The latest treatment of malignant pleural mesothelioma Progress
The latest treatment of malignant pleural mesothelioma Progress
Malignant pleural mesothelioma has been reported median survival of = 1 year, 5-year survival rate of = 1%, so that over the years the treatment of malignant pleural mesothelioma hold a nothingness attitude (Ceresoli GL, Locati LD, Ferreri AJ , et al.2001). However, with the exception of their knowledge about the molecular, biological characteristics of the disease is gradually being understood. Along with molecular biology, immunology, development, and the development of clinical practice itself, treatment of the disease has a new hope. Targeted therapy: to bring hope
Malignant pleural mesothelioma is not sensitive to chemotherapy, targeted therapy to provide adequate space for the development. Being studied anti-angiogenic drugs, including bevacizumab, thalidomide, BAY43-9006 and PTK787, other specific blocking drugs, including mesothelioma pathway histone deacetylase inhibitor (suberoylanilide hydroxamic acid) , proteosome inhibitor bortezomib (bortezomib), labeled toxin monoclonal anti-mesothelin antibody, Vorinostat, everolimus (everolimus, RAD001) and temsirolimus and other drugs are already in clinical trials (Pasello G and Favaretto A 2009).
Epidermal growth factor receptor (EGFR) expression in mesothelioma high, and in vitro experiments confirmed that EGFR tyrosine kinase inhibitor gefitinib inhibited mesothelioma, but ? clinical trial found that the efficacy of gefitinib little . Partly due to mutations in the EGFR gene mesothelioma common. Similarly, preclinical data suggest that platelet-derived growth factor (PDGF) in pleural mesothelioma has an important role, but imatinib, PDGF receptor tyrosine kinase selective inhibitor in Phase ? clinical trials failed. There Nicole vitro evidence for enhanced Mingyi Ma role gemcitabine (Bertino P, Piccardi F, Porta C, et al.2008), clinical trials have yet to be confirmed.
Vascular endothelial growth factor (VEGF) signaling pathway in mesothelioma biological functions play an important role. High serum VEGF levels indicates a poor prognosis, short survival. SU5416, Vatalanib (vatalanib, PTK787/ZK 222584), thalidomide and sorafenib Phase ? clinical trials only a slight effect. Vatalanib is PDGFR-b and all the VEGFR tyrosine kinase inhibitor, in a phase ? CALGB trial (Pasello G and Favaretto A.2009), the effective rate of 11%, stable disease rate was 66%. The median survival time was 10 months. Thalidomide Netherlands 40 patients ? clinical studies suggest that 27.5% of patients had stable disease for more than 6 months. On this basis, conduct clinical trials Phase ? NVALT 5, line pemetrexed chemotherapy be thalidomide maintenance treatment. CALGB (Janne PA, Wang XF, Krug LM, et al.2007) of sorafenib, VEGFR-2, PDGFR-b and raf kinase inhibitor used untreated or previously treated patients, patients with previously untreated The median survival time was 5.2 months, and previously treated patients was 14.3 months. A Phase I trial will sorafenib with doxorubicin combined with the treatment of refractory tumors, there is one case of malignant pleural mesothelioma patients get partial remission, and continued application of 39.7 weeks. Ongoing sunitinib (sunitinib) second-line treatment of malignant pleural mesothelioma Phase ? trial prompts (Pasello G and Favaretto A.2009), conventional CT scans an average of 15% efficiency, PET-CT evaluation, there 30% efficient.
A randomized double-blind Phase ? clinical study (Karrison T, Kindler HL, Gandara DR, et al.2007), the anti-VEGF monoclonal antibody bevacizumab in combination with gemcitabine and cisplatin (GC). However, preliminary results suggest that, GC bevacizumab after progression-free survival, overall survival, efficient and toxic reactions showed no significant differences. Bevacizumab progression-free survival was 6.9 months in the placebo group, 6.0 months (HR 0.93, P = 0.88), median survival was 15.6 months and 14.7 months (P = 0.91). Low blood levels of VEGF were progression-free survival and overall survival are extended.
Src is highly expressed in mesothelioma and activated. Src kinase activity associated with mesothelioma staging may promote tumor invasion and metastasis spread. Dasatinib (Dasatinib / Sprycel), Src family kinases strong inhibitor, in preclinical models of mesothelioma inhibit migration and invasion (Tsao AS, He D, Saigal B, et al.2007). CALGB is currently undergoing clinical trials for previously treated patients.
Including histone deacetylase inhibitors (suberoylanilide hydroxamic acid, SAHA), oral histone deacetylase inhibitor ? and ? in vitro experiments confirmed that inhibit the growth of mesothelioma. SAHA inhibition of thymidylate synthase gene, which is the role of pemetrexed targets. ? clinical trials (Pasello G and Favaretto A.2009), 13 patients except one are those who progress after first-line chemotherapy. There are two cases in which achieved partial remission (PR). Toxicities were tolerable. Which is currently undergoing a randomized, double-blind, placebo-controlled international Phase ? clinical trials second-line treatment of malignant pleural mesothelioma, to be enrolled in 660 cases, the primary endpoint was overall survival (ClinicalTrials.gov Identifier: NCT00128102), which Results worth the wait.
New therapy: to be verified
Animal studies and clinical trials are prompted for immunotherapy of malignant pleural mesothelioma sensitive. Interferon-a, interleukin-2 and pleural tumor granulocytes - megakaryocyte colony stimulating factor, the trial showed a certain effect on the tumor. However, there is no strong evidence to ensure widespread use of these drugs.
Apoptosis-inducing drugs (such as gemcitabine) and the antigen-presenting cells (such as anti-CD40 antibody molecule) combined immunotherapy, both in animal models synergy can most advanced long-term cure of malignant pleural mesothelioma. Chemotherapy in mesothelioma cells with TRAIL agonists have a synergistic effect (Abayasiriwardana KS, Barbone D, Kim KU, et al.2007).
Gene therapy of cancer patients will usually use genetically engineered viruses. A small-scale trial (Kindler HL.2008), 6 ? previous treatment-resistant malignant mesothelioma patients receiving intratumoral injection of interleukin-2 transgenic vaccine vector in order to regulate the immune response. The treatment induced lymphocyte infiltration as well as very low levels of persistent transgene expression, but no significant tumor remission. Suicide gene therapy, which encodes the viral thymidine kinase into viral vectors, ganciclovir by the toxic metabolites of drugs into leaving the cell is sensitive. For patients with malignant mesothelioma have a certain effect.
Photodynamic therapy is a light sensitive drugs acting on the production of ROS induced cell necrosis. The treatment time consuming, can be reached in malignant mesothelioma tumor reduction purposes. Combined with the EPP, you can make local disease control rate 50%, but the treatment toxicity limits its promotion, has yet to see significant long-term effects (Kindler HL. 2008).
Palliative symptomatic treatment: improvement of symptoms
Pleural effusion can be repeated all the leads, if necessary suction. If the chest is still not relieve shortness of breath after pumping fluid may cause pulmonary embolism or cancer should consider lymphangitis. Early application of effective control of pleurodesis pleural effusion for improving symptoms and preventing the occurrence of trapping the lung (trapped lung) is very important. After repeated thoracentesis, pleural effusion may be wrapped, it is possible to continue the pleural drainage increases the chances of infection. If the diagnosis is clear, intercostal drainage from the chest wall to be small mouth chemicals pleurodesis. Curing agent is desirable sterile talc, the success rate of 70% to 96%. The amount of talc particles to be suitable to prevent the occurrence of a rare adult respiratory distress syndrome. If there is a trapping lung or pleura fixation failure, consider the abdominal shunt. More than 90% of the patients symptoms can be improved, but complications (including shunt blockage and infection) rate was 15%, so this method is not gradually (Heffner JE and Klein JS.2008).
Recently a portable chest drainage system is being applied. Through long-term catheter drainage and vacuum bottles, patients at home to control pleural effusion. Such trapping surgical intervention can be avoided in patients with lung and relieve shortness of breath.
Patients with malignant pleural mesothelioma There are many types of pain. Tumor invasion of the chest wall caused by somatic pain. Intercostal nerve or vertebral invasion induced neuropathic pain. After widespread organ involvement visceral pain, pain is very difficult. The role of opioids in the duration of analgesia and side effects should be enough. Opioids based on the non-steroidal anti-inflammatory drugs are usually effective for somatic pain. Neuropathic pain be added with anticonvulsants, such as carbamazepine or valproate. Some patients need surgery painkillers such as intrathecal analgesic drugs or nerve block. Surrounding the lung due to pleural effusion and tumor more common causes shortness of breath, when the reversible causes of anemia, such as pleural effusion and get treatment, opioid helps relieve shortness of breath (Heffner JE and Klein JS. 2008).
Malignant pleural mesothelioma is not sensitive to chemotherapy, targeted therapy to provide adequate space for the development of various targeted drugs have moved into clinical trials. (Refining)
Radiotherapy combined with cetuximab in patients with locally advanced head and neck cancer: Five-year survival and efficacy analysis
Bonner JA, Harari PM, Giralt J, et al.
N Engl J Med 2006 reported an initial radiotherapy treatment with cetuximab in locally advanced head and neck squamous cell carcinoma (LASCCHN) ? randomized trial showed that patients with three-year overall survival rate increased. The trial Lancet recently published a 5-year survival data, and rashes caused by cetuximab correlation with survival analysis.
Into the group by oropharyngeal, glossopharyngeal and throat patients with measurable disease LASCCHN, 1:1 randomized, giving head and neck radiotherapy alone integrated 6 ~ 7wk (n = 213) or radiotherapy plus cetuximab (loading dose: 400 mg · m-2 · wk-1, maintenance dose: 250 mg · m-2 · wk-1 × 7, n = 211). The non-blinded trial, the primary end point for the local regional control rate, the secondary outcome measure was survival. Analysis was by intention to treat. After treatment, patients were once every four months physical examination and imaging studies, two years after every six months.
Follow-up period, all patients were alive. Cetuximab plus radiotherapy with radiotherapy alone group, the median overall survival was 49.0 months (95% CI 32.8 - 69.5) and 29.3 months (95% CI of 20.6 ~ 41.4) (HR 0.73,95% CI = 0.56 ~ 0.95, P = 0.018); 5-year overall survival rates were 45.6% and 36.4% respectively. In addition, due to cetuximab therapy in patients with no or grade ? rash compared ? degree and above occurrence of acne rash of patients significantly improved overall survival (HR 0.49,95% CI of 0.34 ~ 0.72, P = 0.002 ).
Visible, and only accepts radiotherapy alone compared cetuximab plus radiotherapy can significantly improve LASCCHN 5-year survival of patients, but also affirmed the cetuximab plus radiotherapy may be used as such an important treatment option for patients . With cetuximab caused no rash or grade ? compared with patients, the occurrence of grade ? and better survival rates than patients with rash.
Malignant pleural mesothelioma has been reported median survival of = 1 year, 5-year survival rate of = 1%, so that over the years the treatment of malignant pleural mesothelioma hold a nothingness attitude (Ceresoli GL, Locati LD, Ferreri AJ , et al.2001). However, with the exception of their knowledge about the molecular, biological characteristics of the disease is gradually being understood. Along with molecular biology, immunology, development, and the development of clinical practice itself, treatment of the disease has a new hope. Targeted therapy: to bring hope
Malignant pleural mesothelioma is not sensitive to chemotherapy, targeted therapy to provide adequate space for the development. Being studied anti-angiogenic drugs, including bevacizumab, thalidomide, BAY43-9006 and PTK787, other specific blocking drugs, including mesothelioma pathway histone deacetylase inhibitor (suberoylanilide hydroxamic acid) , proteosome inhibitor bortezomib (bortezomib), labeled toxin monoclonal anti-mesothelin antibody, Vorinostat, everolimus (everolimus, RAD001) and temsirolimus and other drugs are already in clinical trials (Pasello G and Favaretto A 2009).
Epidermal growth factor receptor (EGFR) expression in mesothelioma high, and in vitro experiments confirmed that EGFR tyrosine kinase inhibitor gefitinib inhibited mesothelioma, but ? clinical trial found that the efficacy of gefitinib little . Partly due to mutations in the EGFR gene mesothelioma common. Similarly, preclinical data suggest that platelet-derived growth factor (PDGF) in pleural mesothelioma has an important role, but imatinib, PDGF receptor tyrosine kinase selective inhibitor in Phase ? clinical trials failed. There Nicole vitro evidence for enhanced Mingyi Ma role gemcitabine (Bertino P, Piccardi F, Porta C, et al.2008), clinical trials have yet to be confirmed.
Vascular endothelial growth factor (VEGF) signaling pathway in mesothelioma biological functions play an important role. High serum VEGF levels indicates a poor prognosis, short survival. SU5416, Vatalanib (vatalanib, PTK787/ZK 222584), thalidomide and sorafenib Phase ? clinical trials only a slight effect. Vatalanib is PDGFR-b and all the VEGFR tyrosine kinase inhibitor, in a phase ? CALGB trial (Pasello G and Favaretto A.2009), the effective rate of 11%, stable disease rate was 66%. The median survival time was 10 months. Thalidomide Netherlands 40 patients ? clinical studies suggest that 27.5% of patients had stable disease for more than 6 months. On this basis, conduct clinical trials Phase ? NVALT 5, line pemetrexed chemotherapy be thalidomide maintenance treatment. CALGB (Janne PA, Wang XF, Krug LM, et al.2007) of sorafenib, VEGFR-2, PDGFR-b and raf kinase inhibitor used untreated or previously treated patients, patients with previously untreated The median survival time was 5.2 months, and previously treated patients was 14.3 months. A Phase I trial will sorafenib with doxorubicin combined with the treatment of refractory tumors, there is one case of malignant pleural mesothelioma patients get partial remission, and continued application of 39.7 weeks. Ongoing sunitinib (sunitinib) second-line treatment of malignant pleural mesothelioma Phase ? trial prompts (Pasello G and Favaretto A.2009), conventional CT scans an average of 15% efficiency, PET-CT evaluation, there 30% efficient.
A randomized double-blind Phase ? clinical study (Karrison T, Kindler HL, Gandara DR, et al.2007), the anti-VEGF monoclonal antibody bevacizumab in combination with gemcitabine and cisplatin (GC). However, preliminary results suggest that, GC bevacizumab after progression-free survival, overall survival, efficient and toxic reactions showed no significant differences. Bevacizumab progression-free survival was 6.9 months in the placebo group, 6.0 months (HR 0.93, P = 0.88), median survival was 15.6 months and 14.7 months (P = 0.91). Low blood levels of VEGF were progression-free survival and overall survival are extended.
Src is highly expressed in mesothelioma and activated. Src kinase activity associated with mesothelioma staging may promote tumor invasion and metastasis spread. Dasatinib (Dasatinib / Sprycel), Src family kinases strong inhibitor, in preclinical models of mesothelioma inhibit migration and invasion (Tsao AS, He D, Saigal B, et al.2007). CALGB is currently undergoing clinical trials for previously treated patients.
Including histone deacetylase inhibitors (suberoylanilide hydroxamic acid, SAHA), oral histone deacetylase inhibitor ? and ? in vitro experiments confirmed that inhibit the growth of mesothelioma. SAHA inhibition of thymidylate synthase gene, which is the role of pemetrexed targets. ? clinical trials (Pasello G and Favaretto A.2009), 13 patients except one are those who progress after first-line chemotherapy. There are two cases in which achieved partial remission (PR). Toxicities were tolerable. Which is currently undergoing a randomized, double-blind, placebo-controlled international Phase ? clinical trials second-line treatment of malignant pleural mesothelioma, to be enrolled in 660 cases, the primary endpoint was overall survival (ClinicalTrials.gov Identifier: NCT00128102), which Results worth the wait.
New therapy: to be verified
Animal studies and clinical trials are prompted for immunotherapy of malignant pleural mesothelioma sensitive. Interferon-a, interleukin-2 and pleural tumor granulocytes - megakaryocyte colony stimulating factor, the trial showed a certain effect on the tumor. However, there is no strong evidence to ensure widespread use of these drugs.
Apoptosis-inducing drugs (such as gemcitabine) and the antigen-presenting cells (such as anti-CD40 antibody molecule) combined immunotherapy, both in animal models synergy can most advanced long-term cure of malignant pleural mesothelioma. Chemotherapy in mesothelioma cells with TRAIL agonists have a synergistic effect (Abayasiriwardana KS, Barbone D, Kim KU, et al.2007).
Gene therapy of cancer patients will usually use genetically engineered viruses. A small-scale trial (Kindler HL.2008), 6 ? previous treatment-resistant malignant mesothelioma patients receiving intratumoral injection of interleukin-2 transgenic vaccine vector in order to regulate the immune response. The treatment induced lymphocyte infiltration as well as very low levels of persistent transgene expression, but no significant tumor remission. Suicide gene therapy, which encodes the viral thymidine kinase into viral vectors, ganciclovir by the toxic metabolites of drugs into leaving the cell is sensitive. For patients with malignant mesothelioma have a certain effect.
Photodynamic therapy is a light sensitive drugs acting on the production of ROS induced cell necrosis. The treatment time consuming, can be reached in malignant mesothelioma tumor reduction purposes. Combined with the EPP, you can make local disease control rate 50%, but the treatment toxicity limits its promotion, has yet to see significant long-term effects (Kindler HL. 2008).
Palliative symptomatic treatment: improvement of symptoms
Pleural effusion can be repeated all the leads, if necessary suction. If the chest is still not relieve shortness of breath after pumping fluid may cause pulmonary embolism or cancer should consider lymphangitis. Early application of effective control of pleurodesis pleural effusion for improving symptoms and preventing the occurrence of trapping the lung (trapped lung) is very important. After repeated thoracentesis, pleural effusion may be wrapped, it is possible to continue the pleural drainage increases the chances of infection. If the diagnosis is clear, intercostal drainage from the chest wall to be small mouth chemicals pleurodesis. Curing agent is desirable sterile talc, the success rate of 70% to 96%. The amount of talc particles to be suitable to prevent the occurrence of a rare adult respiratory distress syndrome. If there is a trapping lung or pleura fixation failure, consider the abdominal shunt. More than 90% of the patients symptoms can be improved, but complications (including shunt blockage and infection) rate was 15%, so this method is not gradually (Heffner JE and Klein JS.2008).
Recently a portable chest drainage system is being applied. Through long-term catheter drainage and vacuum bottles, patients at home to control pleural effusion. Such trapping surgical intervention can be avoided in patients with lung and relieve shortness of breath.
Patients with malignant pleural mesothelioma There are many types of pain. Tumor invasion of the chest wall caused by somatic pain. Intercostal nerve or vertebral invasion induced neuropathic pain. After widespread organ involvement visceral pain, pain is very difficult. The role of opioids in the duration of analgesia and side effects should be enough. Opioids based on the non-steroidal anti-inflammatory drugs are usually effective for somatic pain. Neuropathic pain be added with anticonvulsants, such as carbamazepine or valproate. Some patients need surgery painkillers such as intrathecal analgesic drugs or nerve block. Surrounding the lung due to pleural effusion and tumor more common causes shortness of breath, when the reversible causes of anemia, such as pleural effusion and get treatment, opioid helps relieve shortness of breath (Heffner JE and Klein JS. 2008).
Malignant pleural mesothelioma is not sensitive to chemotherapy, targeted therapy to provide adequate space for the development of various targeted drugs have moved into clinical trials. (Refining)
Radiotherapy combined with cetuximab in patients with locally advanced head and neck cancer: Five-year survival and efficacy analysis
Bonner JA, Harari PM, Giralt J, et al.
N Engl J Med 2006 reported an initial radiotherapy treatment with cetuximab in locally advanced head and neck squamous cell carcinoma (LASCCHN) ? randomized trial showed that patients with three-year overall survival rate increased. The trial Lancet recently published a 5-year survival data, and rashes caused by cetuximab correlation with survival analysis.
Into the group by oropharyngeal, glossopharyngeal and throat patients with measurable disease LASCCHN, 1:1 randomized, giving head and neck radiotherapy alone integrated 6 ~ 7wk (n = 213) or radiotherapy plus cetuximab (loading dose: 400 mg · m-2 · wk-1, maintenance dose: 250 mg · m-2 · wk-1 × 7, n = 211). The non-blinded trial, the primary end point for the local regional control rate, the secondary outcome measure was survival. Analysis was by intention to treat. After treatment, patients were once every four months physical examination and imaging studies, two years after every six months.
Follow-up period, all patients were alive. Cetuximab plus radiotherapy with radiotherapy alone group, the median overall survival was 49.0 months (95% CI 32.8 - 69.5) and 29.3 months (95% CI of 20.6 ~ 41.4) (HR 0.73,95% CI = 0.56 ~ 0.95, P = 0.018); 5-year overall survival rates were 45.6% and 36.4% respectively. In addition, due to cetuximab therapy in patients with no or grade ? rash compared ? degree and above occurrence of acne rash of patients significantly improved overall survival (HR 0.49,95% CI of 0.34 ~ 0.72, P = 0.002 ).
Visible, and only accepts radiotherapy alone compared cetuximab plus radiotherapy can significantly improve LASCCHN 5-year survival of patients, but also affirmed the cetuximab plus radiotherapy may be used as such an important treatment option for patients . With cetuximab caused no rash or grade ? compared with patients, the occurrence of grade ? and better survival rates than patients with rash.
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