The addition of cetuximab injection to high-dose radiation therapy increased the duration of survival and locoregional control in patients with locally advanced squamous cell carcinoma of the head and neck. Adverse events associated with treatment were in line with previous clinical experience of cetuximab and radiotherapy. The results of this international, randomised, phase III study are being presented at the world’s largest annual clinical oncology meeting, the American Society of Clinical Oncology (ASCO) 40^th Annual Meeting, and are considered to be important enough that the companies who market cetuximab plan to discuss these findings and other head and neck cancer clinical data with the European Medicines Agency (EMEA) and the US Food and Drug Administration (FDA).

Cetuximab is not currently approved for use in the UK ; however EU approval for the use of cetuximab in combination with irinotecan in patients with EGFR- expressing metastatic colorectal cancer who have failed previous irinotecan therapy is anticipated in June 2004.

The percentage of patients alive at two and three years post-treatment was 62% and 57% for cetuximab-treated patients compared with 55% and 44% for those treated with radiotherapy alone. Likewise, the percentage of patients who achieved locoregional control at one year and two years following treatment was 69% and 56% in cetuximab-treated patients compared with 59% and 48% for those treated with radiotherapy alone. Both the difference in duration of survival and the difference in locoregional control were statistically significant (log-rank P = 0.02 for both endpoints).

With a minimum follow-up of 24 months and a median follow-up of 38 months, the median overall survival for the cetuximab-treated patients was 54 months (95% confidence intervals: 36-58) compared with 28 months (95% CI: 21-38) for patients treated with radiotherapy alone.

The incidence of grade 3/4 mucositis (inflammation of the mucous membrane), a serious adverse event associated with high-dose radiation therapy for head and neck cancer, was similar in both treatment groups (55 percent in patients receiving cetuximab and radiotherapy and 52 percent in those who received radiotherapy alone). Three percent of patients in the cetuximab and radiotherapy group experienced grade 3/4 infusion reactions, and grade 3/4 skin reaction occurred in 34 percent of patients receiving radiotherapy plus cetuximab compared with 18 percent of radiotherapy alone patients.

In this phase III trial (IMCL-9815), the impact of combining cetuximab with high-dose radiotherapy on locoregional disease control and overall survival was examined in 424 patients with advanced squamous cell carcinoma of the oropharynx (area of the throat at the back of the mouth), larynx (voice box) or hypopharynx (cavity at the back of the mouth that opens into the oesophagus) that has spread through the head and neck region. Patients were randomised to receive weekly cetuximab therapy in addition to high dose radiotherapy (n=211) or high dose radiotherapy alone (n=213) for six to seven weeks.

  29 April, 2004
NICE guidance supports the use of Lamictal> (tm)>  (lamotrigine) for children

The National Institute for Clinical Excellence (NICE) highlights the impact of epilepsy on children with the publication of guidance following a review of  newer drugs for epilepsy in children1. This follows previous NICE guidance for the treatment of adults with epilepsy, which was published last month. GlaxoSmithKline, manufacturers of Lamictal, a well-established treatment in the newer drugs category, welcomes both sets of guidance as a green light for the NHS to use the newer drugs in treating epilepsy.

The NICE guidance recognises important limitations relating to the older treatments, carbamazepine and sodium valproate, and recommends that the newer antiepileptic drugs (AEDs) be used for the management of epilepsy in children who have not benefited from treatment with the older AEDs, or where the older treatments are unsuitable because:
*       There are contraindications to the drugs
*       They could interact with other drugs the child is taking (notably oral contraceptives)
*       They are already known to be poorly tolerated by the child
*       The child is currently of childbearing potential or is likely to need treatment into her childbearing years

Estimates suggest that there are between 4,000 and 14,000 new consultations for children, aged 0 - 14 years, with epilepsy in the UK each year1. However NICE acknowledges that epilepsy in children differs from adults for various reasons:
*       There are more epilepsy syndromes and causes of epilepsy in children
*       Epilepsy may change with age, with one syndrome evolving into another
*       There is greater potential for impact on social, educational and behavioural aspects of a child> '> s life

The guidance also highlights the impact of epilepsy on a child> '> s development, and draws attention to the implications of potential adverse effects of epilepsy treatments in childhood, which may include influences on behaviour and cognitive function and the impact these factors can have on learning and development.

Lamictal is licensed as monotherapy and add-on therapy in adults and children over 12 years for the treatment of simple and complex partial seizures and primary and secondary generalised tonic-clonic seizures. It is also licensed as add-on therapy in children over 2 years for the treatment of simple and complex partial seizures and primary and secondary generalised tonic-clonic seizures, as well as seizures associated with Lennox-Gastaut syndrome.>

It has been shown that Lamictal does not impair cognitive function2,3, an important consideration in the treatment of children as highlighted by the NICE guidance. Furthermore, Lamictal does not cause weight gain or cosmetic side effects4-6.

The guidance also recognises the significant implications that early treatment decisions may have for later life and states that other important considerations should be discussed with girls with epilepsy and/or their carers1:
*       The risk of AEDs causing harm to an unborn child
*       The possibility of interaction with oral contraceptives

Of all the newer AEDs considered by NICE, Lamictal is one of only three that are licensed in both monotherapy (for adults and children over the age of 12 years) and add-on therapy (for adults and children over 2 years), and Lamictal is the only treatment of these three that does not impair the efficacy of the oral contraceptive pill.  Furthermore the most recent data investigating the relative risks of major congenital malformations with AEDs shows that the risk of these malformations is significantly lower with Lamictal and carbamazepine than sodium valproate7.

Notes 

1.      Lamotrigine has a wealth of clinical experience gained from use in 5 million patients worldwide.

References:

1.      National Institute of Clinical Excellence. Newer Drugs for Epilepsy in Children. 28th April 2004 ,

2.      Gillham R, Baker G, Thompson P, et al. Standardisation of a self-report questionnaire for use in evaluating cognitive, affective and behavioural side-effects of anti-epileptic drug treatments. Epil Res 1996; 24: 47-55.

3.      Gillham R, Kane K, Bryant-Comstock L, Brodie MJ. A double-blind comparison of lamotrigine and carbamazepine in newly diagnosed epilepsy with health-related quality of life as an outcome measure. Seizure 2000; 9: 375-379.

4.      Lamotrigine SmPC.

5.      Patsalos PN, Sander JWAS. Newer antiepileptic drugs - towards an improved risk:benefit ratio. Drug Safety 1994; 11(1): 37-67.

6.      Fitton A, Goa KL. Lamotrigine - an update of its pharmacology and therapeutic use in epilepsy. Drugs 1995; 50(4): 691-713.

7.      Morrow J et al. Which antiepileptic drugs are safest in pregnancy? Preliminary results from the UK epilepsy and pregnancy register.  Epilepsia 2003; 44 (Suppl 8): P096.

22 March 2004
CHALLENGING THE STANDARD FOR GOUT TREATMENT
New Study CONFIRMS THAT ARCOXIA® Provides Equal Pain Relief TO Indomethacin, with fewer SIDE EFFECTS

Newly published results from the largest clinical study of its kind1 confirm that pain relief with ARCOXIA® (etoricoxib) 120 mg once daily is as powerful as that with indomethacin (50 mg three times daily), but with significantly fewer drug-related adverse events, in patients with acute gout. Indomethacin has been regarded as the standard therapy for acute gout2 and considered the most potent non-steroidal anti-inflammatory (NSAID) for the treatment of this condition1.

Sometimes called the disease of Kings and the King of diseases3, gout is the most common form of inflammatory joint disease in men over the age of 402. About one percent of the UK population currently suffers from gout (1.5% of men and 0.4% of women)4 but there has been a steady increase in numbers in the last ten years and over half a million people with gout visited their doctor in 20035.

The randomised, double-blind study evaluated the efficacy and safety of ARCOXIA compared with indomethacin in the treatment of acute gout over an eight-day period. A total of 189 patients with clinically diagnosed acute gout were randomly assigned to receive either ARCOXIA 120 mg once daily (n=103) or indomethacin 50 mg three times daily (n=86). The primary endpoint of the study was the mean change from baseline in patient assessment of joint pain1.

ARCOXIA 120 mg demonstrated clinical efficacy comparable to indomethacin 150 mg in terms of patient assessment of joint pain. The difference between the two treatments in mean change from baseline over days 2 to 5 was -0.08 (95% confidence interval -0.29, 0.13, p=0.46), which fell within pre-specified comparability bounds of -0.5 to 0.5. Comparable efficacy was also confirmed in the secondary endpoints, including onset of efficacy, reduction in signs of inflammation, and patient and investigator global assessment of response to therapy. ARCOXIA patients had a numerically lower incidence of adverse events (43.7%) than indomethacin patients (57.0%), and a significantly lower incidence of drug-related adverse events (16.5% vs. 37.2%; p=0.002)1.

The results from this study reinforce findings from an earlier paper published in the British Medical Journal2. These are the largest studies ever conducted in patients with gout, and the first to demonstrate the efficacy of a selective COX-2 inhibitor in this excruciatingly painful condition1,2 – pain described as so unbearable that sufferers cannot bear the weight of bedclothes on the affected area3. ARCOXIA is the only COX-2 selective inhibitor to be licensed in the UK for the treatment of acute gout6.

The powerful effect of ARCOXIA has also been studied in a broad range of chronic and acute conditions, including osteoarthritis7 and rheumatoid arthritis8. Most recently results have been published demonstrating that in the treatment of osteoarthritis, ARCOXIA 60mg once daily is as effective as the maximum recommended daily dose of diclofenac (50mg three times daily). This study also demonstrated that ARCOXIA 60mg has an earlier onset of action than diclofenac, with significantly more patients experiencing benefit within four hours of taking the first dose (P=0.007)7 .

Notes

ARCOXIA is a powerful NSAID, which works by selectively inhibiting cyclooxygenase-2 (COX-2), the enzyme responsible for pain and inflammation.

Levitra(tm) (vardenafil) Shown To Have Rapid Onset & To Have Success Rates For Twice as Long as Previously Confirme
* Almost two thirds of men (52-64%) with erectile dysfunction on Levitra were able to initiate successful intercourse within just 15 minutes of taking the tablet - compared to placebo over the range of doses 1. According to clinical trial results announced last week.

* Success rates increased even further for all doses (up to 86% compared to placebo) at every measured time interval from 15 minutes to 12 hours after dosing1.

* In a second study, Levitra's reliability in nearly 90% of patients was demonstrated over a two year period. 2 Previous study results have also shown that 77% of men taking Levitra are able to have successful intercourse at the very first attempt 3

Fast Acting - Study Details
In a pooled analysis of two pivotal randomised, double-blind Phase III studies, men who have suffered with ED for more than six months were randomised to receive Levitra 5mg, 10mg or 20 mg or placebo for 12 or 26 weeks.1 Results showed that Levitra statistically improved SEP3 ** success rates at every measured time interval compared with placebo, from the <15-minute interval (success rate of 52-64% for all three doses in those who made attempts) through the >8-<12-hour interval (success rate of 64-86% for all three doses in those who made attempts) from time of dosage.1

Reliable over two years - Study Details

In a one-year extension of a 52-week, double-blind, multicentre study, 566 men agreed to continue receiving Levitra 10 mg or 20 mg for an additional 52 weeks. Of the 479 patients who went on to complete the overall two-year study, results showed:2

* 9 in 10 study participants who took Levitra reported improved erectile function throughout the study period (92% of men taking Levitra 20 mg and 90% of men taking Levitra 10 mg).2

* Previous study results reported participants were five times more likely, on average, to maintain their erection through completion of sexual intercourse (SEP3**) compared to baseline (89% vs 17% for men taking Levitra 20 mg and 87% vs 16% for men taking Levitra 10mg). 4

In all the above studies, the most common adverse events were generally mild to moderate and included headache, flushing, rhinitis and dyspepsia.1,2,4