Prescrire Int [JOURNAL]
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200 papers
Nivolumab (OPDIVOO) BRAF V600 mutation-negative metastatic or inoperable melanoma: survival advantage.
Prescrire Int · 2016 Dec · PMID 30758924
Existing drugs are poorly effective in patients with inoperable or meta- static melanoma without a mutation in the BRAF gene at position V600. The first-line treatment of choice for patients with BRAF V600-positive melan...
Existing drugs are poorly effective in patients with inoperable or meta- static melanoma without a mutation in the BRAF gene at position V600. The first-line treatment of choice for patients with BRAF V600-positive melanoma is a combination of dabrafenib (a BRAF inhibitor) and trametinib. Nivolumab is a human monoclonal antibody designed to block receptors for PD-1 (programmed cell death-1) and thus to enhance T lymphocyte activity, especially against tumour cells. Nivolumab has been authorised in Europe as monotherapy for patients with inoperable or metastatic melanoma, regardless of BRAFV600 status. Nivolumab has not been compared with the dabrafenib + trametinib combination in patients with BRAF V600-positive melanoma. A randomised double-blind trial ver- sus dacarbazine involved 418 patients with inoperable or metastatic BRAF V600-negative melanoma who had not yet received medication for this stage of the disease.The trial was halted prematurely when an unscheduled analysis showed an improvement in one-year survival with nivolumab compared to dacarbazne(73% versus 42%, p<0.0001). A double-blind trial compared first-line treatment with nivolumab, ipili- mumab or a combination of the two drugs.The mortality results are not yet available in mid-2016.The median time to melanoma aggravation or death was 6.9 months in the nivolumab group, 2.9 months in the ipilmumab group, and 11.5 months with the com- bination (p<0.001). A comparative, randomised, unblinded trial included 405 patients with metastatic or inoperable melanoma in whom at least one drug had failed. An interim analysis conducted after about two years showed no stat- istically significant difference in medi- an survival between patients who received nivolumab and those who received cytotoxic drugs. As expected, given its protein structure and mechanism, the adverse effects of nivolumab are mainly due to immunological mechanisms.They are numerous and affect many organs: skin rash and toxic epidermal necrolysis, thyroid dysfunction, hepatitis, pneumonia, colitis and encephalitis. Adverse effects were serious in 9% of patients, and a few cases were fatal. In practice, first-line nivolumab monotherapy was significantly more effective than dacarbazine in a trial in patients with BRAF V600-negative inoperable or metastatic melanoma. Although its evaluation must continue, nivolumab already seems to be a better option than dacarbazine and ipilimumab for treatment-naive patients, provided they receive detailed and balanced information on the uncertainties, efficacy and adverse effects of this new drug. For other patients, there is no evidence that nivolumab monotherapy represents an advantage over other available treatments.
Trametinib (MEKINIST°) Metastatic or inoperable BRAF V600-positive melanoma: a few extra months of life.
Prescrire Int · 2016 Dec · PMID 30758923
About 50% of patients with meta- static or inoperable melanoma carry a tumour with BRAF V600 mutation.The drug of first choice for these patients is vemurafenib, a BRAF inhibitor, which appears to prolong survival by a f...
About 50% of patients with meta- static or inoperable melanoma carry a tumour with BRAF V600 mutation.The drug of first choice for these patients is vemurafenib, a BRAF inhibitor, which appears to prolong survival by a few months. Dabrafenib is a vemurafenib me-too with a slightly different known profile of adverse effects. Trametinib, a MEK inhibitor, is now authorised in the European Union for use in this setting, either as monotherapy or in combination with dabrafenib (marketed by the same company). Trametinib monotherapy has not been compared to BRAF inhibitor monotherapy. In a randomised, unblinded trial versus cytotoxic drugs in 322 patients, the median survival time did not differ statistically between the groups (15.6 versus 11.3 months; p = 0.09), but 65% of patients in the chemotherapy group received trametinib after disease pro- gression, making it more difficult to detect a difference between the groups. In an unblinded randomised controlled trial in 704 patients who had never received treatment for metastatic or inoperable disease, the trametinib + dabrafenib combination prolonged median survival by about 8 months more than vemurafenib. In another double-blind randomised controlled trial in 423 patients, median survival was about 6 months longer with trametinib + dabrafenib than with placebo + dabrafenib. The trametinib+ dabrafenibcombination was poorly effective after BRAF inhibitor failure in non-comparative trials including a few dozen patients in which the only endpoint was tumour response. Trametinib has many adverse effects, some of which can be life-threatening, such as heart failure, deep vein thrombosis, bleeding (including intracranial haemorrhage), neutropenia, and gastrointestinal perforation. Trametinib also causes retinal disorders and pneumonitis. Combining trametinib with dabrafenib reduces the risk of hyperkeratosis and skin cancer associated with dabrafenib, but increases the frequency of fever (including very high fever). Trametinib interactions mainly involve additive effects or antagonism. In practice, when a patient with metastatic or inoperable BRAF V600-positive melanoma is willing to accept the significant toxicity of trametinib in the hope of gaining several extra months of life, the trametinib + dabrafenib combination is a first-line option.
Aflibercept: osteonecrosis of the jaw: Watch out for high-risk situations.
Prescrire Int · 2016 Nov · PMID 30730125
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Aripiprazole: impulse control disorders. Pathological gambling.
Prescrire Int · 2016 Nov · PMID 30730124
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HPV vaccines: too soon to detect an impact on mortality.
Prescrire Int · 2016 Nov · PMID 30730123
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Chronic obstructive pulmonary disease: Useful medications for patients with recurrent symptoms.
Prescrire Int · 2016 Nov · PMID 30715829
Chronic obstructive pulmonary disease (COPD) is a respiratory disorder characterised by largely irreversible changes in air flow due to irritants such as tobacco smoke. Patients with COPD experience acute exacerbations....
Chronic obstructive pulmonary disease (COPD) is a respiratory disorder characterised by largely irreversible changes in air flow due to irritants such as tobacco smoke. Patients with COPD experience acute exacerbations. Severe disease may progress to chronic respiratory failure. We reviewed the literature on basic medications available for COPD, using the standard Prescrire methodology. There are few clinical data on treatment of mild COPD. Regular medication is not necessary for patients who do not have recurrent symptoms. Eliminating exposure to cigarette smoke and other irritants such as workplace irritants, is the only measure known to improve the outcome of COPD. Evaluation of inhaled short-acting beta-2 agonists is based mainly on short-term trials. These drugs have been shown to improve dyspnoea. Salmeterol and formoterol, two long-acting beta-2 agonists, have been extensively evaluated in symptomatic patients. Compared with no treatment, these drugs reduce breathlessness and acute exacerbations, preventing about two hospital admissions per 100 patients with moderate to severe COPD treated for 7 months. Indacaterol and olodateroldo not have a better harm-benefit balance. Inhaled beta-2 agonists occasionally provoke cardiovascular disorders. No excess mortality has been reported among the thousands of COPD patients included in clinical trials. There Is little evidence that ipratropium, an inhaled short-acting anti-muscarinic bronchodilator, improves COPD symptoms. A risk of Increased mortality among COPD patients treated with ipratroplum cannot be ruled out. Tiotroplum, an inhaled long-acting antimuscarinic bronchodilator, has been extensively evaluated In COPD. Tiotroplum has symptomatic efficacy in COPD, reducing dyspnoea and acute exacerbations. Tiotroplum had no tangible advantages over long-acting beta-2 agonists in seven randomised trials including more than 12 000 patients. Glycopyrronium and aclidinium, two other Inhaled long-acting antimuscarinics, do not appear to be more effective. Tiotroplum, like other inhaled anti-muscarinics, has antimuscarinic adverse effects including cardiac, visual and buccal disorders. Glycopyronium may carry a higher risk of serious cardiovascular effects. Combination of an antimuscarinic with an inhaled beta-2 agonist improves symptoms in 7% to 10% of patients. In patients with one or two COPD exacerbations per year, adding an Inhaled corticosterold (beclometa- sone, budesonide or fluticasone) to a long-acting beta-2 agonist prevents about 1 exacerbation during 3 to 4 years of treatment. Inhaled corticosteroids can cause pneumonia, candidiasis, dysphonia and adrenal Insufficiency. Fluticasone seems to have more adverse effects than other inhaled corticosterolds. Theophylline has uncertain efficacy on symptoms of COPD. This drug has a narrow therapeutic index and carries a risk of serious adverse effects. It should not be used in COPD. Long-term treatment with roflumilast or oral corticosteroids has an unfavourable harm-benefit balance in COPD. In practice, in 2016, the first measure in COPD is to eliminate exposure to the irritant, most often tobacco. Drugs used in COPD have only modest, mainly symptomatic efficacy. Treatment should be adapted to symptoms and the frequency of exacerbations: a short-acting beta-2 agonist should be tried first, then replaced by an inhaled long-acting bronchodilator, or possibly tiotropium, when its effect is too short-lived. An inhaled corticosteroid can be added if symptoms persist or exacerbations are frequent.
Opioids: adrenal insufficiency.
Prescrire Int · 2016 Nov · PMID 30715828
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Bevacizumab: vocal cord necrosis. Angiogenesis inhibitors in cancer affect healthy tissues.
Prescrire Int · 2016 Nov · PMID 30715827
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Cervical cancer: screen regularly: maybe vaccinate.
Prescrire Int · 2016 Nov · PMID 30715826
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Guillain-Barré syndrome, in brief.
Prescrire Int · 2016 Nov · PMID 30715825
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Autoimmune diseases and vaccines.
Prescrire Int · 2016 Nov · PMID 30715824
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Human papillomavirus vaccines and Guillain-Barré syndrome: managing uncertainties.
Prescrire Int · 2016 Nov · PMID 30715823
In late 2014, the epidemiological data available on the human papilloma- virus (HPV) 6/11/16/18 vaccine and the HPV 16/18 vaccine, derived from several million vaccinated girls or young women, showed no link between HPV...
In late 2014, the epidemiological data available on the human papilloma- virus (HPV) 6/11/16/18 vaccine and the HPV 16/18 vaccine, derived from several million vaccinated girls or young women, showed no link between HPV vaccination and the development of autoimmune diseases or central or peripheral neurological disorders. A few cohort studies have called these results into question. The detailed results of a large French cohort study focused on 14 types of conditions in girls aged 13 to 16 years, 842 120 of whom received an HPV vaccine. Eleven of these conditions were no more common than in the unvaccinated girls. A statistically significant association was identified between Guillain-Barré syndrome and HPV vaccine: 1 to 2 additional cases per year per 100 000 vaccinees. A link between Guillain-Barr6 syndrome and other vaccines has already been observed, making a causal link plausible, despite the lack of an established causal mechanism. The statistical link between inflammatory bowel disease and HPV vaccines is weak. The statistical association reported in the French study between thyroiditis and the HPV 16/18 vaccine constitutes low-level evidence, but it is consistent with some other weak evidence. As of early 2016, no significant link has been found between thyroiditis and the HPV 6/11/16/18 vaccine. In practice, in view of the uncertainties, healthcare professionals must present the options to girls and their families in a balanced manner. Girls are faced with a choice between a plausible risk of a very rare event (Guillain-Barré syndrome) in the weeks following vaccination, and the risk of a much less rare event (cervical cancer), which is probably reduced by vaccination but occurs many years later. As of early 2016, it is reasonable that some girls will choose to be vaccinated in the hope of reducing their risk of cancer. It is also reasonable that others will choose not to be vaccinated due to the risk of Guillain-Barré syndrome, despite its rarity.
lenalidomide (REVLIMID°) in untreated multiple myeloma.
Prescrire Int · 2016 Nov · PMID 30715822
In an unblended trial in 1623 multiple myeloma patients, treatment with lenalidomide + dexamethasone until disease progression appeared to prolong survival by a few months more than with the thalidomide + melphalan + pre...
In an unblended trial in 1623 multiple myeloma patients, treatment with lenalidomide + dexamethasone until disease progression appeared to prolong survival by a few months more than with the thalidomide + melphalan + prednisone combination given for 18 months, but serious adverse effects were more frequent.
idarucizumab (PRAXBIND°). Don't rely too heavily on this dabigatran antidote.
Prescrire Int · 2016 Nov · PMID 30715821
Dabigatran, an oral anticoagulant that acts by inhibiting thrombin, was first marketed in the European Union in 2008. No antidote has been available, complicating the management of patients who have severe bleeding or re...
Dabigatran, an oral anticoagulant that acts by inhibiting thrombin, was first marketed in the European Union in 2008. No antidote has been available, complicating the management of patients who have severe bleeding or require emergency surgery. In late 2015, idarucizumab, a monoclonal antibody directed against dabigatran, was authorised in the European Union as a specific antidote for dabigatran. It is administered intravenously. In early 2016, most data on the efficacy of idarucizumab come from an interim analysis of a non-comparative trial in 123 dabigatran-treated patients who had serious bleeding or required emergency surgery or invasive procedures. All 123 patients received idarucizumab. Twenty-six patients died, 8 from bleeding. Among the 66 patients with bleeding, the duration of the event could not be determined in 18 cases because the site of bleeding was not visible. Among the other 48 patients, the bleeding stopped in 44 cases after a median of about 10 hours. Fifty-two of the 57 patients who received idarucizumab prior to invasive procedures underwent surgery. The surgeons considered their clotting status to be normal in 48 cases and mildly or moderately abnormal in the other 4 cases. The role of idarucizumab in these outcomes is difficult to assess for several reasons, including: the lack of a comparator; the partly subjective end-points as the use of idarucizumab was known; and failure to take into account the natural rate of dabigatran elimination. Although idarucizumab normalised markers of dabigatran activity in most patients, the clinical impact was not reported in terms of the frequency of bleeding or thrombosis. The EU summary of product characteristics states that a second dose of idarucizumab can be administered in case of marked dabigatran exposure (massive ingestion, severe renal impairment), but this was the case for only two patients included in the clinical trial. Few data on the adverse effects of idarucizumab are available. Idarucizumab carries a risk of hypersensitivity reactions and of developing anti-idarucizumab antibodies, with unknown consequences. In practice, in 2016, close monitoring of patients on dabigatran and standard management of bleeding and its consequences remain the priority. The clinical effects of idarucizumab are poorly documented. Authorisation of this antidote should not lead to trivialising the use of dabigatran. In 2016, warfarin, a vitamin K antagonist, is the standard oral anticoagulant for most patients, despite its inconvenience.
COMMON STEM. -rubicin.
Prescrire Int · 2016 Nov · PMID 30715820
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panobinostat (FARYDAK°). Multiple myeloma: too toxic!
Prescrire Int · 2016 Nov · PMID 30715819
Patients with relapsed or refractory multiple myeloma who have received several lines of therapy have no satisfactory treatment options. High-dose corticosteroid therapy or a combination of low-dose dexamethasone and pom...
Patients with relapsed or refractory multiple myeloma who have received several lines of therapy have no satisfactory treatment options. High-dose corticosteroid therapy or a combination of low-dose dexamethasone and pomaildomide may be proposed. Panobinostat is the first histone deacetylase (HDAC) inhibitor to be authorised in the European Union for use in this indication. A randomised, double-blind, placebo-controlled trial evaluated panobinostat in 768 patients with relapsed or refractory multiple myeloma who were also receiving bortezomib + dexamethasone. Panobinostat did not prolong survival. The median time to myeloma progression, relapse, or death was prolonged by about 3 months with the panobinostat-containing combination, and by a median of about 8 months in the subgroup of patients who had received at least two lines of chemotherapy including bortezomib and an "immunomodulatory" drug. There was no statistically significant increase in survival, however. In this trial, adverse events led one in six patients to discontinue panobinostat and resulted in numerous hospital admissions. The proportion of patients who died from causes unrelated to myeloma was 6.8% in the panobinostat group versus 3.2% In the placebo group. The toxicity of panobinostat affects most vital functions, resulting in a risk of infections as well as haematological, gastrointestinal, cardiac, renal, hepatic and thyroid disorders. These adverse effects are often severe and sometimes fatal. Panobinostat is subject to pharmacokinetic interactions via cytochrome P450 enzymes and P-glycoproteln, and also to pharmacodynamic Interactions. Panobinostat was teratogenic in animal studies. In practice, even when several previous lines of treatment have failed, panobinostatis more toxic than useful In patients with myeloma. It should therefore not be used.
Pesticides: their true costs are wildly underestimated.
Prescrire Int · 2016 Nov · PMID 30715818
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Quinine, cramps and heart failure: deaths. Quinine has an unfavourable harm-benefit balance in the treatment of cramps.
Prescrire Int · 2016 Oct · PMID 30688424
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Idelalisib: deaths from infections. Toxicity and doubtful efficacy.
Prescrire Int · 2016 Oct · PMID 30688423
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Finasteride 1 mg in alopecia: sexual dysfunction, suicidal ideation. Providing balanced information to male patients is key.
Prescrire Int · 2016 Oct · PMID 30688421
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