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EC proposes tightening carcinogen regulations
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On Jan 10, 2017, the European Commission (EC) announced plans to introduce regulations on occupational exposure to seven carcinogenic chemicals. The targeted agents included epichlorohydrin, which is used to make plastics, epoxy glues, and resins, and is associated with lung cancer. The EC proposed an occupational exposure limit of 1·9 mg/m³. An estimated 39 372 European Union workers are exposed to epichlorohydrin. It is scheduled to be included in amendments to the 2004 Carcinogens and Mutagens Directive (CMD), which establishes limits and other measures to minimise occupational exposure to hazardous materials In addition to the seven chemicals named in January, in 2016 the EC proposed to add a further 13 substances to the CMD. Among these were chromium VI compounds
and hydrazine, both of which cause lung cancer. Over 3 million European Union workers are thought to come into contact with these chemicals. The EC also suggested an occupational exposure limit of 0·1 mg/m³ for respirable silica dust. Such a measure would help protect around 5·3 million workers, primarily in construction, from lung cancer and silicosis. The European Parliament has yet to vote on both sets of proposed amendments to the CMD, but is expected to do so later this year. “We think we can save more than 100 000 lives over the next 50 years with these changes”, a spokesperson for the EC told The Lancet Respiratory Medicine. But there was one notable absence from the list of carcinogens. The EC opted to withhold action on diesel exhaust emissions. The decision was partly down to the difficulty in establishing a
legal limit that takes into account the difference between older diesel engines and cleaner, newer ones. Moreover, diesel emissions are a complex mixture of all kinds of chemicals, and exposure is widespread outside the workplace. “Laws, policy, and investment de cisions are for governments to decide”, said WHO’s Carlos Dora (Geneva, Switzerland). “Still, there is no doubt that occupation is an important source of exposure to diesel emissions, or that setting regulation for workers would benefit everyone, not least by encouraging a shift to cleaner technologies.” But he stressed the need for a comprehensive package of measures, both in the European Union and in those parts of the world where occupational legislation is either nonexistent or widely ignored.
Lewis Houghton/Science Photo Library
EC proposes tightening carcinogen regulations
Published Online March 8, 2017 http://dx.doi.org/10.1016/ S2213-2600(17)30084-X
Talha Khan Burki
Patients with non-small-cell lung cancer (NSCLC) who also have the T790M mutation have significantly longer progression-free survival (PFS) when treated with osimertinib compared with standard platinum-based chemotherapy, according to results from a phase 3 trial. Prof Tony Mok (Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong) and colleagues randomly assigned 419 patients with T790M-positive NSCLC to receive either oral osimertinib alone (n=279) or intravenous pemetrexed with carboplatin or cisplatin (n=140) every 3 weeks, for up to six cycles of treatment. Median duration of PFS was 10·1 months for the osimertinib group versus 4·4 months for the platinum–pemetrexed group (hazard ratio [HR] 0·30, 95% CI 0·23–0·41; p<0·001). All patients previously had disease progression after first-line treatment with epidermal growth factor receptor–tyrosine kinase inhibitors www.thelancet.com/respiratory Vol 5 April 2017
(EGFR–TKIs). According to Mok, “this is the first randomised phase 3 study that confirmed the superiority of osimertinib over standard chemotherapy in patients with T790M mutation and EGFR–TKI failure”. He continued: “osimertinib is now the new standard for this patient population”. About 60% of patients with NSCLC have T790M mutations in EGFR, resulting in resistance to many of the clinically available EGFR–TKIs. Third-generation EGFR–TKIs, such as osimertinib, show greater potency against EGFR mutants than against wild-type receptors, compared with previous generations. According to Mok, osimertinib also has better CNS penetration than other EGFR–TKIs, leading the authors to look at PFS in patients with CNS metastases at presentation. Osimertinib improved PFS in this subgroup (median 8·5 months for osimertinib vs 4·2 months for platinum–pemetrexed; HR 0·32, 95% CI 0·21–0·49), although participants who
did not present with CNS metastases were not regularly monitored for disease progression in the CNS. Commenting on the findings, Charles Swanton (Crick Institute, London, UK) said: “Importantly, osimertinib appeared to control CNS disease better than did chemotherapy”, and that overall, osimertinib had less severe toxicities than chemotherapy, which is “a crucial consideration in the palliative setting.” “Considering cancers within evo lutionary frameworks is becoming increasingly relevant in the design of new therapies and clinical trials”, added Swanton. “By understanding evolutionary routes of resistance to first-line therapies in cancer, small molecules can be developed that offer patients meaningful clinical benefit, and that tackle emerging drug-resistant mutations to improve PFS relative to standard of care.”
Dr Tim Evans/Science Photo Library
Osimertinib improves progression-free survival in NSCLC
Published Online March 8, 2017 http://dx.doi.org/10.1016/ S2213-2600(17)30085-1 For more on the osimertinib trial see N Engl J Med 2017; 376: 629–40
Sheila Pinion 251
On Jan 10, 2017, the European Commission (EC) announced plans to introduce regulations on occupational exposure to seven carcinogenic chemicals. The targeted agents included epichlorohydrin, which is used to make plastics, epoxy glues, and resins, and is associated with lung cancer. The EC proposed an occupational exposure limit of 1·9 mg/m³. An estimated 39 372 European Union workers are exposed to epichlorohydrin. It is scheduled to be included in amendments to the 2004 Carcinogens and Mutagens Directive (CMD), which establishes limits and other measures to minimise occupational exposure to hazardous materials In addition to the seven chemicals named in January, in 2016 the EC proposed to add a further 13 substances to the CMD. Among these were chromium VI compounds
and hydrazine, both of which cause lung cancer. Over 3 million European Union workers are thought to come into contact with these chemicals. The EC also suggested an occupational exposure limit of 0·1 mg/m³ for respirable silica dust. Such a measure would help protect around 5·3 million workers, primarily in construction, from lung cancer and silicosis. The European Parliament has yet to vote on both sets of proposed amendments to the CMD, but is expected to do so later this year. “We think we can save more than 100 000 lives over the next 50 years with these changes”, a spokesperson for the EC told The Lancet Respiratory Medicine. But there was one notable absence from the list of carcinogens. The EC opted to withhold action on diesel exhaust emissions. The decision was partly down to the difficulty in establishing a
legal limit that takes into account the difference between older diesel engines and cleaner, newer ones. Moreover, diesel emissions are a complex mixture of all kinds of chemicals, and exposure is widespread outside the workplace. “Laws, policy, and investment de cisions are for governments to decide”, said WHO’s Carlos Dora (Geneva, Switzerland). “Still, there is no doubt that occupation is an important source of exposure to diesel emissions, or that setting regulation for workers would benefit everyone, not least by encouraging a shift to cleaner technologies.” But he stressed the need for a comprehensive package of measures, both in the European Union and in those parts of the world where occupational legislation is either nonexistent or widely ignored.
Lewis Houghton/Science Photo Library
EC proposes tightening carcinogen regulations
Published Online March 8, 2017 http://dx.doi.org/10.1016/ S2213-2600(17)30084-X
Talha Khan Burki
Patients with non-small-cell lung cancer (NSCLC) who also have the T790M mutation have significantly longer progression-free survival (PFS) when treated with osimertinib compared with standard platinum-based chemotherapy, according to results from a phase 3 trial. Prof Tony Mok (Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong) and colleagues randomly assigned 419 patients with T790M-positive NSCLC to receive either oral osimertinib alone (n=279) or intravenous pemetrexed with carboplatin or cisplatin (n=140) every 3 weeks, for up to six cycles of treatment. Median duration of PFS was 10·1 months for the osimertinib group versus 4·4 months for the platinum–pemetrexed group (hazard ratio [HR] 0·30, 95% CI 0·23–0·41; p<0·001). All patients previously had disease progression after first-line treatment with epidermal growth factor receptor–tyrosine kinase inhibitors www.thelancet.com/respiratory Vol 5 April 2017
(EGFR–TKIs). According to Mok, “this is the first randomised phase 3 study that confirmed the superiority of osimertinib over standard chemotherapy in patients with T790M mutation and EGFR–TKI failure”. He continued: “osimertinib is now the new standard for this patient population”. About 60% of patients with NSCLC have T790M mutations in EGFR, resulting in resistance to many of the clinically available EGFR–TKIs. Third-generation EGFR–TKIs, such as osimertinib, show greater potency against EGFR mutants than against wild-type receptors, compared with previous generations. According to Mok, osimertinib also has better CNS penetration than other EGFR–TKIs, leading the authors to look at PFS in patients with CNS metastases at presentation. Osimertinib improved PFS in this subgroup (median 8·5 months for osimertinib vs 4·2 months for platinum–pemetrexed; HR 0·32, 95% CI 0·21–0·49), although participants who
did not present with CNS metastases were not regularly monitored for disease progression in the CNS. Commenting on the findings, Charles Swanton (Crick Institute, London, UK) said: “Importantly, osimertinib appeared to control CNS disease better than did chemotherapy”, and that overall, osimertinib had less severe toxicities than chemotherapy, which is “a crucial consideration in the palliative setting.” “Considering cancers within evo lutionary frameworks is becoming increasingly relevant in the design of new therapies and clinical trials”, added Swanton. “By understanding evolutionary routes of resistance to first-line therapies in cancer, small molecules can be developed that offer patients meaningful clinical benefit, and that tackle emerging drug-resistant mutations to improve PFS relative to standard of care.”
Dr Tim Evans/Science Photo Library
Osimertinib improves progression-free survival in NSCLC
Published Online March 8, 2017 http://dx.doi.org/10.1016/ S2213-2600(17)30085-1 For more on the osimertinib trial see N Engl J Med 2017; 376: 629–40
Sheila Pinion 251