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Fertility drugs and childhood leukaemia: is there a link?
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A new study by scientists in France has suggested that fertility drugs could be linked with a heightened risk of childhood leukaemia. The widely publicised study—which involved 2445 children and their mothers— concluded that children conceived after the use of ovarian-stimulating drugs were 2·6 times more likely to develop acute lymphoblastic leukaemia (ALL) and 2·3 times more likely to develop acute myeloid leukaemia. Presenting the findings at the Childhood Cancer 2012 conference in London, UK, lead author Jeremie Rudant (Center for Research in Epidemiology and Population Health, INSERM, Villejuif, France) noted that this “is the first time that a specific increased risk linked to fertility drugs has been found”. Children who were conceived naturally after their mothers had failed to become pregnant for more than a year were found to be
at 50% increased risk of ALL. No heightened risk of leukaemia was associated with in-vitro fertilisation (IVF) or artificial insemination. Simon Fishel (CARE Fertility Group, Nottingham, UK) is sceptical. He points out that patients undergoing IVF also take fertility drugs. “They’re probably more potently used in IVF—for higher doses and for longer periods than you may have if you’re not on IVF”. In which case, how is it possible to posit a link between fertility drugs and leukaemia in one group of patients, but not in another? “It is a major shortcoming and it is very difficult to explain it”, Fishel said. Moreover, the French study is not backed by a publication. “We have to be very circumspect because this hasn’t gone through the peer-review process”, cautions Richard McNally (Newcastle University, Newcastle, UK). Without scrutiny from fellow experts, questions
remain over the robustness of the methods and possible bias in selection of the control group. “The findings would also have to be replicated in a study of greater or similar size”, added McNally. Until all this happens, he does not believe it is possible to draw any conclusions from the research. The Human Fertilisation and Embryology Authority (HFEA), which regulates the UK’s assisted reproduction industry, has given permission for researchers at University College London to link its data on treatment cycles to a cancer registry in order to investigate the association between such treatment and site-specific risks of cancer incidence. “We ought to be getting more data on this area of research over the next year or so”, the HFEA’s Juliet Tizzard told The Lancet Oncology.
Zephyr/Science Photo Library
Fertility drugs and childhood leukaemia: is there a link?
Published Online May 4, 2012 DOI:10.1016/S14702045(12)70202-4 For more on the Childhood Cancer 2012 conference see http://www.childhoodcancer 2012.org.uk/
Talha Khan Burki
Second-line everolimus treatment in advanced renal-cell cancer Patients with metastatic renal-cell cancer who discontinued treatment with vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR TKIs) because of toxicities were able to tolerate and benefited from second-line treatment with everolimus with no additional toxicities, according to a retrospective subgroup analysis of the phase 3 RECORD-1 trial. Risk of disease progression was reduced by 67% for patients taking everolimus, an mTOR inhibitor, compared with those on placebo. In 58 VEGFR-TKI-intolerant patients (14% of the total number), median progression-free survival was 5·4 months with everolimus and 1·9 months with placebo. For 26 patients who were intolerant to the multitargeted receptor tyrosine kinase sunitinib, median progression-free survival was 5·1 months with everolimus and www.thelancet.com/oncology Vol 13 June 2012
2·8 months for placebo. Grade 3 or 4 toxicities seen in everolimus-treated patients were infections, fatigue, and stomatitis, which were similar to those seen in the larger patient pool. Toxicities associated with VEGFRTKI treatment include hypertension, hand-foot reaction, rash or desquamation, alopecia, diarrhoea, fatigue, hyponatraemia, and thrombocytopenia, and frequently necessitate dose interruptions, reductions, or discontinuation of treatment. “The clinical challenge in metastatic renal-cell cancer is that many patients are intolerant to first-line therapy, and patients need to be treated numerous times for this disease. We found that everolimus, which has a different molecular target and mechanism of action than the VEGFR TKIs, was as effective in both patients who were intolerant to VEGFR TKIs and in the larger group”, said study researcher
Robert Figlin (Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, USA). The safety profile of mTOR inhibitors does not generally overlap with that of VEGFR TKIs, and cardiovascular toxicities and hand-foot reactions are not usually seen in everolimus-treated patients, Figlin added. “The two drug classes may in fact be targeting the same pathway, and may have a similar mechanism of action, which may be why the outcomes in terms of progression-free survival were so similar”, said David Nanus (Weill Cornell Medical College, New York, NY, USA). “But the most important lesson from this study is that everolimus has less toxicity and similar benefit to VEGFR TKIs in this patient population, who need to be treated repeatedly”, Nanus said.
Published Online May 4, 2012 DOI:10.1016/S14702045(12)70203-6 For the RECORD-1 subgroup analysis see Br J Cancer 2012; 106: 1475–80
Vicki Brower e235
A new study by scientists in France has suggested that fertility drugs could be linked with a heightened risk of childhood leukaemia. The widely publicised study—which involved 2445 children and their mothers— concluded that children conceived after the use of ovarian-stimulating drugs were 2·6 times more likely to develop acute lymphoblastic leukaemia (ALL) and 2·3 times more likely to develop acute myeloid leukaemia. Presenting the findings at the Childhood Cancer 2012 conference in London, UK, lead author Jeremie Rudant (Center for Research in Epidemiology and Population Health, INSERM, Villejuif, France) noted that this “is the first time that a specific increased risk linked to fertility drugs has been found”. Children who were conceived naturally after their mothers had failed to become pregnant for more than a year were found to be
at 50% increased risk of ALL. No heightened risk of leukaemia was associated with in-vitro fertilisation (IVF) or artificial insemination. Simon Fishel (CARE Fertility Group, Nottingham, UK) is sceptical. He points out that patients undergoing IVF also take fertility drugs. “They’re probably more potently used in IVF—for higher doses and for longer periods than you may have if you’re not on IVF”. In which case, how is it possible to posit a link between fertility drugs and leukaemia in one group of patients, but not in another? “It is a major shortcoming and it is very difficult to explain it”, Fishel said. Moreover, the French study is not backed by a publication. “We have to be very circumspect because this hasn’t gone through the peer-review process”, cautions Richard McNally (Newcastle University, Newcastle, UK). Without scrutiny from fellow experts, questions
remain over the robustness of the methods and possible bias in selection of the control group. “The findings would also have to be replicated in a study of greater or similar size”, added McNally. Until all this happens, he does not believe it is possible to draw any conclusions from the research. The Human Fertilisation and Embryology Authority (HFEA), which regulates the UK’s assisted reproduction industry, has given permission for researchers at University College London to link its data on treatment cycles to a cancer registry in order to investigate the association between such treatment and site-specific risks of cancer incidence. “We ought to be getting more data on this area of research over the next year or so”, the HFEA’s Juliet Tizzard told The Lancet Oncology.
Zephyr/Science Photo Library
Fertility drugs and childhood leukaemia: is there a link?
Published Online May 4, 2012 DOI:10.1016/S14702045(12)70202-4 For more on the Childhood Cancer 2012 conference see http://www.childhoodcancer 2012.org.uk/
Talha Khan Burki
Second-line everolimus treatment in advanced renal-cell cancer Patients with metastatic renal-cell cancer who discontinued treatment with vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR TKIs) because of toxicities were able to tolerate and benefited from second-line treatment with everolimus with no additional toxicities, according to a retrospective subgroup analysis of the phase 3 RECORD-1 trial. Risk of disease progression was reduced by 67% for patients taking everolimus, an mTOR inhibitor, compared with those on placebo. In 58 VEGFR-TKI-intolerant patients (14% of the total number), median progression-free survival was 5·4 months with everolimus and 1·9 months with placebo. For 26 patients who were intolerant to the multitargeted receptor tyrosine kinase sunitinib, median progression-free survival was 5·1 months with everolimus and www.thelancet.com/oncology Vol 13 June 2012
2·8 months for placebo. Grade 3 or 4 toxicities seen in everolimus-treated patients were infections, fatigue, and stomatitis, which were similar to those seen in the larger patient pool. Toxicities associated with VEGFRTKI treatment include hypertension, hand-foot reaction, rash or desquamation, alopecia, diarrhoea, fatigue, hyponatraemia, and thrombocytopenia, and frequently necessitate dose interruptions, reductions, or discontinuation of treatment. “The clinical challenge in metastatic renal-cell cancer is that many patients are intolerant to first-line therapy, and patients need to be treated numerous times for this disease. We found that everolimus, which has a different molecular target and mechanism of action than the VEGFR TKIs, was as effective in both patients who were intolerant to VEGFR TKIs and in the larger group”, said study researcher
Robert Figlin (Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, USA). The safety profile of mTOR inhibitors does not generally overlap with that of VEGFR TKIs, and cardiovascular toxicities and hand-foot reactions are not usually seen in everolimus-treated patients, Figlin added. “The two drug classes may in fact be targeting the same pathway, and may have a similar mechanism of action, which may be why the outcomes in terms of progression-free survival were so similar”, said David Nanus (Weill Cornell Medical College, New York, NY, USA). “But the most important lesson from this study is that everolimus has less toxicity and similar benefit to VEGFR TKIs in this patient population, who need to be treated repeatedly”, Nanus said.
Published Online May 4, 2012 DOI:10.1016/S14702045(12)70203-6 For the RECORD-1 subgroup analysis see Br J Cancer 2012; 106: 1475–80
Vicki Brower e235