Treatment Of Malignant Mesothelioma Research Articles

Survival analysis of 37 cases of malignant mesothelioma

Objective: To explore the relationship between clinicopathological features, treatment and prognosis of patients with malignant mesothelioma, and provide theoretical basis for the prevention and treatment of malignant mesothelioma. Methods: In November 2022, the clinical data of 37 patients with malignant mesothelioma diagnosed in Qingdao Central Hospital from July 2014 to November 2022 were retrospectively analyzed, and the prognostic factors were analyzed by Kaplan-Meier and log-rank tests. Results: The median age of the 37 patients was 66 years old, all patients were confirmed by pathology. The median survival time of all patients was 30.00 months. The 1-year, 2-year, 3-year and 5-year cumulative survival rates were 70.27% (26/37), 48.65% (18/37), 16.22% (6/37) and 13.51% (5/37), respectively. Compared with different treatments, the median survival time of palliative care patients was 5.00 months, which was significantly lower than that of operation group (30.33 months), chemotherapy group (30.00 months), surgery combined with chemotherapy group (30.00 months) and chemotherapy combined with bevacizumab targeted therapy group (47.42 months) (P<0.05). Gender, age (≥60 years old or <60 years old), smoking history, occupational exposure history, disease site, and surgical history were not factors affecting the survival of malignant mesothelioma patients (P>0.05) . Conclusion: The clinical symptoms of malignant mesothelioma are not specific, but early initiation of treatment can still prolong survival, and chemotherapy combined with anti-vascular targeted therapy shows better therapeutic effect.

Abstract CT134: Non-viral mesothelin-targeted CAR-T cells armored with IFNg-induced secretion of PD-1 nanobody in treatment of malignant mesothelioma in phase I clinical trial

Abstract Background: Malignant pleural/peritoneal mesothelioma (MPM) is a rare, aggressive cancer with poor prognosis and high mortality of 65%-70% for pleural and 30% for peritoneal MPM. Patients who fail the standard therapy often survive less than 1 year, so it is urgent to develop new effective therapies for MPM patients. Chimeric antigen receptor (CAR)-T cells have been applied in MPM, but the efficacy was still limited due to immunosuppressive tumor microenvironment (TME). To overcome these obstacles, we developed armored CAR-T cells with nanobody targeting mesothelin (MSLN) and IFN-γ-activated secretion of PD-1 nanobody in a non-viral transposon system, named as BZDS1901. Preclinical studies have demonstrated cytotoxicity of the BZDS1901 in NCI-H226 lung/mesothelioma xenograft mouse model. To verify the safety and efficacy of BZDS1901, we conducted a single-arm, open label, dose-escalating clinical trials (NCT04503980, 05089266, 03615313) in solid tumors. Methods: Eligible patients were those who failed prior standard therapies with MSLN expression (≥50%) and PD-L1 positive in tumor specimen and voluntarily signed the informed consent. After apheresis and lymphodepletion with cyclophosphamide and fludarabine. BZDS1901 was administered intravenously in dose cohorts (1 × 106-2 × 107/kg) and the second infusion was given if no disease progression. After infusion, safety was evaluated during 28 days by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0, efficacy was assessed by RECIST 1.1 or mRECIST with CT scan. Blood CAR copies were measured by qPCR, PD-1 nanobodies and cytokines by Meso Scale Discovery method, and T cell subtypes by flow cytometry. Patients’ progression-free survival (PFS) and overall survival (OS) were measured from the day of infusion to progression or death. Results: From July 20, 2020 to December 31, 2022, 11 MPM patients were enrolled and completed the assessment, while most patients received two infusions. BZDS1901 was safe, demonstrated by 54% grade 3 and 15% grade adverse events (AEs) that were hematological side effects due to lymphodepletion and reversible with supportive care. No on-target, off-tumor toxicity and dose-limiting toxicity were observed. All patients showed expansion of CAR-T cells and increased PD-1 nanobodies in circulation. CAR-T Cmax (cp/μg) copies number was 20062, and continually detectable in blood over 4 months. PD-1 Cmax (pg/ml) was 82841, and continually detectable in blood for up to 9 months. IFN- γ and IL-6 also increased at day 4 or Day 7. All patients obtained objective tumor response, one with complete response, six with partial response, and four with stable disease. The total objective response rate was 63.64%. All enrolled patients are still alive, and mPFS and mOS are not reached. The longest PFS was up to 26 months. Median follow-up was four months. Conclusions: PD-1 nanobody secreted and MSLN targeting CAR-T cells have demonstrated promising efficacy on MPM patients. Besides CAR-T direct tumor killing activity, secreted PD-1 nanobodies may provide additional clinical benefit by invigorating CAR-T from PD-L1 inhibition, activating TILs and relieving local immunosuppression. Citation Format: Zhuqing Liu, Yong Xia, Linlin Li, Yan Sun, Zhicai Lin, Lijie Rong, Zhongzheng Zhu, Zongchang Song, Hui Xue, Jianchun Duan, Shujing Shen, Jing Wang, Linjie Lv, Yaping Yang, Xue Tan, Liping Han, Wei Zhao, Jie Wang, Wenfeng Xu, Weimin Zhu, Zhong Li, Xingya Li, Jinxing Lou, Qing Xu, Qijun Qian. Non-viral mesothelin-targeted CAR-T cells armored with IFNg-induced secretion of PD-1 nanobody in treatment of malignant mesothelioma in phase I clinical trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT134.

Reactive oxygen species in the progression and treatment of malignant mesothelioma

Malignant mesothelioma (MM) is an aggressive cancer that affects the pleural and peritoneal mesothelial lining of the lungs and abdomen. Survival rates for patients with MM remain extremely low and effective treatments are limited. MM tumors harbor both genotypic and phenotypic features that indicate MM tumor cells are under increased oxidative stress, similar to other aggressive cancers. This increased oxidative stress in MM cells supports aggressive growth while providing a therapeutic vulnerability exploitable by redox-modulating compounds. MM tumor cells also exhibit altered mitochondrial structure and function that contribute to the disease through perturbations in metabolism and reactive oxygen species (ROS) production and metabolism. Targeting the altered redox status in cancer through increasing cellular ROS levels directly or inhibiting cellular antioxidant pathways and disrupting ROS scavenging mechanisms has become an exciting area for therapeutic intervention. This review discusses ROS sources and signaling, mitochondrial structure and function and targeting mitochondria ROS as a therapeutic approach for the treatment of MM.

A novel framework for prognostic factors identification of malignant mesothelioma through association rule mining

Malignant mesothelioma (MM) is a rare cancer type arising from mesothelial cells. The current clinical diagnosis is based on contrast-enhanced computed tomography, magnetic resonance imaging, and positron emission tomography that are either invasive or costly. The failure to diagnose malignantly can lead to an increased risk of multiple medical conditions, including cardiovascular diseases, emotional distress, anemia, and diabetes. To date, there is a limited number of prognostic factors that can be used for diagnosis. Most existing work has considered the MM disease as a classification task. In contrast, our study has initiated a knowledge extraction problem and proposed a machine learning-based framework. The performance status, age, and sex of patients are currently the most substantial clinical prognostic factors, but other histopathological and clinical prognostic factors are still unclear. This study aims to search for clinical prognostic, radiological, and histopathological factors in MM. In this study, the latest dataset from a public repository (UCI) has been utilised, including patients' medical, socio-economic, histopathological, and clinical factors. Association rule mining-based algorithms (Apriori and frequent pattern (FP) growth method) and feature selection techniques have been employed to extract significant features. The performance of the proposed framework has been evaluated based on support, confidence, and lift. We set the support, confidence, and lift between 0.5–1.0, 0.5–1.0, and 1.0–1.6 respectively. Our results showed five significant prognosis factors with the values for the identification of MM: Pleural lactate dehydrogenase >500 IU/L, C-reactive protein >10/μL, pleural albumin<3/μL, the presence of asbestos exposure and pleural effusion. In nearly all the experiments, the binary features were among the leading top five features in the list. The diagnosis of MM can be accessible through prognostic factors. Our proposed framework will help to diagnose the patients without expensive tests and painful procedures. The proposed framework may assist doctors, patients, medical practitioners, and other healthcare professionals for early diagnosis and better treatment of malignant mesothelioma through significant prognostic factors.

New and old treatments for malignant mesothelioma: not just immunotherapy

Systemic therapy for malignant mesothelioma has relied on platinum and pemetrexed chemotherapy since 2003.1,2 Despite numerous clinical trials over almost two decades, no other cytotoxic chemotherapies have shown a survival benefit in this disease in the first-line or second-line treatment settings. The first positive randomised trial to utilise a maintenance agent in mesothelioma was the MAPS trial.3 This trial showed that adding the monoclonal antibody bevacizumab to chemotherapy gave a further modest survival benefit, although it was not possible to separate out the contribution of maintenance bevacizumab from that of concurrent bevacizumab with chemotherapy.

Targeting Calcium Signalling in Malignant Mesothelioma.

Calcium ions (Ca2+) are central in cancer development and growth, serving as a major signaling system determining the cell’s fate. Therefore, the investigation of the functional roles of ion channels in cancer development may identify novel approaches for determining tumor prognosis. Malignant mesothelioma is an aggressive cancer that develops from the serosal surface of the body, strictly related to asbestos exposure. The treatment of malignant mesothelioma is complex and the survival outcomes, rather than the overall survival data are, to date, disappointedly daunting. Nevertheless, conventional chemotherapy is almost ineffective. The alteration in the expression and/or activity of Ca2+ permeable ion channels seems to be characteristic of mesothelioma cells. In this review, we explore the involvement of the Ca2+toolkit in this disease. Moreover, the established sensitivity of some Ca2+channels to selective pharmacological modulators makes them interesting targets for mesothelioma cancer therapy.

Curcumin C3 complex\xae/Bioperine\xae has antineoplastic activity in mesothelioma: an in vitro and in vivo analysis

BackgroundA major limitation in the treatment for malignant mesothelioma is related to serious side effects caused by chemotherapeutics and to the development of cancer-resistance. Advances in cancer therapies have been reached thanks to the introduction of alternative approaches, such as the use of phytochemicals. Curcumin-C3complex®/Bioperine® is a commercially standardized extract containing a ratio-defined mixture of three curcuminoids and piperine that greatly increase its bioavailability. Interestingly, the anticancer effect of this formulation has been described in different studies and several clinical trials have been started, but to our knowledge none refers to human mesothelioma.MethodsCurcumin-C3complex®/Bioperine® anticancer effect was evaluated in vitro in different human mesothelioma cell lines analysing cell proliferation, colony-forming assay, wound healing assays, invasion assay and FACS analysis. In vivo anticancer properties were analysed in a mesothelioma xenograft mouse model in CD1 Nude mice.ResultsCurcumin-C3complex®/Bioperine® in vitro induced growth inhibition in all mesothelioma cell lines analysed in a dose- and time-depended manner and reduced self-renewal cell migration and cell invasive ability. Cell death was due to apoptosis. The analysis of the molecular signalling pathway suggested that intrinsic apoptotic pathway is activated by this treatment. This treatment in vivo delayed the growth of the ectopic tumours in a mesothelioma xenograft mouse model.ConclusionsCurcumin-C3complex®/Bioperine® treatment strongly reduces in vitro tumorigenic properties of mesothelioma cells by impairing cellular self-renewal ability, proliferative cell rate and cell migration and delays tumor growth in xenograft mouse model by reducing angiogenesis and increasing apoptosis. Considering that curcumin in vivo synergizes drug effects, its administration to treatment regimen may help to enhance drug therapeutic efficacy in mesothelioma. Our results suggest that implementation of standard pharmacological therapies with novel compounds may pave the way to develop alternative approaches to mesothelioma.

Survival trends in elderly patients with malignant mesothelioma: An analysis utilizing Surveillance, Epidemiology, and End Results database.

e18164 Background: Malignant mesothelioma is a highly aggressive tumor arising from the mesothelial surface. Treatment for malignant mesothelioma has not changed significantly in recent years. Better patient care may have improved survival in malignant mesothelioma patients. We conducted this study to evaluate the relative survival rates in elderly patients with malignant mesothelioma over the last one and half decades in the United States. Methods: Elderly patients (age≥65 years) diagnosed with malignant mesothelioma were selected from the Surveillance, Epidemiology, and End Results (SEER-18) database. We used Z-test to compare 1- year relative survival rates (RS) between the two time frames: 2000-2009 and 2010-2014. Several cohorts categorized by race (Caucasians and African-Americans) and gender were stratified. The survival rates were accompanied by standard errors. Results: In total, the SEER-18 database identified 6,346 patients (4,210 from 2000-2009 and 2,136 from 2010-2014; 78.3% were males, 92.6% were Caucasians). Overall, there was no improvement in survival in recent years (1-year RS: 35.4 ± 0.8 vs 36.5 ± 1.2, Z score = 1.910 on 2000-2009 &amp; 2010-2014 respectively). This was true for most of the cohort including those for males: 1-year RS: 35.0±0.9 vs 36.1±1.3, Z score = 1.569; females: 1-year RS: 37.0±1.7 vs 37.8±2.5, Z score = 1.116 and Caucasians: 1-year RS: 35.8± 0.8 vs 36.6.± 1.2, Z score = 1.512 on 2000-2009 &amp; 2010-2014 respectively. There was significant improvement in relative survival among African Americans: 1-year RS: 25.3±3.6 vs 38.6±5.6, Z score = 2.362. Conclusions: Our analysis of real-world data showed an improvement in relative survival rates for African American patients with malignant mesothelioma in recent years. This is likely related to improved delivery of care. Overall prognosis continues to remain poor and there is a strong need for novel therapeutic agents.

Orphan designation: Pegylated recombinant arginine deiminase, Treatment of malignant mesothelioma

Orphan designation: Pegylated recombinant arginine deiminase, Treatment of malignant mesothelioma

Orphan designation: Pegylated recombinant arginine deiminase, Treatment of malignant mesothelioma

Orphan designation: Pegylated recombinant arginine deiminase, Treatment of malignant mesothelioma

Orphan designation: Maytansinoid-conjugated human monoclonal antibody against mesothelin (anetumab ravtansine), Treatment of malignant mesothelioma

Orphan designation: Maytansinoid-conjugated human monoclonal antibody against mesothelin (anetumab ravtansine), Treatment of malignant mesothelioma

Double cancer comprising malignant pleural mesothelioma and squamous cell carcinoma of the lung treated with radiotherapy: A case report.

Pleurectomy/decortication (P/D) is the surgical treatment of choice for early malignant mesothelioma, but it remains unclear whether radiotherapy along with P/D should be used as multimodal treatment for this disease. We herein present the case of a 76-year-old man with a history of asbestos exposure who was diagnosed with left-sided malignant pleural mesothelioma in February 2010. The patient underwent chemotherapy with a combination of cisplatin and pemetrexed and achieved stable disease, after which time he was kept under observation. A positron emission tomography/computed tomography scan performed in February 2011 revealed nodular shadows with fluorodeoxyglucose uptake in S3 of the left lung; using bronchoscopy, the patient was diagnosed with stage IIB (cT3N0M0) primary squamous cell carcinoma. Chemoradiotherapy with vinorelbine and 60 Gy/20 fr radiotherapy was performed, and a partial response was obtained, suggesting that the radiotherapy used to treat the carcinoma of the lung may have also helped control the disease activity of the pre-existing mesothelioma. The present case indicates the value of radiotherapy in the treatment of malignant mesothelioma. The aim of the present study was to examine the possibility of new multimodal treatments for mesothelioma, along with a discussion of the relevant literature.

(-)- Epigallocatechin-3-gallate induces GRP78 accumulation in the ER and shifts mesothelioma constitutive UPR into proapoptotic ER stress.

GRP78 is a molecular chaperone of the endoplasmic reticulum (ER) that aids proper folding of nascent polypeptides. When unfolded proteins accumulate, GRP78 triggers unfolded protein response (UPR), involving activation of transcription factors like XBP1 and CHOP that may restore cell homeostasis. Increased expression of GRP78 and mild UPR can be constitutive in cancer cells, hindering apoptosis, and promoting cell survival, for example, by GRP78 relocation to the plasma membrane that activates MAPK and PI3 K/AKT pathways. These processes are thought to favor the insurgence of chemoresistance and worsen patient outcome. We have previously shown that (-)-epigallocatechin-3-gallate (EGCG) enhances ROS production and alters Ca2+ homeostasis in cell lines deriving from therapy-recalcitrant malignant mesothelioma (MMe). We consider here the EGCG impact on GRP78 and downstream factors by using qRT-PCR, Western blot, immunofluorescence, caspase assays, GRP78 siRNA silencing, and cell surface ELISA. MMe cells were found to display mild constitutive UPR, as shown by increased levels of GRP78, and presence of the protein at the cell surface, linked to AKT activation. Exposure to EGCG further increased GRP78 in the ER, and induced ATF4, spliced XBP1, CHOP, and EDEM expressions, combined with a reduction of cell surface GRP78 and a rise in caspase 3 and 8 activities. We propose that GRP78 accumulation in the ER, caused by EGCG, converts constitutive UPR of MMe cells into proapoptotic ER stress. This argues for a possible therapeutic use of EGCG in the treatment of MMe as a co-drug able to abolish chemoresistance to conventional drugs at tolerable doses.

Mesothelioma in Australia: a review.

The incidence of malignant mesothelioma in Australia is among the highest in the world as a result of widespread use of asbestos by industry and in construction throughout the 20th century. The risk of developing malignant mesothelioma after asbestos exposure is dose-related; a transient, low dose exposure confers a correspondingly very low risk of disease. Malignant mesothelioma is a heterogeneous disease, partly explaining the limited role of biomarkers in screening and diagnosis. The prognosis remains poor, and early advice on medico-legal compensation and a collaborative team approach to managing malignant mesothelioma are both essential. Chemotherapy can have a modest treatment effect in some people. New therapies, such as immunotherapy, do not yet have a defined role in the treatment of malignant mesothelioma. As treatment options for malignant mesothelioma are limited and no cure is available, there is no established role for early detection or screening of at risk populations. A multidisciplinary approach to caring for patients with malignant mesothelioma and their carers is vital.

Current Treatment of Malignant Mesothelioma

Malignant mesothelioma is a cancer of the mesothelium. Although mesothelioma is a rare malignancy, it has a poor prognosis. The incidence rate of malignant mesothelioma has been rising since the mid twentieth century century. Asbestos is the most common cause of mesothelioma. Chemotherapy combined with radiation therapy is currently the best choice of treatment and monoclonal antibody therapy is a new treatment option for the future. In the present study, we thoroughly reviewed the pathogenesis, clinical features, laboratory diagnosis, modalities of treatment, and clinical outcomes of this condition.

61: Lung sparing surgery for mesothelioma is a safe and effective modality in the treatment of malignant mesothelioma

61: Lung sparing surgery for mesothelioma is a safe and effective modality in the treatment of malignant mesothelioma

Pretreatment thrombocytosis as a significant prognostic factor in malignant mesothelioma: a meta-analysis

The current meta-analysis analyzed the prognostic impact of elevated platelet count before the treatment of malignant mesothelioma (MM). We performed a search for articles published up to April 15, 2016 in PubMed, MEDLINE, EMBASE, and Web of Science, which evaluated elevated platelet count and survival outcome of MM. STATA version 12 was used for statistical analysis. The pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) were combined to calculate overall effects. The assessment of heterogeneity was tested by the Cochran Q and I2 statistics. The sensitivity and meta-regression analyses were performed to explore the origin of heterogeneity. We analyzed 18 eligible studies (3602 patients) that evaluated the correlation between pretreatment platelet count and overall survival (OS). Elevated platelet count was a prognostic factor of poor OS, with a pooled HR of 1.56 (95% CI = 1.36–1.77). However, significant heterogeneity was observed in the included studies (I2 = 86.0%, p < 0.001). Sensitivity and meta-regression analyses were performed to trace the origin of heterogeneity. Only the variable type (multivariable or univariate model) was traced as the origin of heterogeneity. Hence, we conducted a subgroup analysis of variable type. The HR was 1.66 (95% CI = 1.41–1.91) in the multivariable group and no significant heterogeneity was observed (I2 = 0.0%, p = 0.476). In conclusion, high pretreatment platelet count resulted in poor OS in MM. Therefore, platelet count could be an adequate and useful factor of prognosis for MM.

Abstract 5174: Modeling mesothelioma initiation through disruption of the Hippo pathway revealed involvement of PLCB4 in YAP-driven mesothelioma cell proliferation

Abstract Disruption of the Hippo pathway as a result of deletion and/or mutation of the involved genes (e.g., neurofibromin 2 [NF2]) is frequently observed in mesothelioma. The disruption results in reduced phosphorylation of yes-associated protein (YAP), and the non-phosphorylated YAP translocates to the nucleus and regulates gene expression. While the roles of the disrupted Hippo pathway in the maintenance of established tumors have been investigated using mesothelioma cell lines, its involvement in the initiation of mesothelioma remains unclear. We used immortalized human mesothelial cells to study the transformation process, and found that NF2 knockdown led to transformation of the cells concurrently with reduction in YAP phosphorylation. The cells exhibited enhanced growth in vitro, and formed tumors following transplantation into nude mice. Similar results to those obtained by NF2 knockdown were also obtained using enforced expression of wild-type (wt) or constitutively active (S127A) YAP. Although enforced expression of YAPwt or YAPS127A was insufficient to transform primary (unimmortalized) human mesothelial cells, our findings provide evidence for the crucial roles of activated YAP in the transformation of mesothelial cells. To identify YAP-regulated genes critical for mesothelial tumorigenesis, we conducted gene expression analysis comparing control- and YAP-transduced immortalized human mesothelial cells. Gene Set Enrichment Analysis (GSEA) using a gene set down-regulated by YAP knock-down in mesothelioma cell lines revealed phospholipase C beta 4 (PLCB4) to be among the top-ranking genes up-regulated by YAP in our experiments. PLCB4 was up-regulated by YAP in immortalized human mesothelial cells, and down-regulated by YAP knock-down in YAP-driven mesothelioma cells. shRNA-mediated silencing of PLCB4 attenuated the growth of YAP-transduced mesothelial cells and Hippo-disrupted, but not -proficient, mesothelioma cell lines. Our model system thus provides a versatile tool to investigate the mechanisms underlying mesothelioma development. We suggest that PLCB4 may be an attractive drug target for the treatment of malignant mesothelioma. Citation Format: tatsuo kakiuchi. Modeling mesothelioma initiation through disruption of the Hippo pathway revealed involvement of PLCB4 in YAP-driven mesothelioma cell proliferation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5174.

Pharmacokinetics and the effect of heat on intraperitoneal pemetrexed using a murine model

BackgroundPemetrexed is a systemic chemotherapeutic agent used in the treatment of malignant mesothelioma. This drug represents a potentially promising intraperitoneal (IP) agent to use for hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal mesothelioma. However, this has yet to be supported by preclinical studies. Therefore, we aimed to study the effect of pemetrexed dose and perfusion temperature on the resultant pemetrexed concentration in 3 different compartments (systemic circulation, portal circulation and peritoneal tissues) using a murine model. MethodsUnder general anesthesia, 29 Sprague-Dawley rats were submitted to 3 different doses of IP pemetrexed (500, 1000 and 1500 mg/m2) combined with 3 different perfusion temperatures (37, 40 and 43 °C) for a total duration of 25 min. At the end of perfusion, samples in different compartments (systemic circulation, portal circulation and peritoneum) were harvested and concentrations of pemetrexed were measured using high performance liquid chromatography. ResultsWith increasing dose of IP pemetrexed, higher concentrations were measured in the 3 compartments tested. In peritoneal cells, the difference between IP doses of 500 and 1000 mg/m2 (2.03 vs. 19.17 μg/g, p < 0.001) was greater than the difference between 1000 and 1500 mg/m2 (19.17 vs. 22.80 μg/g, p = 0.027). When the perfusion temperature increased, we observed a proportional rise of pemetrexed concentration in both the portal and systemic compartments; while in the peritoneal cells, the pemetrexed concentration increased up to 40 °C, after which it plateaued. ConclusionBoth heat and increasing doses of IP pemetrexed enhance peritoneal cell concentration of pemetrexed. However, for temperatures above 40 °C, pemetrexed concentration reached a plateau in peritoneal cells. Systemic and portal concentrations increased proportionally with both increasing temperatures and IP doses. We believe these results should be taken into consideration for the design of an eventual clinical study in humans.

89 Experience of the treatment of malignant mesothelioma at a UK centre

89 Experience of the treatment of malignant mesothelioma at a UK centre