• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.3839-3841
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• 2015

Background: This pooled analysis was conducted to evaluate the efficacy and safety of pemetrexed based chemotherapy in treating patients with metastatic bladder cancer as salvage chemotherapy. Methods: Clinical studies evaluating the efficacy and safety of pemetrexed based regimens on response and safety for patients with bladder cancer were identified by using a predefined search strategy. Pooled response rate (RR) of treatment were calculated. Results: In pemetrexed based regimens, 3 clinical studies which including 105 patients with advanced transitional cell cancer of the urothelium were considered eligible for inclusion. Pooled analysis suggested that, in all patients, pooled RR was 26.7% (28/105) for pemetrexed based regimens. Major adverse effects were neutropenia, anorexia, fatigue, and anemia in pemetrexed based treatment. Two treatment related deaths occurred with pemetrexed based treatment. Conclusion: This pooled analysis suggests that pemetrexed based regimens are associated with mild activity and good tolerability in treating patients with metastatic bladder cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권11호
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• pp.4567-4570
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• 2014

Background: This systemic analysis was conducted to evaluate the efficacy and safety of pemetrexed based chemotherapy in treating patients with metastatic breast cancer as first or second line chemotherapy. Methods: Clinical studies evaluating the efficacy and safety of pemetrexed based regimens on response and safety for patients with breast cancer were identified using a predefined search strategy. Pooled response rate (RR) of treatment were calculated. Results: In first line pemetrexed based regimens, 10 clinical studies which including 513 patients with advanced breast cancer were considered eligible for inclusion. For second line pemetrexed based chemotherapy, 5 clinical studies which including 281 patients with advanced breast cancer were considered eligible. Systemic analysis suggested that, in all patients, pooled RR was 32.6% (167/513) in pemetrexed based first line regimens, and 13.9 % (39/281) in pemetrexed based second line regimens. Major adverse effects were neutropenia, leukopenia, fatigue, and anemia in pemetrexed based first line treatment; and lymphopenia, neutropenia, leukopenia, as well as anemia in second line chemotherapy. One treatment related death occurred with pemetrexed based second line treatment. Conclusion: This systemic analysis suggests that pemetrexed based first line regimens are associated with a reasonable response rate and acceptable toxicity, however with low response rate for treating patients with metastatic breast cancer when is used in the second line.

• 생명과학회지
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• 제20권1호
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• pp.103-112
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• 2010

페메트렉시드(pemetrexed, $alimta^{(R)}$)는 중피종(mesothelioma)과 비소세포폐암 (non-small cell lung cancer)을 비롯한 다양한 암종에서 엽산(folate) 대사과정에 관여하는 대사물질의 활성을 억제하여 항암효능을 나타낸다. 다중표적 항암제 (multitargeted antifolate)인 pemetrexed는 엽산의 세포내 주요 이동통로인 reduced folate carrier(RFC)를 통해 세포 내로 유입된 후 folylpolyglutamate synthetase (FPGS)에 의해 폴리글루타민산염(polyglutamate) 유도체로 활성되고 thymidylate synthase (TS)와 dihydrofolate reductase (DHFR)를 표적하는 것으로 알려져 있다. 조직형이 서로 다른 비소세포폐암 세포주를 선정하여 pemetrexed의 대사과정에 관여하는 유전자들의 단일염기서열 다형성을 조사하고, mRNA와 단백질의 발현 정도를 비교하여 pemetrexed의 세포독성 효과와의 상관성을 분석하였다. 4개의 비소세포폐암 세포주인 A549, PC14, HCC-1588과 H226에서 RFC, FPGS, TS와 DHFR의 유전형을 조사하였다. Pemetrexed의 약물의 감수성을 알아보기 위해 real-time PCR과 Western blot 방법으로 mRNA 발현과 단백질 발현 정도를 비교하였고, SRB 법으로 약물에 대한 세포독성 효과를 측정했다. PC14 세포주와 H226 세포주에서는 약물처리 전 RFC와 FPGS의 mRNA 발현이 높은 것으로 나타났고, $IC_{50}$값이 각각 $0.08{\pm}0.01\;uM$과 $0.07{\pm}0.01\;uM$로 pemetrexed에 대한 감수성이 높은 것을 알 수 있었다. A549 세포주에서 TS의 유전형이 2R/2R일 때 mRNA발현이 증가하고 pemetrexed의 약물 저항성과 관련이 있었다. 반면, TS의 유전형이 3R/3R로 나타난 H226에서는 mRNA 발현이 낮은 것을 알 수 있었지만 pemetrexed의 높은 감수성과 관련이 있었다. 세포주 모두에서 pemetrexed 약물처리 후 DHFR의 mRNA 발현은 약물처리 전보다 낮아지는 경향을 보였지만 단백질 발현은 오히려 증가하는 상반된 결과를 보였다. 또한 DHFR 프로모터에 위치한 -1726C>T, -1188A>C SNP는 서로 연쇄 불평형 상태(linkage disequilibrium, LD)에 있었다. 연구결과에서 pemetrexed의 세포독성 효과는 약물 대사과정에 관여하는 여러 분자들의 유전형과 발현 정도에 의해 결정되는 것을 알 수 있었고, 다양한 분석결과를 토대로 항암효능을 평가하는 것이 필요하다고 생각된다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권11호
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• pp.4791-4795
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• 2015

Purpose: This study was conducted to observe the efficacy and safety of pemetrexed based chemotherapy in treating patients with locally advanced or metastatic cancers as first-line, second-line or third-line therapy. Materials and Methods: From May 2011 to January 2015, we recruited 29 patients with advanced breast cancer, 19 patients with advanced ovary cancer, 17 patients with advanced esophageal cancer,5 patients with advanced gallbladder cancer,5 patients with advanced cervical cancer and 1 patient with advanced tongue cancer in Jiangsu Cancer Hospital and Research Institute.All of them were pathologically confirmed and treated with pemetrexed based chemotherapy. After two cycles of treatment,efficacy and safety can be evaluated. Results: For pemetrexed based regimens,including 76 patients with 6 kinds of advanced cancer were considered eligible for inclusion. Complete remission represents CR, partial remission represents PR, stable disease represents SD, progressive disease represents PD. Among 29 patients with advanced breast cancer, 4 patients chose pemetrexed based regimens as second-line treatment,1 of them was PR,the other 3 got SD. The last 25 patients made use of this chemotherapy as third-line treatment, except one patient could not be assessed, 2 of them got PR,6 of them got SD,the remaining 16 of them finally were PD.19 patients with advanced ovary cancer,5 patients used this regimens as second-line treatment, 3 of them got PD,the remaining patients got SD, respectively. The last 14 patients made use of pemetrexed based regimens as third-line treatment,. RR (CR+PR) was 28.5%. Among 17 patients with advanced esophageal cancer, 2 patients made use of pemetrexed based regimens as first-line treatment,both of them got PR.4 of them used this chemotherapy as second-line regimen, except 2 patients could not be assessed,the remaining 2 was PD at last. The last 11 patients was third-line users, RR (CR+PR) was 18.2%. Among 5 patients with advanced gallbladder cancer, pemetrexed based regimens was used in 1 patient as first-line treatment and 1 patient as second-line treatment. The curative effect was SD and PD, respectively. 3 patients accepted pemetrexed based regimens as third-line treatment, 2 of them got PD as results and another was SD. Among 5 patients with advanced cervical cancer, just 1 patient adopted pemetrexed based regimens as first-line treatment, whose curative effect was PR.2 patients chose this chemotherapy regimens as second-line treatment. Both of them got PD as their consequence. The last 2 patients made use of the regimens as third-line treatment, the effect of them was PD and SD, respectively. The one who with advanced tongue cancer, pemetrexed based regimens was used as second-line treatment, and the consequence was PD. About 71.1% patients experienced bone marrow suppression. Among them, 5 patients reached 4 grade. Other toxicity of pemetrexed were neurotoxicity, fatigue, diarrhea, dysphagia and vomiting. No treatment related death occurred with pemetrexed-based treatment. Conclusions: Pemetrexed based chemotherapy has considerable effect in patients with advanced cancers such as breast cancer,esophageal cancer and ovary cancer. More randomly clinical trials are needed to verify the results.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7137-7139
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• 2014

Background: This systemic analysis was conducted to evaluate the efficacy and safety of pemetrexed based chemotherapy in treating patients with metastatic gastric cancer (MGC) as a salvage chemotherapy. Methods: Clinical studies evaluating the efficacy and safety of pemetrexed based regimens on response and safety for patients with gastric cancer were identified by using a predefined search strategy. Pooled response rates (RRs) of treatment were calculated. Results: In pemetrexed based regimens, 4 clinical studies including 171 patients with advanced gastric cancer were considered eligible for inclusion. Systemic analysis suggested that, in all patients, pooled RR was 25.1% (43/171) in pemetrexed based regimens. Major adverse effects were neutropenia, anorexia, fatigue, and anemia. No treatment related death occurred in pemetrexed based treatment. Conclusion: This systemic analysis suggests that pemetrexed based regimens are associated with mild activity with good tolerability in treating patients with MGC.

• Asian Pacific Journal of Cancer Prevention
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• 제16권4호
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• pp.1507-1513
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• 2015

Pemetrexed is an antifolate agent which has been used for treating malignant pleural mesothelioma and non small lung cancer in the clinic as a chemotherapeutic agent. In this study, pemetrexed inhibited cell growth and induced G1 phase arrest in the A549 cell line. To explore the molecular mechanisms of pemetrexed involved in cell growth, we used a two-dimensional polyacrylamide gel electrophoresis (2-DE) proteomics approach to analyze proteins changed in A549 cells treated with pemetrexed. As a result, twenty differentially expressed proteins were identified by ESI-Q-TOF MS/MS analysis in A549 cells incubated with pemetrexed compared with non-treated A549 cells. Three key proteins (GAPDH, HSPB1 and EIF4E) changed in pemetrexed treated A549 cells were validated by Western blotting. Accumulation of GAPDH and decrease of HSPB1 and EIF4E which induce apoptosis through inhibiting phosphorylation of Akt were noted. Expression of p-Akt in A549 cells treated with pemetrexed was reduced. Thus, pemetrexed induced apoptosis in A549 cells through inhibiting the Akt pathway.

• Tuberculosis and Respiratory Diseases
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• 제81권2호
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• pp.148-155
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• 2018

Background: Although targeted therapy and immuno-oncology have shifted the treatment paradigm for lung cancer, platinum-based combination is still the standard of care for advanced non-small cell lung cancer (NSCLC). Pemetrexed continuation maintenance therapy has been approved and increasingly used for patients with nonsquamous NSCLC. However, the efficacy of this strategy has not been proven in patients without driving mutations. The objective of this study was to compare the clinical benefit of pemetrexed continuation maintenance to conventional platinum-based doublet in epidermal growth factor receptor (EGFR)-negative lung adenocarcinoma. Methods: A total of 114 patients with EGFR-negative lung adenocarcinoma who were treated with platinum doublet were retrospectively enrolled. We compared the survival rates between patients received pemetrexed maintenance after four-cycled pemetrexed/cisplatin and those received at least four-cycled platinum doublet without maintenance chemotherapy as a first-line treatment. Results: Forty-one patients received pemetrexed maintenance and 73 received conventional platinum doublet. Median progression-free survival (PFS), which was defined as the time from the day of response evaluation after four cycles of chemotherapy to disease progression or death, was significantly higher in the pemetrexed maintenance group compared to conventional group (5.8 months vs. 2.2 months, p<0.001). Median overall survival showed an increasing trend in the pemetrexed maintenance group (22.3 months vs. 16.1 months, p=0.098). Multivariate analyses showed that pemetrexed maintenance chemotherapy was associated with better PFS (hazard ratio, 0.73; 95% confidence interval, 0.15-0.87). Conclusion: Compared to conventional platinum-based chemotherapy, premetrexed continuation maintenance treatment is associated with better clinical outcome for the patients with EGFR wild-type lung adenocarcinoma.

• Asian Pacific Journal of Cancer Prevention
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• 제15권8호
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• pp.3447-3450
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• 2014

Objective: To observe the clinical efficacy of bevacizumab concomitant with pemetrexed in patients with advanced non-small cell lung cancer (NSCLC). Materials and Methods: A total of 72 patients were randomly divided into a combination group (pemetrexed+bevacizumab, n=36) and a pemetrexed group (n=36) and assessed for disease control (CR+PR+SD) after 4-cycles of first-line GP chemotherapy (gemcitabine+cisplatin). Clinical efficacy, progression-free survival time (PFS), overall survival time (OS), overall response rate (ORR), disease control rate (DCR) and rate of adverse responses between two groups were observed and compared. Results: ORR and DCR were 27.8% and 83.4% in combination group, and 16.7% and 69.5% in the pemetrexed group, respectively, but there were no significant differences (P>0.05). PFS in combination group and pemetrexed group were 4.6 months and 3.9 months respectively (P=0.09), whereas OS in the combination group was 14 months, evidently higher than in the pemetrexed group (11 months, P=0.004). Adverse responses in both groups included high blood pressure, bleeding, thrombocytopenia, anemia, elevated transaminase, diarrhea, vomiting and proteinuria, but there were no significant differences (P>0.05). Conclusions: Bevacizumab concomitant with pemetrexed has better clinical efficacy and safety, giving rise to prolonged survival time in patients with advanced NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• 제15권19호
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• pp.8475-8478
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• 2014

Purpose: This systematic analysis was conducted to evaluate the efficacy and safety of pemetrexed-based chemoradiotherapy in treating patients with locally advanced or metastatic esophageal cancer. Methods: Clinical studies evaluating the efficacy and safety of pemetrexed based regimens on response and safety for relevant patients were identified using a predefined search strategy. Pooled response rates (RRs) were calculated. Results: For pemetrexed-based regimens, 4 clinical studies including 47 patients with locally advanced or metastatic esophageal cancer were considered eligible for inclusion. Systematic analysis showed that, in all patients, the pooled RR was 51% (24/47). Major adverse effects of grade III/IV were esophagitis, neutropenia, thrombocytopenia, anemia anorexia, fatigue, diarrhea, dysphagia and vomiting. No treatment related death occurred with pemetrexed-based treatment. Conclusion: This systematic analysis suggests that pemetrexed based radiotherapy is associated with reasonable activity and good tolerability in treating patients with locally advanced or metastatic esophageal cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권19호
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• pp.8391-8394
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• 2014

Purpose: This systematic analysis was conducted to evaluate the efficacy and safety of pemetrexed based salvage chemotherapy for treatment of patients with metastatic colorectal cancer. Methods: Clinical studies evaluating the efficacy and safety of pemetrexed based regimens on response and safety for patients with colorectal cancer were identified using a predefined search strategy. Pooled response rates (RRs) were calculated. Results: For pemetrexed based regimens, 4 clinical studies including 201 patients with advanced colorectal cancer were considered eligible for inclusion. The analysis suggested that, in all patients, pooled RR was 20.4% (41/201). Major adverse effects were neutropenia, anorexia, fatigue, and anemia. No treatment related death occurred with pemetrexed based treatment. Conclusion: This systematic analysis suggests that pemetrexed based regimens are associated with mild activity with good tolerability in treating patients with metastatic colorectal cancer.