Prescrire international
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Prescrire international · Apr 2005
Comparative StudyAnastrozole: new indication. Adjuvant treatment of non metastatic breast cancer: useful for some patients.
(1) For postmenopausal women with hormone-receptor-positive breast cancer, the reference adjuvant treatment after surgical excision is tamoxifen (an anti-estrogen), taken orally at a dose of 20 mg/day for 5 years. (2) Anastrozole is the first aromatase inhibitor to be licensed for this use in France. (3) Marketing authorisation was based on the short-term results of a double-blind trial comparing anastrozole (1 mg/day) with tamoxifen (20 mg/day) in 9366 women. The trial is planned to last five years. The results obtained after median follow-up of 4 years showed no difference between the groups in overall survival (109 deaths in each group). ⋯ The following adverse events were statistically less common with anastrozole than with tamoxifen: hot flushes (35.0% versus 40.3%), metrorrhagia, venous thromboembolism (1.1% versus 1.8%), ischaemic stroke (1.1% versus 2.3%), and endometrial cancer (3 versus 15 cases at 4 years). (5) In practice, anastrozole may be beneficial for women who cannot use tamoxifen, such as those at high risk of thrombosis. Anastrozole costs ten times more per day than tamoxifen. Tamoxifen remains the reference adjuvant treatment for all other women.
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Prescrire international · Apr 2005
Stiripentol: new preparation. Severe myoclonic epilepsy of infancy: promising.
(1) Severe myoclonic epilepsy of infancy (Dravet's syndrome) is associated with multiple seizures and progressive onset of mental retardation. Available antiepileptics (valproic acid and clonazepam/clobazam) are only partially effective, even when used in combination. (2) Stiripentol is intended to be added to the valproate + clobazam combination when the latter is ineffective. (3) In a two-month double-blind trial, 9 of 21 infants remained seizure-free when stiripentol was added to the valproate-clobazam combination, whereas all 20 infants receiving a placebo instead of stiripentol continued to have seizures. (4) Two follow-up studies lasting two and three years and involving 37 and 46 children showed that about 20% of patients had a major benefit (fewer seizures) when stiripentol was added to inadequately effective valproate-clobazam combination therapy. ⋯ Stiripentol was only moderately effective in adolescents. (5) Stiripentol has common and sometimes serious adverse effects such as loss of appetite (with ensuing weight loss), drowsiness and insomnia. Stiripentol inhibits several cytochrome P450 isoenzymes, including CYP 3A4, creating a high risk of interactions, especially with co-administered antiepileptics. (6) The stiripentol dose strengths currently available in France are unsuitable for infants weighing less than 10 kg. (7) In practice, given the severity of this type of myoclonic epilepsy of infancy, the addition of stiripentol to ongoing but ineffective valproate-clobazam combination therapy is justified, even though the treatment is somewhat difficult to manage and has not yet been fully evaluated.