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Malignant Mesothelioma. Mesothelioma is an insidious neoplasm arising from the mesothelial surfaces of the pleural and peritoneal cavities, the tunica vaginalis, or the pericardium . Mesothelioma Causes. The vast majority of mesothelioma cases are attributed to asbestos exposure.
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Malignant Mesothelioma Mesothelioma is an insidious neoplasm arising from the mesothelial surfaces of the pleural and peritoneal cavities, the tunica vaginalis, or the pericardium.
Mesothelioma Causes • The vast majority of mesothelioma cases are attributed to asbestos exposure. • Less common causes of mesothelioma include: • Radiation therapy • Erionite fibers (genetic susceptibility) • Collapsotherapy (the induction of artificial pneumothorax or pneumoperitoneum for treatment of tuberculosis) • The DNA tumor virus SV40
Mesothelioma Industries with High Incidence of Mesothelioma • Construction (carpenters, plumbers, electricians, insulators) • Ship and boat building • Manufacture of cement products • Manufacture of non-metallic mineral products (including asbestos) • Glass products manufacturing • Generation of electricity • Brick and ceramic products manufacturing • McDonald etal,2001
Observed (to 1989) and predicted (1990-2029) annual no. of pleural cancer deaths in men in Western Europe. From: J. Peto et al. Br. J. Cancer 79: 666-672 (1999)
Absolute frequency of MM, recorded at NCI, Cairo and Abbassia chest hospital Relative frequency of MPM, NCI hospital-based registry Alyeldin etal,MOG ,Alex,2004
Lancet vol 366, July 30 ,2005Robinson etalMalignant mesotheliomaNo chemotherapy regimen for mesothelioma has proven curative , but several regimes are valuable for palliation. These treatments not only decrease tumor burden but also improve symptoms such as pain, breathlessness and chest wall masses.Untill 5 years ago, comprehensive reviews of chemotherapy and mesothelioma were unable to recommend any particular therapy as a standard of care because of the low RR. Two therapeutic regimens have since proven to be of value.
In patients with good PS, we consider the standard of care for 1st line palliative chemotherapy to be Pemetrexed + Cisplatin. There is no 2ndline chemotherapy that could be considered as standard of care at present but the most commonly used regimen is Gemcitabine and cisplatin.Robinson etal,2005
ALIMTA Reduced polyglutamates Folate Carrier Mechanism of Action of ALIMTA TS DHFR FPGS ALIMTA GARFT AICARFT Outer Membrane Cell Membrane Inner Membrane C-1 THF Synthetase
Cisplatin+/- PemetrexedVogelzang etal,JCO 21: 2636, 2003 D1 Q 21 days: • Cisplatin 75 mg/m2 +/- • Pemetrexed 500mg/m2 Dexametazone 4mg POBID Eligibility: measurable pleural mesothelioma, PS ≥70, adequate organ function, Creat. Clear. ≥45ml/mn, no prior chemo therapy. Total number of cases= 456 Number for final analysis = 448 Phase III trial
Protocol Overview H3E-US-JMFE Open-Label Study of ALIMTA (pemetrexed) alone or in Combination with Cisplatin for Patients with Malignant Mesothelioma NCI, CAIRO
Primary Objective • To provide for the treatment of patients with malignant mesothelioma. Patient access to ALIMTA will be provided under this protocol prior to and during its review by Regulatory Agencies for commercial release. • Collection of further basic safety data • Determination of the best overall tumor response Secondary Objectives
NCI-CTC Toxicities (N=34) Can list Grade 1 - 4 if known or list as 3/4
FDA Approves Alimta-Cisplatin Combination for Treatment of Asbestos-Related Cancer February 05, 2004
Conclusions Pemetrexed with or without cisplatin proved to be safe and effective in the treatment of advanced malignant mesothelioma. Pemetrexed/Cisplatinum is now the standard therapy in malignant mesothelioma against which other doublets will be compared Trials are now investigating the role of Pemetrexed/Cisplatinum prior to surgical resection
A phase II feasibility trial of induction chemotherapy followed by extrapleural pneumonectomy and postoperative radiotherapy in patients with malignant pleural mesothelioma EORTC Protocol 08031 Study coordinator: Paul E. Van Schil
Serum mesothelin-related protein (SMRP) formesothelioma diagnosisUntil recently, no reliable serum marker of mesothelioma had been identified. SMRP is the circulating product of mesothelin, a surface protein thought to be important in mesothelial cell adhesion and possibly signalling; it is possibly the protein product of an alternatively spliced variant of mesothelin mRNA. In astudy of 44 mesothelioma patients, 84% had elevated concentrations of SMRP compared with fewer than 2% of patients with other pleural or pulmonary inflammatory or malignant diseases . Thus SMRP had a sensitivity of 84% and specificity approaching 100% compared with other lung tumours or pleural diseases, and a specificity over 80% compared with other people who had been exposed to asbestos. SMRP concentrations parallel disease progression and regression, and, importantly, are elevated in more than 60% of mesothelioma patients at diagnosis. SMRP will probably be used as an adjunct for mesothelioma diagnosis. Robinson etal,2005
A M M + + Pretreatment After 4 cycles
A M M Pretreatment After 4 cycles
AMM Pretreatment
AMM After 4 cycles
F M E + + Pretreatment After 2 cycles
F M E + + After 2 cycles Pretreatment
M A + Pretreatment
M A After 4 cycles
M N + + Pretreatment
M N After 2 cycles
M N After 1 year
M N Prettt After 2 cycles + + After 1 year
Pemetrexed-Cisplatin :A New Standard Therapy for Advanced Malignant Mesothelioma Rabab Gaafar,MD Professor Medical OncologyNational Cancer Institute, Cairo University Damascus, June 1-3, 2005