the 30, 40 and 50 mg groups were (5 696.12±283.32), (7 886.29±396.57), and (14 202.70±440.19) h·mg/L, respectively, with a statistically significant difference ( F=1 159.00, P<0.001) ; AUC 0-∞ increased in the 50 mg group compared to the 30 and 40 mg groups (both P<0.05) ; AUC 0-∞ increased in the 40 mg group compared to the 30 mg group ( P<0.05). The half-lives of three groups were (8.75±0.23), (11.29±0.59) and (16.42±1.23) h, respectively, with a statistically significant difference ( F=206.80, P<0.001) ; half-life was longer in the 50 mg group compared to the 30 and 40 mg groups (both P<0.05) ; half-life was longer in the 40 mg group compared to the 30 mg group ( P<0.05). The peak time of three groups were (1.55±0.10), (1.00±0.01), (1.43±0.11) h, respectively, with a statistically significant difference ( F=48.11, P<0.001) ; the peak time was shorter in the 40 and 50 mg groups compared to the 30 mg group (both P<0.05). Clearance of three groups were (7.02±2.46), (5.80±1.25) and (3.66±1.32) L/h, respectively, with a statistically significant difference ( F=6.02, P=0.009) ; clearance was decreased in the 50 mg group compared to the 30 mg group ( P<0.05). The peak concentration of three groups were (540.45±32.25), (820.75±46.47) and (1 014.78±64.96) mg/L, respectively, with a statistically significant difference ( F=207.70, P<0.001) ; peak concentration increased in the 50 mg group compared to the 30 and 40 mg groups (both P<0.05) ; peak concentration increased in the 40 mg group compared to the 30 mg group ( P<0.05). Cerebrospinal fluid drug concentrations were dynamically monitored after 4 cycles of intrathecal injection chemotherapy, in which cerebrospinal fluid pemetrexed concentrations in 30 mg group were (13.76±4.79), (11.41±7.08), (9.41±2.59) and (7.86±4.02) mg/L, respectively; 40 mg group were (14.45±6.59), (12.87±15.73), (11.24±2.48) and (9.09±3.38) mg/L, respectively; 50 mg group were (12.94±10.34), (9.72±7.62), (8.15±8.17) and (4.34±4.21) mg/L, respectively. There was a statistically significant difference in cerebrospinal fluid drug concentrations among different intrathecal injection chemotherapy cycles in 30 mg group ( F=4.04, P=0.016), and the cerebrospinal fluid drug concentration decreased in cycles 3 and 4 compared to cycle 1 (both P<0.05). There were no statistically significant differences in cerebrospinal fluid drug concentrations among different treatment cycles in 40 and 50 mg groups ( F=0.28, P=0.837; F=3.57, P=0.066) . Conclusion:Reversed phase high performance liquid chromatography method can effectively detect the pemetrexed concentration in cerebrospinal fluid; dynamic monitoring of cerebrospinal fluid pemetrexed concentration can provide a basis for the dosage and the treatment cycle of intrathecal injection chemotherapy in LM patients with lung adenocarcinoma.

Analysis of the Efficacy of Pemetrexed Maintenance Therapy in Patients with Malignant Pleural Mesothelioma / 中国肺癌杂志

BACKGROUND@#Malignant pleural mesothelioma (MPM) is a highly aggressive disease arising from pleural mesothelial cells. Advanced pleural mesothelioma has a poor prognosis, with a median survival of no more than 15 months. First line standard chemotherapy regimen recommended is Pemetrexed based chemotherapy regimen, with or without bevacizumab. There is no consensus on whether patients who have received first-line standard chemotherapy can benefit from pemetrexed maintenance chemotherapy. The study aimed to investigate the efficacy and safety of pemetrexed maintenance therapy (PMT) after treatment with a pemetrexed and platinum regimen for patients with MPM.@*METHODS@#A total of 40 MPM patients were collected from Cancer Hospital Chinese Academy of Medical Sciences from January 2013 to January 2018, eligible patients were unresectable MPM, without disease progression following 4 to 6 cycles of pemetrexed and platinum, including pemetrexed maintenance therapy group (22 cases) and observation group (18 cases). The last follow-up was conducted in January 2020. The primary endpoint were progression free survival (PFS), and the secondary end points were overall survival (OS), the efficacy, adverse reactions of PMT.@*RESULTS@#The median PFS in the PMT arm was longer than that in the observation arm (8.5 mon vs 3 mon, P=0.008), but there was no significant difference in median OS (26.4 mon vs 15.7 mon, P=0.177). Objective response rate (ORR) of two group were 22.7% and 0%, respectively. The grade 3-4 toxicity in PMT group included grade 4 neutropenia in 1 patient (4.5%), grade 3 neutropenia in 1 patient (4.5%), grade 4 anemia in 1 patient (4.5%) and grade 3 nausea and anorexia in 1 patient (4.5%).@*CONCLUSIONS@#Pemetrexed maintenance therapy following initial pemetrexed and platinum chemotherapy improve PFS in patients with MPM, and is well tolerated.

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.

Clinical trials on intrathecal pemetrexed treated leptomeningeal metastases from solid tumors / 中华肿瘤杂志

Objective: To investigate the feasibility, safety and efficacy of intrathecal pemetrexed (IP) treated for patients with leptomeningeal metastases (LM) from solid tumors. Methods: Forty-seven patients receiving pemetrexed intrathecal chemotherapy in the First Hospital of Jilin University from 2017 to 2018 were selected. The study of pemetrexed intrathecal chemotherapy adopted the classical dose-climbing model and included 13 patients with meningeal metastasis of non-small cell lung cancer who had relapsed and refractory after multiple previous treatments including intrathecal chemotherapy. Based on the dose climbing study, 34 patients with meningeal metastasis of solid tumor who did not receive intrathecal chemotherapy were enrolled in a clinical study using pemetrexed as the first-line intrathecal chemotherapy combined with radiotherapy. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for influencing factor analysis. Results: The dose climbing study showed that the maximum tolerated dose of pemetrexed intrathecal chemotherapy was 10 mg per single dose, and the recommended dosing regimen was 10 mg once or twice a week. The incidence of adverse reactions was 10 cases, including hematological adverse reactions (7 cases), transaminase elevation (2 cases), nerve root reactions (5 cases), fatigue and weight loss (1 case). The incidence of serious adverse reactions was 4, including grade 4-5 poor hematology (2 cases), grade 4 nerve root irritation (2 cases), and grade 4 elevated aminotransferase (1 case). In the dose climbing study, 4 patients were effectively treated and 7 were disease controlled. The survival time was ranged from 0.3 to 14.0 months and a median survival time was 3.8 months. The clinical study of pemetrexed intrathecal chemotherapy combined with radiotherapy showed that the treatment mode of 10 mg pemetrexed intrathecal chemotherapy once a week combined with synchronous involved area radiotherapy 40 Gy/4 weeks had a high safety and reactivity. The incidence of major adverse reactions was 52.9% (18/34), including hematologic adverse reactions (13 cases), transaminase elevation (10 cases), and nerve root reactions (4 cases). In study 2, the response rate was 67.6% (23/34), the disease control rate was 73.5% (25/34), the overall survival time was ranged from 0.3 to 16.6 months, the median survival time was 5.5 months, and the 1-year survival rate was 21.6%. Clinical response, improvement of neurological dysfunction, completion of concurrent therapy and subsequent systemic therapy were associated with the overall survival (all P<0.05). Conclusions: Pemetrexed is suitable for the intrathecal chemotherapy with a high safety and efficacy. The recommended administration regimen was IP at 10 mg on the schedule of once or twice per week. Hematological toxicity is the main factor affecting the implementation of IP. Vitamin supplement can effectively control the occurrence of hematological toxicity.

Investigation of the API distribution homogeneity in lyophilized product-pemetrexed disodium for injection by confocal micro-Raman spectroscopy mapping / 药学学报

The method of homogeneity evaluation for active pharmaceutical ingredient (API) spatial distribution in lyophilized product was investigated for the first time with confocal micro-Raman spectroscopy mapping, using pemetrexed disodium for injection as a model drug. Certain areas of the lyophilized product were scanned to obtain Raman spectra. The classical method ("peak clipping" method) was employed for mapping with characteristic Raman peaks of the API and the excipient. Due to the API being finely dispersed in the excipient in lyophilized products, the classical method cannot discriminate between the two ingredients making the distribution homogeneity difficult to evaluate. The "ratio of characteristic peak intensities" method was then utilized. Using this method, the relative intensity of the characteristic Raman peaks of the API to the excipient was applied for mapping and the relative content of API to excipient was calculated for a homogeneity evaluation of the drug distribution. The validation of this method showed a good linear relationship between the relative intensity and the relative content of API to excipient (r2 > 0.99), and the precision and recovery were adequate for homogeneity evaluation of API by Raman spectroscopy mapping. Five products of pemetrexed disodium for injection from different manufacturers were tested through Raman maps applying this method and the histograms of relative Raman intensity were also plotted by frequency to help the homogeneity evaluation of drug distribution. The results showed that there were obvious differences in the drug distribution homogeneity from different products, where a more homogeneous API distribution was found in the brand product. This research provides a reliable method for the homogeneity evaluation of API distribution, which facilitates quality evaluation and process optimization of lyophilized products.

Significance of serum miRNA-126 and miRNA-449a expression levels in the therapeutic efficacy and prognostic evaluation of pemetrexed combined with cisplatin for treatment of non-small cell lung cancer / 肿瘤研究与临床

Objective:To investigate the effects of serum miRNA-126 (miR-126) and miRNA-449a (miR-449a) expression levels on the efficacy and prognostic evaluation of pemetrexed combined with cisplatin in treatment of non-small cell lung cancer (NSCLC).Methods:The data of 100 NSCLC patients admitted to Wuhan Hankou Hospital from January 2016 to January 2017 were retrospectively analyzed. Before treatment, the relative expression levels of miR-126 and miR-449a in serum of both groups were detected by using real-time fluorescence quantitative polymerase chain reaction. A total of 100 healthy volunteers during the same period were treated as the control group. The efficacy was evaluated after 2 courses of treatment, and the correlation of miR-126 and miR-449a relative expression levels with clinicopathological characteristics, efficacy and prognosis of patients was analyzed.Results:The relative expression levels of serum miR-126 and miR-449a in NSCLC patients were lower than those in the control group (1.23±0.34 vs. 2.22±0.57, 0.95±0.21 vs. 2.13±0.43), and the differences were statistically significant ( F = 14.92, 24.66; all P < 0.01). There were significant differences in the relative expression levels of serum miR-126 and miR-449a in NSCLC patients with different therapeutic effects ( F = 80.65, 22.43, all P < 0.01). Spearman correlation analysis showed that the relative expression levels of serum miR-126 and miR-449a were correlated with the therapeutic effect ( ρ = 0.782, 0.618, all P < 0.01). The relative expression levels of serum miR-126 and miR-449a in NSCLC patients with different gender and age had no statistically significant difference (all P > 0.05). The relative expression levels of serum miR-126 and miR-449a in NSCLC patients with different TNM staging, pathological type, tumor diameter, degree of differentiation showed significant differences (all P < 0.05). Univariate Cox regression analysis showed TNM staging, tumor diameter, degree of differentiation, relative expression levels of serum miR-126 and miR-449a were correlated with the survival of NSCLC patients (all P < 0.05). Multivariate Cox regression analysis revealed TNM staging, tumor diameter, degree of differentiation and the relative expression levels of miR-126 and miR-449a were independent factors affecting the survival of NSCLC patients after surgery. The overall survival of patients with the high expressions of miR-126 and miR-449a was better than that of patients with the low expressions (all P < 0.05). Conclusions:The relative expression levels of serum miR-126 and miR-449a can be used as a potential serologic indicator to analyze the prognosis of NSCLC patients treated with pemetrexed combined with cisplatin.

Mesotelioma en paciente colombiano con sobrevida mayor a tres años: presentación de caso / Mesothelioma in a Colombian Patient over three years: Case Presentation / Mesotelioma em paciente colombiano com sobrevivência superior a três anos: apresentação de caso

Resumen Introducción: el mesotelioma epitelioide es un tumor que se desarrolla en las capas embrionarias mesoteliales; es de etiología desconocida, pero se relaciona con la exposición al asbesto, con una presentación clínica inespecífica y con un pronóstico de sobrevida corto después del diagnóstico. Presentación del caso: hombre de profesión mecánico automotor, con tos sin expectoración, disnea, hipertermia y emaciación posterior a la extracción quirúrgica de lipomas que afectaban el tórax, quien posteriormente fue diagnosticado con mesotelioma epitelioide maligno con ubicación en la pleura del hemitórax derecho y fue tratado con toracotomía, quimioterapia con los medicamentos pemetrexed y cisplatino y sesiones de radioterapia, que mostraron un aumento en la sobrevida 3 tres años. Conclusión: este caso permitió identificar que el uso de la pleurodesis química con quimioterapia como tratamiento podría ser responsable del aumento de la esperanza de vida y la calidad de esta en los pacientes que padecen este tipo de tumor.

Abstract Introduction: Epithelioid mesothelioma is a tumor that develops in the mesothelial embryonic layers; it is of an unknown etiology, but it is related to asbestos exposure with a nonspecific clinical presentation and a short survival prognosis after diagnosis. Case presentation: An automotive mechanic patient presents with cough without expectoration, dyspnea, hyperthermia, and emaciation following surgical removal of lipomas. This affected the chest and the patient was subsequently diagnosed with malignant epithelioid mesothelioma located in the pleura of the right hemithorax. The patient was treated with thoracotomy, chemotherapy with the drugs pemetrexed and cisplatin, and radiation therapy sessions which resulted in an increased survival rate at 4 years. Conclusion: This case report identifies the use of chemical pleurodesis in combination with chemotherapy as an effective treatment for increasing the life expectancy and quality of life in patients suffering from this type of tumor.

Resumo Introdução: o mesotelioma epitelióide é um tumor que se desenvolve nas camadas embrionárias mesote-liais; é de causa desconhecida, mas está relacionado com a exposição ao amianto e possui uma manifestação clínica inespecífica e com prognóstico de sobrevivência curto após o diagnóstico. Apresentação do caso: o paciente é um mecânico automotivo, que apresentou tosse seca, dispneia, hipertermia e emagrecimento posterior a extração cirúrgica de lipomas que afetavam o tórax sendo posteriormente diagnosticado com mesotelioma epitelióide maligno localizado na pleura do hemitórax direito e foi tratado com toracotomia, quimioterapia com os medicamentos pemetrexed e cisplatino além de sessões de radioterapia, mostrando um aumento de expectativa de vida para 4 anos. Conclusão: este estudo de caso permite identificar que o uso da pleurodese química com quimioterapia como tratamento poderia ser a responsável pelo aumento da expectativa e qualidade de vida em pacientes acometidos por este tipo de tumor.

Clinical observation of albumin-bound paclitaxel or pemetrexed combined with cisplatin in the treatment of advanced mutation negative lung adenocarcinoma / 国际肿瘤学杂志

Objective:To compare the short-term clinical efficacy, adverse reactions and pharmacoeconomics of advanced mutation negative lung adenocarcinoma treated by albumin-bound paclitaxel or pemetrexed combined with cisplatin.Methods:From September 2019 to October 2020, 80 patients with advanced lung adenocarcinoma diagnosed in the First Affiliated Hospital of Bengbu Medical College were divided into observation group and the control group according to the randomized digital table, with 40 cases in each group. The observation group received albumin-bound paclitaxel combined with cisplatin, and the control group received pemetrexed combined with cisplatin. After 2 cycles of treatment, the short-term efficacy and the adverse reactions of the two groups were evaluated. The cost of chemotherapy drugs and the average length of hospital stay were compared between the two groups.Results:The objective response rates of the observation group and the control group were 30.0% (12/40) and 32.5% (13/40), the disease control rates were 77.5% (31/40) and 82.5% (33/40) respectively, and there were no significant differences ( χ2=0.058, P=0.809; χ2=0.313, P=0.576). The adverse reactions of the two groups were mainly grade Ⅰ-Ⅱ. The incidences of leucopenia, neutropenia, thrombocytopenia, hemoglobin decreased, gastrointestinal reaction, liver function damage and renal function damage in the observation group were 20.0% (8/40), 20.0% (8/40), 20.0% (8/40), 17.5% (7/40), 37.5% (15/40), 12.5% (5/40) and 7.5% (3/40) respectively, those in the control group were 25.0% (10/40), 20.0% (8/40), 17.5% (7/40), 15.0% (6/40), 32.5% (13/40), 17.5% (7/40) and 5.0% (2/40) respectively, and there were no statistically significant differences between the two groups ( χ2=0.287, P=0.592; χ2<0.001, P>0.999; χ2=0.082, P=0.775; χ2=0.092, P=0.762; χ2=0.220, P=0.639; χ2=0.392, P=0.531; χ2<0.001, P>0.999). The median cost of chemotherapy drugs and the median length of hospital stay in the observation group were 7 453 yuan and 6 days respectively, which were less than 8 956 yuan and 7 days in the control group, with statistically significant differences ( Z=-3.057, P=0.002; Z=-2.733, P=0.006). Conclusion:The short-term efficacy of albumin-bound paclitaxel combined with cisplatin is equal to pemetrexed combined with cisplatin in treatment of advanced mutation negative lung adenocarcinoma, and the adverse reactions are similar. However, the average cost of chemotherapy drugs of albumin-bound paclitaxel combined with cisplatin is less than pemetrexed combined with cisplatin, and the average length of hospital stay is shorter.

Prospective study of preliminarily diagnosed primary central nervous system lymphoma treated with an R-FPD regimen / 中国肿瘤临床

Objectives: To evaluate the safety, efficacy, and feasibility of using rituximab in combination with fotemustine, pemetrexed, and dexamethasone (R-FPD) in primary central nervous system lymphoma (PCNSL). To undertake an initial exploration of the significance of biomarkers in PCNSL. Methods: This was a prospective, single-center, single-arm, phase Ⅱ clinical trial. Patients newly diagnosed with PCNSL from the First Affiliated Hospital of Zhengzhou University from July 2018 to July 2019 were enrolled. All patients underwent first-line chemotherapy with R-FPD. The primary study endpoints were: objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). The secondary study endpoint was: adverse reactions (ADR). Results: Twelve patients were included in the study. After four cycles of treatment, six patients had complete remission, two had partial remission, one was stable, and three progressed. The ORR was 66.7%, DCR was 75%, and median PFS was 7 months (95% confidence interval: 4.4-9.6 months). The median OS was 10.5 months (95% confidence interval: 6.1-14.9 months). The main adverse reaction due to R-FPD chemotherapy was hematologic toxicity, and grade III- neutropenia and thrombocytopenia were observed (16.7% and 25%, respectively). High expression of c-myc protein (>40%) did not appear to be significantly associated with prognosis. Conclusions: R-FPD is an effective and safe protocol for the treatment of newly diagnosed PCNSL patients. There was no significant relationship between high c-myc expression and prognosis.

Successful treatment of metastatic extramammary Paget's disease with pemetrexed monotherapy systemically and 5-fluorouracil topically

Advanced extramammary Paget's disease does not have a standardized treatment guideline as its incidence is low and has been rarely reported in literature. Here we describe a case of metastatic extramammary Paget's disease successfully treated with topical 5-fluorouracil (5-FU) and systemic pemetrexed. The therapy was safe without any appreciable adverse effects like diarrhea, rash, neutropenia or fatigue; maintaining remission for more than 6 months. Thus, we propose 5-FU and pemetrexed as the first-line therapy for advanced extramammary Paget's disease, especially for aged patients with unresectable skin lesions.

Efficacy of apatinib plus pemetrexed for advanced non-squamous non-small cell lung cancer in elderly patients / 中国肿瘤临床

Objective: To examine the efficacy and safety of pemetrexed plus apatinib for the treatment of advanced non-squamous non-small cell lung cancer (NSCLC) in elderly patients. Methods: Between January 2016 and June 2017, 38 elderly patients with ad-vanced non-squamous NSCLC from Qingdao Municipal Hospital were examined. All patients received first-or second-line therapy. The inclusion criteria were an age of≥65 years, physical status score of 0-2, and expected survival time of>3 months. Eighteen patients were assigned to the test group, and the remaining 20 patients were assigned to the control group. The patients in the test group were treated with pemetrexed plus apatinib, pemetrexed 500 mg/m2 on day 1 and apatinib 250 mg/d on days 1-21. The control group re-ceived pemetrexed in a 21-day cycle until the disease progressed or intolerable adverse reactions developed. The study was reviewed and approved by the medical ethics committee of Qingdao Municipal Hospital. Results: The disease control rates in the test and con-trol groups were 72.2% and 35%, respectively, with a statistically significant difference (χ2=5.265, P=0.022). The median progression-free survival time (PFS) in the test and control groups were 5.7 months [95% confidence interval (CI): 2.8-8.6] and 3.1 months (95% CI:2.7-3.5), with a statistically significant difference (χ2=4.01, P=0.045). The difference in the incidence of hand-foot syndrome and hyper-tension between the two groups was statistically significant (P=0.007 and P=0.016, respectively), with side effects of 1 or 2 degree in most cases, which was acceptable. Conclusions: Pemetrexed plus apatinib has a definite curative effect on advanced NSCLC, with con-trollable adverse reactions.

Clinical observation of bevacizumab combined with pemetrexed for patients with re-current metastatic cervical cancer / 中国肿瘤临床

Objective: To observe the short-term efficacy and side effects of bevacizumab combined with pemetrexed for the treat-ment of recurrent and metastatic cervical cancer. Methods: The clinical data of 32 patients with recurrent metastatic cervical cancer admitted to the Department of Oncology, Guizhou Provincial People's Hospital between January 2014 and December 2016 were retro-spectively analyzed. All patients were treated with bevacizumab plus pemetrexed. In the 21-day cycle, chemotherapy was adminis-tered for 4 to 6 cycles. The efficacy and grade of adverse reactions were evaluated. Results: Of the 32 patients with cervical cancer, 0 had complete remission, 7 (21.9%) had partial remission, 19 (59.4%) had stable disease, and 6 (18.7%) had disease progression. The ef-fective rate was 21.9% (7/32) and the disease control rate was 81.3% (26/32). The 32 patients had mild common adverse reactions, which can be tolerated. Conclusions: Bevacizumab combined with pemetrexed has good short-term effects for patients with recurrent and metastatic cervical cancer, and its side effects can be tolerated. The long-term efficacy warrants further study.

Clinical Observation of Crizotinib in the Treatment of ALK Positive Advanced Lung Adenocarcinoma / 中国药房

OBJECTIVE： To observe the efficacy and safety of crizotinib in the treatment of anaplastic lymphoma kinase （ALK） positive advanced lung adenocarcinoma. METHODS： From Aug. 2015 to May 2017， 72 patients with ALK positive advanced lung adenocarcinoma were selected from our hospital. According to the simple random method， the patients were divided into control group and observation group， with 36 patients in each group. The control group was given Pemetrexed disodium for injection 500 mg/m2，d1， ivgtt+ Cisplatin for injection 75 mg/m2，d1-3，ivgtt； Dexamethasone acetate tablets 0.75 mg were given orally one day before administration， once in the morning and again in the evening； 7 days before administration， Folic acid tablets 0.4 mg were given orally till 21 days after the last administration of cisplatin； Vitamin B12 1 mg injection was injected intramuscularly every 3 weeks after intramuscular injection of cisplatin. Isotonic Glucose injection 100 g was intravenously dripped 1 day before medication； on the day of chemotherapy， isotonic Sodium chloride injection or Glucose injection was infused intravenously for 3 000-3 500 mL； at the same time， Potassium chloride injection 0.5 g， Mannitol injection 50 g， Furosemide injection 20 mg were given to ensure daily urine volume of 2 000-3 000 mL； a treatment course lasted for 21 d， and there were 2 courses in total. Observation group was additionally given Crizotinib capsules 250 mg orally， once at 7：00 in the morning and evening， swallowing whole capsule， not chewed or dissolved， for 42 days. The clinical efficacies， survival quality and the occurrence of toxic reaction were observed in 2 groups. RESULTS： Total response rate （61.11％） and stable rate of survival quality （83.33％） in observation group were significantly higher than those （27.78％， 44.44％） of control group （P＜0.05）； incidence of grade Ⅰ-Ⅳ myelosuppression， gastrointestinal reaction， abnormal liver function， peripheral neuritis and alopecia in observation group were significantly lower than those of control group； incidence of grade Ⅰ-Ⅳ visual effect in observation group was significantly higher than control group（P＜0.05）. There was no statistical significance in the incidence of edema between 2 groups（P＞0.05）. CONCLUSIONS： Based on routine chemotherapy， additional application of crizotinib can significantly improve therapeutic efficacy of patients with advanced ALK positive lung adenocarcinoma， and effectively improve survival quality of patients without increasing the occurrence of toxic reaction of other tissues or organs， but the incidence of toxic reaction is in high level relatively.

Efficacy and survival analysis of first-line and sequential maintenance chemotherapy in elderly patients with non-small cell lung cancer / 中国医师杂志

Objective To analyse the clinical effect and safety of Alimta (Pemetrexed) combined with cisplatin treatment (PP) on elderly patients with non small cell lung cancer (NSCLC).Methods We retrospectively analyzed the clinical data of 40 cases of NSCLC patients treated with Pemetrexed combined with cisplatin for first-line chemotherapy,and 24 cases of them continually received single Pemetrexed for maintenance treatment (PP + C).Then we compared the results with 35 patients in the non-Pemetrexed regimen (control group) and 26 patients with best supportive care (BSC) in the same period.The adverse reactions and short-term efficacy [response rate (RR),disease control rate (DCR)] were evaluated.Time to progression (TTP),median survival time (MST),one-year and three-year survival rates and follow-up overall survival (OS) were calculated.Results Among 40 patients with Pemetrexed regimen,2 patients had complete remission (CR),and the RR was 47.8％,which was better than 42.8％ (P =0.026) in the control group.The main adverse reactions of pemetrexed regimen were myelosuppression,fatigue,nausea and vomiting,but all were tolerated and no treatment-related death occurred.24 patients received single Pemetrexed maintenance therapy.The MST of the PP + C group was superior to the other groups (P =0.03,P ≤0.05);the median OS of the PP + C group,the control group,and the BSC group reached 13.2,10.4 months and 8.6 months,respectively (P ≤ 0.001).Conclusions For elderly patients with advanced NSCLC,especially adenocarcinoma,the combination of Pemetrexed and cisplatin is a better treatment option.It is convenient to administer and has less toxicity and adverse reactions related to chemotherapy.Patients with better PS score after first-line treatment can obtain longer survival period after maintenance treatment.

Association of genetic polymorphis of thymidylate synthase and methylene tetrahydro folate reductase with therapeutic effect of pemetrexed for treating advanced lung adenocarcinoma patients / 实用医学杂志

Objective To investigate the expressions of thymidylate synthase (TS) and methylene tetrahydrofolate reductase (MTHFR) polymorphisms and the therapeutic efficacy of chemotherapy with pemetrexed and platinum in advanced lung adenocarcinoma patients. Methods Fifty-eight patients with advanced lung adenocarcinoma were enrolled in this study. The blood samples from 25 of them were examined for extraction of DNA. The associations of the gene polymorphisms with the chemotherapy efficacy and PFS were analyzed. Results Disease control rate was noted by 38％ and the median time of progression-free survival was 8.1 months among 58 patients.There were 16％, 32％, 52％, and TS genotypes as 2R/2R, 2R/3R and 3R/3R respectively; the difference in the control rate between those with TS gene of 3R/3R and those with TS gene of R/2R+2R/3 R was significant statistically (53.8％ vs. 91.7％, P = 0.046) , but the difference in PFS was statistically insignificant (9.3 vs. 10.4 months, P> 0.05). There were 40％, 52％, 8％, and MTHFR genotypes as CC, CT and TT respectively. The DCR in those with MTHFR CC and C/T + T/T was 70％ and 73.3％, respectively and PFS was 10 months and 9.7 months respectively, showing no significant difference (P> 0.05). Conclusion The TS gene polymorphism is associated with therapeutic effect of pemetrexed for advanced lung adenocarcinoma, but MTHFR is not.

Clinical efficacy analysis of pemetrexed combined with gefitinib in treatment of advanced non-small cell lung cancer after epidermal growth factor receptor-tyrosine kinase inhibitor drug resistance / 肿瘤研究与临床

Objective To investigate the clinical efficacy of pemetrexed alone or combined with gefitinib in treatment of advanced non-small cell lung cancer (NSCLC) after epidermal growth factor receptortyrosine kinase inhibitor (EGFR-TKI) drug resistance.Methods The clinical data of 80 patients with advanced NSCLC after EGFR-TKI drug resistance from August 2014 to April 2018 were retrospectively analyzed.They were divided into two groups according to their treatment regimens:40 patients received pemetrexed alone (the control group) and 40 patients received pemetrexed combined with gefitinib (the observation group).The recent clinical efficacy,adverse reactions and the survival time of both groups were compared.The count data was compared by using x2 test or Fisher exact test.Kaplan-Meier method was used to make survival analysis and log-rank method was used to detect.Results The total effective rate of the observation group was higher than that of the control group [70.0％ (28/40) vs.32.5％ (13/40),x2 =11.257,P =0.001].There was no statistical difference in the adverse reactions [17.5％ (7/40) vs.20.0％ (8/40),x2 =0.082,P =0.775].The median progression-free survival time and median overall survival time of the observation group were longer than those of the control group (6.5 months vs.3.5 months,15.5 months vs.8.5 months,all P ＜ 0.01).Conclusion Pemetrexed combined with gefitinib has a recent favorable effect in advanced NSCLC after EGFR-TKI drug resistance,including low incidence of adverse reactions and prolonged survival time,which is worthy of further application.

Use of Ommaya Reservoirs to Deliver Pemetrexed in Leptomeningeal Metastasis from Non-small Cell Lung Cancer: A Case Report and Review of the Literature / 中国肺癌杂志

Leptomeningeal metastasis (LM) is one of the most severe complications of non-small-cell lung cancer (NSCLC), and its incidence is increasing gradually with the progress of targeted therapies. There are currently no standard guidelines for the therapy of LM. Intrathecal chemotherapy is the mainstay of treatment for NSCLC patients with LM, but the optimal drug, administration route and mode, and dosage remain unclear. We report a case of LM from NSCLC, who received the intrathecal chemotherapy with pemetrexed by Ommaya reservoir after prior targeted therapies. This local treatment improved the quality of life, and obtained the clearing of CSF cytology and stable lesions of LM without any notable side effects. After confirmation of LM, the patient has survived 17 months until now. Here we report the first case to demonstrate the potential effectiveness of intrathecal pemetrexed by Ommaya reservoir for the treatment of LM of NSCLC, summarize the safety and effectiveness of intrathecal chemotherapy in combination with related literatures, and provide a new strategy for local treatment of LM in clinical.
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A Case Report on Successful Third Challenge to the Pemetrexed-based Regimen for Advanced Non-small Cell Lung Cancer / 中国肺癌杂志

Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancer, with a 5-year survival rate of less than 15%-19%, and more than 80% of the patients with lung cancer have progressed to advanced stage (Stage IIIb-IV) when they are clearly diagnosed. The comprehensive treatment mainly based on chemotherapy as the primary form is now considered as the major therapy method for advanced NSCLC without actionable driver gene mutations. Pemetrexed plus platinum doublet as well as single-agent pemetrexed are respectively the first-line major regimens recommended by guidelines and the second-line optional regimens. Yet the third-line treatment or beyond in advanced NSCLC is not evidence-based but conducted based on patients' previous medications, which is one of the most commonly used clinical methods. As pemetrexed is a multi-target chemotherapy drug with high efficiency but low toxicity, pemetrexed re-challenge strategy in advanced NSCLC is also a reasonable choice. We report one effective individual case that adopted pemetrexed re-challenge strategy in advanced NSCLC for three times, and at the same time conduct the relevant literature review.