Asian Cardiovasc Thorac Ann 2006 Jun; 14(3): e60-2 (Read article online)

Huwer H, Winning J, Isringhaus H, Kalweit G

Following right-sided pneumonectomy and hemidiaphragm resection in a 58-year-old man with epithelioid mesothelioma, acute respiratory insufficiency and life-threatening circulatory collapse developed after a forced Valsalva maneuver. Major pulmonary embolism was diagnosed on clinical grounds, however computed tomography revealed herniation of the liver into the right hemithorax.

J Comp Pathol 2006 May 16; (Read article online)

Bacci B, Morandi F, De Meo M, Marcato PS

In the cat only 10 cases of mesothelioma, mainly of the peritoneum, have been previously reported. This paper describes a further 10 cases, eight pleural and two peritoneal, in males and females aged 1-17 years. Histologically, five tumours were epithelial, three fibrosarcomatous and two biphasic. Immunohistochemical markers used in human pathology for the identification of mesotheliomas include vimentin, cytokeratin (CK) AE1/AE3, HBME-1, CK 5/6, calretinin, thrombomodulin, carcinoembryonic antigen (CEA), CD15, E-cadherin and desmin. All 10 feline mesotheliomas were positive for vimentin and CK AE1/AE3, six were positive for HBME-1, two for CK5/6, three for CEA and four for E-cadherin. All were negative for desmin and calretinin. Antibodies to thrombomodulin and CD15 failed to cross-react with feline tissues. Electron microscopy, performed in four cases, revealed microvillar structures, desmosomes and intracytoplasmic lumina, confirming its value as a diagnostic tool. The study showed that mesothelial marker antibodies commonly used in human patients can be used for the diagnosis of feline mesothelioma, preferably as a panel of antibodies rather than only one.

Med Lav 2005 Sep-Oct; 96(5): 426-31 (Read article online)

Lombardi S, Girelli R, Barbieri PG

BACKGROUND: In Italy there was a wide use of asbestos in various manufacturing sectors and for many different uses, some of which are still partly or completely unknown. A detailed reconstruction of the work histories of mesothelioma patients made it possible, in some cases, to identify ignored circumstances of asbestos exposure. Moreover, the identification of cluster of cases takes on special significance in suggesting a possible previous asbestos exposure, where the information collected on single cases do not imply as much. OBJECTIVES: This report concerns two cases of malignant mesothelioma that occurred in two workers employed in the same processes in a small factory that manufactured and repaired electric motors for hand tools. METHODS AND RESULTS: In the Province of Brescia (one million inhabitants) a Mesothelioma Register is in operation. The first case was classified, according to Re.Na.M.1996 criteria (National Mesothelioma Register) as "unknown" occupational exposure. The identification of a second case, that was discovered thanks to the surveillance system of the Mesothelioma Register, encouraged the local Occupational Health and Safety Service to perform a more detailed investigation that revealed, for both subjects, previously unknown occupational exposure. This consisted of grinding, in a damp setting, electric motor parts bushed with phenolic thermosetting resins reinforced with chrysotile asbestos. Moreover, weekly cleaning of the plants could have been an occasion for dust dispersion. It is likely that this exposure did not last long and was limited in extent. Other similar reports of such circumstances of occupational exposure were not available in the literature. CONCLUSIONS: The results confirm the high information value of systematic collection of incidental cases in the population, which is feasible thanks to the disease register, and the significant role of the local Occupational Health Services in demonstrating past asbestos exposure.

Clin Chest Med 2006 Jun; 27(2): 335-54 (Read article online)

West SD, Lee YC

Malignant mesothelioma is increasing in incidence globally and has no known cure. Its unique clinical feature of local infiltration along tissue planes makes it a difficult neoplasm to manage. There have been few randomized controlled trials regarding treatment options, although these have increased in recent years, and results are eagerly awaited. This article summarizes important advances in the management of mesothelioma, especially diagnostic and therapeutic aspects.

Med Lav 2005 Sep-Oct; 96(5): 440-4 (Read article online)

Petazzi A, Gaudiello F, Canti Z, Mensi C

BACKGROUND: The traditional occupational hazards of the productive cycle of oils are attributable to chemicals (use of solvents, pesticides and other agents), dusts, labour accidents (trauma, ignition, explosion), noise, manual lifting, work organization and hot-wet microclimate. The latest risk is due to the use of high temperatures (from 50 up to 250 degrees C) during the processes of extraction with solvent and refining. No cases are reported in literature of asbestos related disease in subjects who worked in oil factories. Nevertheless the structure and organization of the workplace, which is similar to that of sugar refineries, where cases of malignant mesothelioma have been described (moreover in workers employed in running and maintenance of the plants), led to the assumption that even in oil factories asbestos for the insulation of pipes and boilers could be present. OBJECTIVES: To describe 3 cases of Malignant Mesothelioma that occurred in workers of the same oil factory. METHODS: Since this occupational sector is not conventionally known for asbestos exposure the Local Health Unit and the Lombardy Mesothelioma Registry decided to investigate this industrial plant. RESULTS: Following examination of the archives of the Local Health Unit and inspection of the plant, an environmental asbestos contamination (pipes and boilers) was found. The 3 cases were defined as occupational disease and the required legal procedures were initiated. This underlines the importance of close cooperation with Local Health Units of occupational medicine and the Regional Mesothelioma Registry in the study and acknowledgment of cases which would otherwise not have been recognized, with consequent loss of precious information.

Asian Cardiovasc Thorac Ann 2006 Jun; 14(3): 206-9 (Read article online)

Clarke CP, Knight SR, Daniel FJ, Seevanayagam S

Malignant mesothelioma is a relatively rare tumor that originates in the pleural space and almost invariably results from exposure to asbestos. Between September 1989 and December 1999, 100 patients were managed with curative intent using a combination of full decortication, adjunct phototherapy after administration of hematoporphyrin derivative, and strip radiotherapy to any areas where adequate clearance was not obtained. The survival curve was compared to that of 17 matched patients treated by decortication alone. Median survival increased from 250 to 440 days in the combined treatment group.

Cancer 2006 May 17; (Read article online)

Tward JD, Wendland MM, Shrieve DC, Szabo A, Gaffney DK

BACKGROUND: Survivors of non-Hodgkin lymphoma (NHL) are at increased risk for developing secondary malignancies. For the current study, the authors quantitated this risk in a group of NHL survivors over 30 years of follow-up. METHODS: Standardized incidence ratios (observed-to-expected [O/E] ratio) and absolute excess risk of secondary malignancies were assessed in 77,876 patients who were diagnosed with NHL between 1973 and 2001 from centers that participated in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. RESULTS: There were 5638 patients who developed secondary malignancies, significantly more than the endemic rate (O/E, 1.14; P<.001). Overall, irradiated patients had a similar risk of secondary malignancies compared with unirradiated patients (relative risk, 1.04; 95% confidence interval, 0.98-1.10; P = .21). Irradiated patients had excess risk for sarcomas, breast cancers, and mesothelioma compared with unirradiated survivors (P<.05). Patients age <25 years at the time of their NHL diagnosis had the highest relative increased risk (no radiation: O/E, 2.1; P<.05; radiation: O/E, 4.51; P<.05). Overall, no statistical difference was observed for secondary cancer incidence between females and males (O/E, 1.12 vs. 1.15, respectively). Female survivors of NHL were less likely to develop breast cancer than the general population (O/E, 0.85; P<.05), but women age <25 years at the time of their NHL diagnosis were more likely to develop breast cancer (no radiation: O/E, 2.1; P<.05; radiation: O/E, 4.51; P<.05). CONCLUSIONS: The overall risk of secondary malignancies was increased for NHL survivors and varied according to age at NHL diagnosis, gender, and treatment. Cancer 2006. (c) 2006 American Cancer Society.

BMC Cancer 2006 May 17; 6(1): 130 (Read article online)

Martarelli D, Catalano A, Procopio A, Orecchia S, Libener R, Santoni G

ABSTRACT: BACKGROUND: Malignant pleural mesothelioma (MPM) is a tumor known to be resistant to conventional therapies. Thus, an in vivo model can represent an important tool for assessing the efficacy of novel approaches in the treatment of MPM. Presently, human MPM cells have been grown orthotopically in mice upon transplantation of tumor masses or tumor cell suspensions following surgery. In these models however, surgery can interfere with the tumor growth and the early stages of tumor development cannot be easily explored. Finally, results may not be so accurate due to implantation of potentially different tumor samples in different experimental groups. Our work aimed at establishing a nude mouse model xenotransplanted with human MPM cell lines in which tumor progression exhibits some features of the human disease. METHODS: Three distinct human MPM cell lines previously established from MPM patients displaying two different phenotypes, biphasic (MM-B1 and IST-Mes3) and epithelioid (IST-Mes2), were directly injected into the pleural cavity of nude mice. At different times, mice were sacrificed for autopsy, tumor nodules were counted and then removed for histology. Presence of metastases in visceral organs was also monitored. RESULTS: IST-Mes2 cells were unable to grow in nude mice. MM-B1 and IST-Mes3 cells were capable of growing in nude mice and formed tumor nodules in the pleura. Post-mortem examination showed that MPM cells progressively colonized the parietal and visceral pleura, the diaphragm, the mediastinum and, lastly the lung parenchyma. No pneumo-thorax was evidenced in the mice. Pleural effusions as well as lymph node metastases were observed only at later times. CONCLUSIONS: This model mimics the progression of human malignant mesothelioma and it is easy to perform and reproducible; therefore it can be useful to study human MPM biology and evaluate the efficacy of novel therapies.

Pneumologie 2006 May; 60(5): 277-83 (Read article online)

Scharmach M, Neumann V, Müller KM, Fischer M

Starting with the question whether there is a principal difference in the metastatic behaviour of pleural mesothelioma and pulmonary tumors, a detailed retrospective study of the findings of 210 post-mortem examinations between the years of 1992 to 1999 was conducted. The spectrum of metastatic sites is very large in malignant pulmonary carcinomas (n = 148) as well as in malignant pleural mesotheliomas (n = 62). There is no significant difference in the TMN-staging between both tumor groups at the time of death. One exception was the brain: there were significantly more metastases from the pulmonary tumors. Carcinomas metastasized more frequently into the skeleton, the kidneys and the adrenal glands, while metastases of mesotheliomas were more often found in the peritoneum. As of the moment there is no significant difference in the pattern of metastasis between both tumor groups discernible.

Neth J Med 2006 May; 64(5): 157-9 (Read article online)

Vestjens JH, Rahnama MS, Brans BT, Buijs J

We present a case of peritoneal mesothelioma that presented with fever of unknown origin and an elevation in the inflammatory parameters. Radiological imaging did not reveal a diagnosis. Because of tumour-associated inflammatory activity, indium-111 leucocyte scintigraphy enabled us to establish a diagnosis. To our knowledge, the use of indium-111 leucocyte scintigraphy in peritoneal mesothelioma has not been reported previously.

Cancer Res 2006 May 15; 66(10): 5063-8 (Read article online)

Dogan AU, Baris YI, Dogan M, Emri S, Steele I, Elmishad AG, Carbone M

Malignant mesothelioma in the western world is often associated with asbestos exposure. It is a relatively rare cancer that causes approximately 2,500 deaths yearly in the United States and 1,000 deaths yearly in the United Kingdom. In contrast, among people born in the Cappadocian (Turkey) villages of Tuzkoy, Karain, and "Old" Sarihidir, approximately 50% of deaths are caused by malignant mesothelioma. This epidemic has been attributed to erionite exposure, a type of fibrous zeolite mineral commonly found in this area of Turkey. In these three villages, malignant mesothelioma occurs in certain houses but not in others. The hypothesis was that a unique and more carcinogenic erionite was present in certain houses and caused malignant mesothelioma. We determined the X-ray diffraction pattern and the crystal structure of erionite from malignant mesothelioma villages and compared the results with the erionite samples from nearby non-malignant mesothelioma villages and from the United States. We found the same type of erionite in Cappadocian villages, with or without a malignant mesothelioma epidemic, in households with high or no incidence of malignant mesothelioma and in the United States. Pedigree studies of the three malignant mesothelioma villages showed that malignant mesothelioma was prevalent in certain families but not in others. When high-risk malignant mesothelioma family members married into families with no history of it, malignant mesothelioma appeared in the descendants. Genetically predisposed family members born and raised outside the malignant mesothelioma villages did not seem to develop malignant mesothelioma. In summary, pedigree and mineralogical studies indicate that the malignant mesothelioma epidemic is caused by erionite exposure in genetically predisposed individuals. This is the first time that genetics is shown to influence mineral fiber carcinogenesis. (Cancer Res 2006; 66(10): 5063-68).

Occup Environ Med 2006 May 12; (Read article online)

Gun RT, Pratt NL, Ryan P, Roder DM

Objectives. To update the analysis of the cohort mortality and cancer incidence study of employees in the Australian petroleum industry. Methods. Employees of Australian Institute of Petroleum member companies were enrolled in the cohort in four industry-wide surveys between 1981 and 1999. Mortality of 16547 males and 1356 females was determined up to 31 December 2001 and cancer incidence to 31 December 2000. Cause-specific mortality and cancer incidence were compared with those of the Australian population by means of Standardised Mortality Ratios (SMRs) and Standardised Incidence Ratios (SIRs). Associations between increased incidence of specific cancers and employment in the petroleum industry were tested by trends according to period of first employment, duration of employment, latency, and hydrocarbon exposure, adjusting for personal smoking history where appropriate. Results. There was a significant elevation of the incidence of mesothelioma (SIR 1.77, 95% CI 1.05-2.79), melanoma (SIR 1.37, 95% CI 1.19-1.58), and prostate cancer (SIR 1.18, 95% CI 1.04-1.34). The SIRs of all leukaemias and of acute nonlymphocytic leukaemia (ANLL) were not significantly different from unity, but all 11 ANLL cases were clustered in the middle to high hydrocarbon exposure categories. Tanker drivers had a significantly elevated incidence of kidney cancer (12 cases vs 5.84 expected, SIR 2.05, 95% CI 1.06-3.59). Lung cancer incidence was significantly reduced (SIR 0.69, 95% CI 0.57-0.83) Conclusions. Most cases of mesothelioma are probably related to past exposure to asbestos in refineries. No occupational cause has been identified for the excess of melanoma, or prostatic or bladder cancer. The possibility of a causal relationship between cancer of the kidney and hydrocarbon exposure warrants further study. It is uncertain whether benzene exposures, particularly past levels of exposure, have been high enough to cause ANLL.

Radiol Med (Torino) 2006 Apr; 111(3): 355-64 (Read article online)

Fiore D, Baggio V, Sotti G, Muzzio PC

PURPOSE: Computed tomography (CT), magnetic resonance (MR) and positron emission tomography (PET) have a very important role in the diagnosis of malignant pleural mesothelioma (MPM) in the choice of chemoradiotherapy alone or in combination with surgery and in evaluating possible recurrence. It is also essential for assessing the possible benefits of radical surgery (pleuropneumonectomy) in terms of patient survival. MATERIALS AND METHODS: We considered 28 patients suffering from MPM whose mean survival after diagnosis was 15-18 months. Sixteen of these patients had radiotherapy or chemoradiotherapy alone, according to standard protocols, while 12 also underwent surgery. The CT features of MPM were thoroughly examined, as was the role of PET and CT-PET in achieving accurate disease staging and consequent selection of candidates for surgery. RESULTS: Nine of the 12 patients who underwent pleuropneumonectomy had no significant survival advantage over the mean survival in the 16 who were not operated whereas the other three lived 1-3 years longer. Two patients underwent surgery after an optimal response to chemoradiotherapy, but both survived less than a year due to particularly aggressive recurrences. CONCLUSIONS: CT, PET and CT-PET are indicated for diagnosis and, above all, for staging of MPM, in the selection of patients who might benefit from surgery after neoadjuvant therapy and also in identifying small recurrences and/or remote metastases. Being highly specific, PET is essential in the follow-up of patients undergoing chemoradiotherapy alone and/or surgery. Each imaging modality has its advantages and limitations, but their combined use is crucial in determining the most appropriate treatment options for patients with MPM.

Hum Immunol 2006 Jan-Feb; 67(1-2): 1-12 (Read article online)

Meloni F, Morosini M, Solari N, Passadore I, Nascimbene C, Novo M, Ferrari M, Cosentino M, Marino F, Pozzi E, Fietta AM

The role of T regulatory (Treg) cells in human cancer has not yet been clarified. We assessed the presence and function of CD4(+) and CD8(+) Treg cell subsets in the peripheral blood of patients with lung cancer (LC) and pleural mesothelioma (PM). We found a low but significant increase in the number of CD4(+) T cells with phenotype and functional features of Treg cells in LC patients compared to normal healthy controls (NHC). Furthermore, total CD4(+) T cells from LC patients proliferated less than cells from controls, suggesting that the increase in the CD4(+) Treg cell pool has functional importance. LC patients also showed an expansion of the CD8(+)CD28(-) T cell subset and these cells expressed Foxp3 mRNA, as recently observed in alloantigen-specific CD8(+)CD28(-) T suppressor cells. No variation of peripheral Treg cell subsets was found in patients with PM, a disease with a predominantly localized nature. However, the lack of correlation between cancer stage and the number or the function of peripheral Treg cells in LC patients refuted the hypothesis that these cells are involved in tumor spreading. A possible involvement of the peripheral Treg cell pool in cancer development and/or in inducing systemic immunosuppression in LC patients can be hypothesized.

Int J Hyg Environ Health 2006 May 10; (Read article online)

Neri M, Taioli E, Filiberti R, Paolo Ivaldi G, Aldo Canessa P, Verna A, Marroni P, Puntoni R, Hirvonen A, Garte S

The role of CYP1A1, GSTM1, GSTT1, EPHX1, and NAT2 genotypes in susceptibility to malignant mesothelioma (MM) was compared in two case-control studies, previously conducted in two countries where different types of asbestos fibers have been used [Hirvonen et al., 1995. Inherited GSTM1 and NAT2 defects as concurrent risk modifiers in asbestos-related human malignant mesothelioma. Cancer Res. 55, 2981-2983; Hirvonen et al., 1996. Glutathione S-Transferase and N-Acetyltransferase genotypes and asbestos-associated pulmonary disorders. J. Natl. Cancer Inst.88, 1853-1856; Neri et al., 2005. Pleural malignant mesothelioma, genetic susceptibility and asbestos exposure. Mutat. Res. 592, 36-44]. Fifty-seven asbestos-exposed MM patients and 255 controls were recruited in Italy, 48 cases and 121 controls in Finland. In order to make the two studies comparable, they have been updated and new genotyping analyses have been performed. The NAT2 fast acetylator and EPHX1 low-activity genotypes were positively associated with MM in the Italian study, while they were negatively associated with this malignancy in the Finnish one. A combined significant effect was also observed in the Italian study for the NAT2 fast acetylator and EPHX1 low-activity genotypes, while this combination was protective in the Finnish study. Combination of NAT2 fast acetylator and GSTM1 null genotype posed a significantly increased risk of MM in the Italian, but not in the Finnish study. The opposite results obtained in Finland and Italy may be ascribed to random chance, but a role may be hypothesized for the fact that different types of asbestos have been used in the two countries.

Jpn J Clin Oncol 2006 Apr; 36(4): 254-7 (Read article online)

Kanazawa N, Ioka A, Tsukuma H, Ajiki W, Oshima A

BACKGROUND: Mortality statistics show rapid increase in the number of deaths from mesothelioma. However, population-based study of the incidence and the survival has never been conduced. Time-trends and regional differences in the incidence of mesothelioma in Osaka were examined together with their 5-year survival. METHODS: Individual data for mesothelioma were retrieved from Osaka Cancer Registry during the period 1966-2001. Annual incidence rates were calculated for every 3 years from 1975 to 2001, and age-standardized rates were calculated with the Japanese model population of 1985. Standardized incidence ratios were also calculated by age-specific number of population of each municipality and the corresponding age-specific incidence rates of mesothelioma in Osaka Prefecture during the period 1981-2001. The survival analysis was performed with the Kaplan-Meier method, based on the newly reported cases diagnosed during the period 1975-1997. RESULTS: Incidence rates of mesothelioma have increased rapidly both among males and females in Osaka during the past few decades. Geographical differences in the standardized incidence ratios were found to be remarkable in Osaka Prefecture. The result shows that the survival of malignant mesothelioma was very poor (5-year survival and median survival time: 5.1% and 6 months for males, 10.2% and 5 months for females). CONCLUSIONS: Incidence of mesothelioma has increased remarkably in Osaka, Japan, during past few decades. Geographical variations in the incidence were also suggested. Five-year survival of the patients was very poor.

Arch Pathol Lab Med 2006 May; 130(5): 721-4 (Read article online)

Allen TC, Moran C

Synchronous pulmonary carcinoma and pleural diffuse malignant mesothelioma is rare. Cases from the archives of 2 large referral centers were reviewed to identify cases of synchronously occurring pulmonary carcinoma and pleural diffuse malignant mesothelioma. Three cases of synchronous pulmonary carcinoma and pleural diffuse malignant mesothelioma were identified from more than 16,000 pleuropulmonary cases and were reviewed for demographic, clinical, radiographic, histologic, and immunohistochemical findings. The patients were men who were 63, 67, and 77 years old. Two had positive smoking histories; the smoking history of the other patient is unknown. One patient had a positive history of asbestos exposure; one patient had no history of asbestos exposure; and one patient's history of asbestos exposure is unknown. The patients underwent surgery for treatment of adenocarcinoma that was diagnosed preoperatively. Two of the adenocarcinomas were of a predominantly bronchioloalveolar pattern. No diffuse malignant mesothelioma was identified preoperatively. Diffuse malignant mesothelioma was suspected on the basis of pleural involvement by tumor with histology differing from that of the adenocarcinoma. Tumor immunostaining supported the diagnoses. The average survival after diagnosis was 6 weeks or less. In summary, the paucity of cases at 2 large referral centers and the paucity of cases reported in the English language literature highlights the rarity of synchronous pulmonary carcinoma and pleural diffuse malignant mesothelioma. These synchronous neoplasms occur in patients who have risk factors for both neoplasms independently. Length of survival following diagnosis is bleak.

Radiother Oncol 2006 May 12; (Read article online)

Chan MF, Chui CS, Song Y, Burman C, Yorke E, Della-Biancia C, Rosenzweig KE, Schupak K

BACKGROUND AND PURPOSE: To investigate the feasibility and potential benefits of combining electron and photon intensity modulated radiotherapy (IMRT) for patients with malignant pleural mesothelioma (MPM). PATIENTS AND METHODS: The planning CT images of 11 MPM patients, six after extrapleural pneumonectomy (EPP) and five after pleurectomy/decortication (P/D), were used for this study. These cases were planned with photon IMRT alone and photon IMRT combined with electrons (IMRT+e). The latter approach incorporated the electron dose into the inverse planning optimization. The resulting doses to the planning target volume (PTV) and relevant critical structures were compared. RESULTS: For all patients, the PTV was well covered and doses to critical structures were clinically acceptable for all patients with both techniques. However, IMRT+e exhibited a distinct advantage in reducing the doses to the liver, ipsilateral kidney, contralateral kidney, and heart (P=0.002, 0.003, 0.025, and 0.001, respectively). CONCLUSIONS: This study showed that IMRT or IMRT+e is a viable treatment modality for MPM patients. Both plans can provide excellent target coverage and normal tissue sparing, but with the addition of electron beams, the critical structures can be further spared. Additional refining of the electron contribution is expected to further reduce radiation-induced morbidity.

Mol Carcinog 2006 Apr 30; (Read article online)

Kroczynska B, Carbone M

The aim of this study was to test the possibility of using human antibodies to study the pathogenic mechanism of SV40 and asbestos in a hamster mesothelioma model. The cellular lysates from human and hamster primary mesothelial cells were tested by Western blot analysis. All of the antibodies we tested (HGF, Notch, VEGF, Sp1, p53, PP2A, p-ERK1, p-c-jun, Fra1, Fra2, MMP1, MMP9, NFkappaB p65, IkappaB, GAPDH) cross-reacted with their hamster counterparts. These data indicate that hamster mesothelioma model and more in general hamster experimental model, can be used for functional studies because many mouse, rabbit, and goat monoclonal antibodies prepared against human antigens cross-react with their hamster counterparts. (c) 2006 Wiley-Liss, Inc.

Pharmacotherapy 2006 May; 26(5): 641-54 (Read article online)

Villela LR, Stanford BL, Shah SR

Pemetrexed is a newly approved antifolate agent for the treatment of malignant pleural mesothelioma (MPM) and metastatic non-small cell lung cancer (NSCLC). We performed a PubMed/MEDLINE database search to identify relevant literature from January 1966-April 2005. Bibliographies from identified references were searched as well, as were abstracts from the 2004 and 2005 proceedings of the American Society of Clinical Oncology. We discuss the pharmacology of pemetrexed, describing its mechanism of action and comparing it with methotrexate. The pharmacokinetics and pharmacodynamics of pemetrexed are described to provide a better understanding of the properties of this drug. Therapeutic uses are assessed, beginning with the approved indications of MPM and NSCLC. However, pemetrexed has been studied in numerous phase II trials for other types of solid malignancies, and completed trials are reviewed. Data on adverse effects and drug interactions are also provided. Finally, dosing and administration are reviewed, including appropriate premedication. Premedication, including administration of steroids and vitamin supplements, has been shown to decrease the frequency and severity of pemetrexed toxicities. Pemetrexed should be used as a standard of care for unresectable MPM and recurrent metastatic NSCLC.