Modest Results for Checkpoint Agents in Mesothelioma

Chicago— Two trials presented at the 2016 annual meeting of the American Society of Clinical Oncology (ASCO) provide somewhat discouraging findings on checkpoint inhibitors for second-line treatment of mesothelioma.

In the largest checkpoint inhibitor study in mesothelioma to date, a Phase IB study conducted with the programmed death ligand-1 (PD-L1) inhibitor avelumab (Pfizer), the objective response rate (ORR) among the 53 patients in the study, who had unresectable pleural or peritoneal mesothelioma that had progressed after chemotherapy, was 9.4%, and 47.2% achieved stable disease (abstract 8503). The median progression-free survival was 17.1 weeks, but several responders remain on avelumab and are being followed for long-term benefit, reported Raffit Hassan, MD, the head of the thoracic and solid tumor immunotherapy section of the National Cancer Institute, in Bethesda, Md.

Although the ORR has been closer to 30% in smaller and previously reported studies with the programmed death-1 (PD-1) inhibitors pembrolizumab (Keytruda, Merck) and nivolumab (Opdivo, Bristol-Myers Squibb), the ASCO-invited discussant of the study, Tom John, MBBS, PhD, a senior investigator in thoracic oncology at the Olivia Newton-John Cancer Research Institute, in Melbourne, Australia, suggested the studies have been relatively consistent. “There is a signal for efficacy in mesothelioma, but these studies are also a reality check,” Dr. John reported. With a PD-1 inhibitor monotherapy, “most patients do not seem to benefit.”

Source: Modest Results for Checkpoint Agents in Mesothelioma


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Court rejects $8M verdict in asbestos case

Pointing to problems with expert witnesses, an appeals court Wednesday rejected an $8 million verdict in a case filed by a man who said he suffered mesothelioma because of exposure to asbestos in cigarette filters and in other products.

A panel of the 4th District Court of Appeal ordered a new trial for R.J. Reynolds Tobacco Co. and a “directed” verdict in favor of Crane Co., a manufacturing company.

It ruled against Richard DeLisle, who won the verdict in the Broward County case.

DeLisle alleged that he was exposed to asbestos in filters of Kent cigarettes he smoked in the 1950s.

R.J. Reynolds is a successor company to the manufacturer of Kent cigarettes.

He also alleged exposure in the 1960s in a workplace through sheet gaskets used by Crane Co., a valve and pump manufacturer, the ruling said.

[Article continues at original source]

Source: Court rejects $8M verdict in asbestos case


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Arginine deprivation shows promise for malignant pleural mesothelioma

Arginine deprivation with pegylated arginine deiminase may improve PFS and prolong life expectancy in patients with argininosuccinate synthetase 1–deficient malignant pleural mesothelioma, according to the results of a randomized phase 2 trial.

The incidence of malignant pleural mesothelioma has risen in the United States and in Europe. The disease has a median survival from diagnosis of less than 1 year, and few validated treatment options exist.

“To our knowledge, we were the first to show that an exogenous supply of the amino acid arginine is critical for the survival of mesothelioma cell lines displaying loss of the urea cycle and arginine biosynthetic enzyme argininosuccinate synthetase 1 (ASS1),” Peter W. Szlosarek, MD, PhD, clinical senior lecturer at Barts Cancer Institute and Barts and The London School of Medicine and Dentistry, in London, and colleagues wrote. “Various ASS1–negative tumors have been shown to be sensitive to arginine depleters, mycoplasmal-derived pegylated arginine deiminase (ADI-PEG20, Polaris Group) and recombination human arginases, in preclinical studies.”

[Article continues at ariginal source]

Source: Arginine deprivation shows promise for malignant pleural mesothelioma


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Asbestos and product defence science

In 2015, the Collegium Ramazzini, an independent, international academy of experts in occupational and environmental health, released three statements on asbestos.1–3 The documents are focused on the only form of asbestos remaining in use, i.e. chrysotile (white asbestos). The Collegium is concerned by the persisting use of chrysotile in many countries taking place in spite of the evidence of its carcinogenicity and the calls for a ban by the World Health Organization, the International Labour Organization and the Collegium itself as well as other institutions over the past decades.

Currently, over half of the world’s population is extracting and/or using 2 million tons of asbestos annually, mostly in low- and middle-income countries. Asia has become the largest asbestos consumer in the world and Russia, Kazakhstan and Brazil have become the largest asbestos exporters. As late as 2015, the major producers and users of asbestos opposed the inclusion of chrysotile among substances covered by the Rotterdam Convention on the Prior Informed Consent Procedure for Certain Hazardous Chemicals and Pesticides in International Trade….

The Collegium notes that the reluctance to stop using asbestos is a consequence of ‘the corrupting influence of pro-chrysotile lobbies employing product defence science’. This term encompasses research activities whose goals are not scientific knowledge but to influence policy decisions on the use of an industrial product….

[Article continues at original source]

Source: Asbestos and product defence science

 


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Asbestos exposure and histological subtype of malignant mesothelioma

Abstract

Background   Malignant mesothelioma (MM) has distinct histological subtypes (epithelioid, sarcomatoid and biphasic) with variable behaviour and prognoses. It is well recognised that survival time varies with the histological subtype of MM. It is not known, however, if asbestos exposure characteristics (type of asbestos, degree of exposure) are associated with different histological subtypes.

Aim   To determine if the pathological MM subtype is associated with the type of asbestos or the attributes of asbestos exposure.Methods Cases of MM for the period 1962 until 2012, their main histological subtype and their most significant source of asbestos exposure were collected from the Western Australian Mesothelioma Registry. Exposure characteristics included, degree of asbestos exposure (including total days exposed, years since first exposure and, for crocidolite only, calculated cumulative exposure), source of exposure (occupational or environmental), form of asbestos handled (raw or processed) and type of asbestos (crocidolite only or mixed fibres).

Results   Patients with the biphasic subtype were more likely to have occupational exposure (OR 1.83, 1.12 to 2.85) and exposure to raw fibres (OR 1.58, 1.19 to 2.10). However, differences between subtypes in the proportions with these different exposure characteristics were small and unlikely to be biologically relevant. Other indicators of asbestos exposure were not associated with the histological subtype of mesothelioma.

Conclusions   There was no strong evidence of a consistent role of asbestos exposure indicators in determining the histological subtype of MM.

Source: Asbestos exposure and histological subtype of malignant mesothelioma

 


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Whitley Bay grandad diagnosed with same asbestos-related cancer that killed his dad

A former teacher who watched his own father die of asbestos-related cancer has spoken of his devastation at finding out he has the same disease.

Adrian Starr was diagnosed with the terminal illness, mesothelioma, in October last year and says his only hope now is if medics are able to find a cure.

The 67-year-old, a dad of two and granddad of three, is a retired teacher who worked at various schools across the North East, but believes his exposure to the deadly fibres may date back as far as the 1970s when he worked for one summer at the same paper mill as his father in Kent.

Adrian, from Whitley Bay, said: “I was only there for a short period, but that is where my father was exposed to asbestos dust.

“He was a maintenance engineer and worked in dirty, dusty areas where pipes lagged with asbestos ran across the ceiling and underneath the floor.

“I worked in a different area, but I remember often having tea from a flask we’d brought from home sitting with my dad at his end of the factory.

“I don’t know whether the damage was done there or at one of the schools where I worked.”

[Article continues at original source]

Source: Whitley Bay grandad diagnosed with same asbestos-related cancer that killed his dad

 


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Federal Law Preempts State Claims in Asbestos Case

The estate of a New Jersey woman who died of mesothelioma—possibly caused by physical contact with her father, who worked for a rapid transit system, and his asbestos-covered clothes—cannot sue the transportation system in state court, an appeals panel has ruled.

Any state tort claims the estate may have against the key defendants—the Delaware River Port Authority (DRPA) and its subsidiary, the Port Authority Transit Corp.—are pre-empted by federal laws governing locomotives, the three-judge Appellate Division panel said in a published ruling Nov. 19.

The same federal law that governs locomotives also pre-empts claims against the manufacturers and distributors of the locomotives’ brakes, which the woman’s father worked on while employed by PATCO, the court said.

“Since 1926, it has been settled that in enacting the Locomotive Inspection Act … Congress intended to occupy the entire field of locomotive equipment,” wrote Appellate Division Judge Carmen Alvarez in Brust v. ACF Industries.

“Congress thereby pre-empted both state legislation that would affect the design, construction, and material of every part of the locomotive and its appurtenances … and state law tort claims for defective design of locomotive equipment.”

[Article continues at original source]

Source: Federal Law Preempts State Claims in Asbestos Case


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Prophylactic Radiotherapy for the Prevention of Procedure-Tract Metastases in Malignant Pleural Mesothelioma

TAKE-HOME MESSAGE

This multicenter, open-label phase III study evaluated the utility of prophylactic radiation to prevent procedure-tract metastases in 203 patients with malignant pleural mesothelioma. No significant differences were observed in procedure-tract metastases incidence in those who received immediate radiotherapy vs those receiving deferred radiation therapy.

Routine universal prophylactic radiotherapy to prevent procedure-tract metastases in patients with malignant pleural mesothelioma offers no clear clinical benefit.

BACKGROUND

The use of prophylactic radiotherapy to prevent procedure-tract metastases (PTMs) in malignant pleural mesothelioma remains controversial, and clinical practice varies worldwide. We aimed to compare prophylactic radiotherapy with deferred radiotherapy (given only when a PTM developed) in a suitably powered trial.

[Article continues at original source]

Source: Prophylactic Radiotherapy for the Prevention of Procedure-Tract Metastases in Malignant Pleural Mesothelioma

 


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Patient health, not age, should dictate treatment for mesothelioma, University academic says

A 17 year-long study conducted at Glenfield Hospital, Leicester, suggests surgical benefits are evident in both young and old

The conclusion of a study by a University team at Glenfield Hospital, Leicester, which took place between 1999 and 2015, has suggested that age is not as important in determining treatment options for mesothelioma as previously thought.

Miss Annabel Sharkey, a cardiothoracic surgeon and Clinical Fellow in the Department of Cancer Studies at the University, presented the findings of the study at the 2016 European Lung Cancer Conference in Geneva, Switzerland.

Miss Sharkey said: “Patients have to be fit enough, not just to withstand the operation, but the follow-up therapy as well. Surgeons when selecting their patients, also have to keep the oncologist’s treatment in mind.

“The main thing is, not to discount the idea of surgery just because you’re older. People generally are more fit today than they once were, and that allows more people to benefit from surgery.”

[Article continues at original source]

Source: Patient health, not age, should dictate treatment for mesothelioma, University academic says

 


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Dying and living with killer dust

Bruno Comelli died of a broken heart, says his adoring wife Edda. He’d survived Nazis and post-war poverty in Italy before arriving in Melbourne. There he worked seven days a week as a fruiterer and concreter to give his children the education he never had.

In his late 70s Bruno was fit, strong, and savouring the life he had made for his family in his beloved Australia. Then, after all he’d been through and fought for, he was cut down by the deadly lung cancer, mesothelioma, a result of exposure to stray asbestos fibres decades previously.

Bruno hadn’t worked with asbestos. Like many poor migrants he had lived in Melbourne’s west when it was the city’s smelly, industrial engine room. His home was just down the road from James Hardie’s Brooklyn asbestos plant. Twice a week he’d take his greengrocer’s rubbish to local tips and throw it into pits through clouds of white dust. “He used to say it was horrible down there,” says Edda. “Especially on a windy day”.

Decades after the Hardie factory closed, Bruno died in 2012 aged 80, a likely victim of environmental exposure to waste asbestos.

Source: Dying and living with killer dust


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