Clinical Pharmacy News summary

International cancer trials update Results from three major trials showing the value of chemotherapy after surgery and the use of docetaxol as an alternative to paclitaxel in treating ovarian cancer were presented at this year’s annual meeting of the American Society of Clinical Oncology, held in San Francisco last month. The trials recruited patients from the United Kingdom...[more]

NICE guidance on lung cancer issued The National Institute for Clinical Excellence has issued guidance on the use of gemcitabine (Gemzar), paclitaxel (Taxol), docetaxel (Taxotere) and vinorelbine (Navelbine) for treating lung cancer in England and Wales...[more]

NICE guidance on induction of labour issued ...[more]

Cure for baldness remains distant Dutasteride, the drug hailed as a “cure for baldness” in recent national newspaper reports, is still in the early stages of development, according to GlaxoSmithKline, the company developing the drug...[more]

Infliximab “turns off” T cells in psoriasis Infliximab, a tumour necrosis factor-a (TNF-a) antibody, is beneficial in the treatment of moderate to severe plaque psoriasis, a new study shows. Response time is also more rapid compared with that for patients receiving placebo...[more]

Extend therapy for vaginal thrush Recurrent vaginal thrush should be treated with longer courses of antifungal therapy, researchers say...[more]

Anti-TNF drugs not properly funded Over 80 per cent of consultants cannot get proper funding for anti-TNF (tumour necrosis factor) drugs, according to a survey of rheumatologists in the United Kingdom...[more]

Weight loss induced by orlistat reduces other medication Weight loss resulting from the treatment of obesity with orlistat leads to patients having their medicines for hypertension, diabetes and high cholesterol reduced or stopped, according to results of a new study...[more]

International cancer trials update

Results from three major trials showing the value of chemotherapy after surgery and the use of docetaxol as an alternative to paclitaxel in treating ovarian cancer were presented at this year’s annual meeting of the American Society of Clinical Oncology, held in San Francisco last month. The trials recruited patients from the United Kingdom.

The ICON-1 (International Collaboration on Ovarian Neoplasms) and ACTION (Adjuvant Treatment in Ovarian Neoplasms) trials both sought to answer the question of whether cytotoxic chemotherapy is of value after surgery for patients with very small, localised ovarian tumours (FIGO stage I-IIa). Both studies were of a similar design: patients were randomised to platinum-based chemotherapy (with a high degree of investigator discretion in the choice of regimen) or no treatment following surgery. Both studies showed a clear advantage, in terms of disease-free survival, to patients who received chemotherapy. In a combined analysis of 925 patients, disease-free survival five years after randomisation was increased from 65 per cent to 76 per cent by chemotherapy.

These trials also showed a trend towards improved overall survival for chemotherapy recipients, although this only reached statistical significance in ICON-1, where five year overall survival was increased from 75 per cent to 82 per cent (P=0.01) by cytotoxic treatment.

Chemotherapy appeared to be of no benefit to those patients for whom sufficient pathological evidence had been available to assign their disease stage unequivocally. Dr Ignace Vergote, University Hospitals, Leuven, Belgium, who presented the data, suggested that the true value of chemotherapy may be to those with bulkier disease (larger tumours) than that suggested by their staging within the trial.

In another presentation, Dr Paul Vasey of the SCOTROC (Scottish randomised trial in ovarian cancer) group said that docetaxel may represent an alternative to paclitaxel in the combination treatment of advanced ovarian cancer.

The combination of paclitaxel and a platinum complex (usually carboplatin) is the internationally accepted standard of chemotherapy for the treatment of advanced ovarian cancer.

In an attempt to improve on this regimen, the SCOTROC group compared the standard regimen (PC) of paclitaxel (175mg/m2) plus a standard dose of carboplatin every three weeks for six cycles with a similar regimen (DC) in which docetaxel (75mg/m2) was substituted for paclitaxel. The investigators hoped that the new combination would prove more potent than the original — it was powered to detect 25 per cent superiority in either arm — and produce less neurotoxicity. In fact, in terms of efficacy, both regimens appear to be identical. Response rates were 76 per cent and 75 per cent for PC and DC, respectively, and one-year progression-free survival (assessed after a median follow-up of eight months) was identical for the two study groups.

Although DC did produce less neurotoxicity than PC during and after treatment, it was more myelotoxic, and resulted in more febrile neutropenia and a greater requirement for use of granulocyte-colony stimulating factor to maintain patients’ white blood cell counts.

All of the abstracts for the ASCO meeting and many of the full presentations are available on the ASCO website (www.asco.org).
— Contributed by Maxwell Summerhayes.

Forum p833

Back to Top

NICE guidance on lung cancer issued

The National Institute for Clinical Excellence has issued guidance on the use of gemcitabine (Gemzar), paclitaxel (Taxol), docetaxel (Taxotere) and vinorelbine (Navelbine) for treating lung cancer in England and Wales.

The NICE recommends that the use of these drugs should be considered as an option for patients who are not suitable for, or who are unlikely to respond to, potentially curative treatment. They should also be considered as part of the first-line treatment of patients with advanced non-small cell lung cancer. The NICE advises that the most effective form of treatment is likely to be any one of these drugs in combination with platinum-based chemotherapy.

A recommendation that docetaxel should be considered as monotherapy for treating patients whose cancer is locally advanced or has metastasised has also been made. However, the NICE says that the recommendation should only be considered if the patient has suffered a relapse after receiving initial chemotherapy with other agents. Estimations of how many patients currently receive chemotherapy for lung cancer vary between 1,320 and 5,280 per year. The NICE adds that if these patients switch to a combination of a platinum-based chemotherapy together with one or more of the four drugs there would be an increase in National Health Service spending of between £3.8m and £15.3m per year.

The NICE also points out that, because these drugs cause fewer side effects than older chemotherapeutic agents, their use is likely to increase with time. This, it says, will increase costs but might allow more care to be provided in outpatient rather than in inpatient settings.

Copies of the full guidance are available on the NICE website (www.nice.org.uk).

Back to Top

NICE guidance on induction of labour issued

The NICE has issued a national guideline on the induction of labour. The guideline is a summary of a full guideline published by the Royal College of Obstetricians and Gynaecologists and provides evidence-based recommendations for the induction of labour, including the use of prostaglandins and oxytocin. The full guideline is available on the RCOG website (www.rcog.org.uk) and the NICE’s summary on the NICE website (www.nice.org.uk).

Back to Top

Cure for baldness remains distant

Dutasteride, the drug hailed as a “cure for baldness” in recent national newspaper reports, is still in the early stages of development, according to GlaxoSmithKline, the company developing the drug.

A spokeswoman for the company told The Journal this week that dutasteride (GI198745) was currently in phase II trials. “If it continues to show promise within clinical trials it might reach the market in two to five years. However, this is only a general prediction,” she said.

Dutasteride is a dual 5-alpha reductase inhibitor that inhibits type I and type II 5-alpha reductases. It is being developed as a treatment for both benign prostatic hyperplasia and alopoecia.

Dutasteride works by blocking the peripheral conversion of testosterone to dihydrotestosterone, which, at increased levels, causes the miniaturisation of hair follicles seen in male pattern hair loss.

Dutasteride is in a similar class of drug to Merck Sharp & Dohme’s finasteride (Propecia), although finasteride inhibits only type II 5-alpha reductase (PJ, October 30, 1999, p701).

Back to Top

Infliximab “turns off” T cells in psoriasis

Infliximab, a tumour necrosis factor-a (TNF-a) antibody, is beneficial in the treatment of moderate to severe plaque psoriasis, a new study shows. Response time is also more rapid compared with that for patients receiving placebo.

Dr U. Chaudhari from the UMDNJ-Robert Wood Johnson Medical School, New Jersey, United States, and colleagues, say that the results of their study prove that TNF-a, among other cytokines and growth factors that are over-expressed in psoriatic plaques, has a role in the pathogenesis of psoriasis. Infliximab can inactivate TNF-a that is soluble, expressed on the cell surface, or that is associated with the TNF receptor. Therefore it could have the ability to turn off already activated T cells in visible psoriatic plaques, they say.

The researchers randomly assigned 33 patients aged between 21 and 69 years, who had a history of plaque psoriasis for a minimum of six months and a history of topical corticosteroid failure, to receive either intravenous placebo, infliximab 5mg/kg or infliximab 10mg/kg. Patients were given treatment at zero, two and six weeks and were assessed at week 10. An overall clinical evaluation of the quality and extent of plaques relative to baseline was measured using the Physician’s Global Assessment (PGA).

Nine out of 11 patients in the infliximab 5mg/kg group and 10 out of 11 patients in the infliximab 10mg/kg group achieved a good, excellent or clear rating on the PGA, compared with two out of 11 patients in the placebo group. One patient in each treatment group withdrew from the study. The researchers found that in both infliximab treatment groups, the median time to response was four weeks.

The authors say that the treatments currently available for moderate to severe psoriasis have either low efficacy in some patients or are associated with toxic effects. However, in their study infliximab was well tolerated. The study is published in The Lancet (2001;357:1842).

A spokeswoman for Schering-Plough told The Journal on June 12 that a licence for the use of infliximab for the treatment of psoriasis in the UK, was not imminent but was being considered. She added that the data so far were too limited.

Back to Top

Extend therapy for vaginal thrush

Recurrent vaginal thrush should be treated with longer courses of antifungal therapy, researchers say.

Dr S. El-Din, mycology reference centre, University of Leeds, and colleagues investigated whether recurrent episodes of vulvo-vaginal candidiasis occurred as a result of vaginal relapse (caused by incomplete yeast eradication) or reinfection.

Vaginal swabs were taken at an initial clinic visit and then after four and 12 weeks. Women were treated with a single 500mg clotrimazole pessary and 47 women completed the study. Of these, 13 had one-off positive results for candidiasis infection, 12 had positive results at a second visit, despite therapy, and 22 had recurrent infection (with negative results between infections). Of the 22 women, the same strain was responsible for the initial and recurrent infection in 17 cases.

The researchers say that their findings support the vaginal relapse hypothesis.They note that since antifungal resistance does not appear to be a problem in the general population, prolonged courses of antifungals may be appropriate for women with recurrent vaginal thrush. One approach that they suggest is to extend courses of oral antifungals followed by regular prophylaxis, once or twice monthly, with either vaginal pessaries or systemic therapies.

The study is published in Sexually Transmitted Infections (2001;77:179).

Back to Top

Anti-TNF drugs not properly funded

Over 80 per cent of consultants cannot get proper funding for anti-TNF (tumour necrosis factor) drugs, according to a survey of rheumatologists in the United Kingdom.

The survey was conducted by the British Society for Rheumatology (BSR). It showed that 53 per cent of the consultants who responded said they could not get any funding from health authorities for this class of drug, with a further 28 per cent saying they had some funding but not enough. Dr Andrew Bamji of the BSR, said in a press release on May 18: “These treatments are, literally, a life-line for those in whom other treatments have failed. But many people are being denied the drugs because health authorities are simply refusing to fund them.”

The National Institute for Clinical Excellence is expected to issue guidance on the use of the anti-TNF agents etanercept and infliximab in October.

Back to Top

Weight loss induced by orlistat reduces other medication

Weight loss resulting from the treatment of obesity with orlistat leads to patients having their medicines for hypertension, diabetes and high cholesterol reduced or stopped, according to results of a new study.

Professor Alfred Wirth, of Teutoburger Wald Clinic in Bad Roghenfelde, Germany, conducted a practice-based study involving 15,549 obese patients treated with orlistat (recommended therapy was 120mg three times a day combined with a reduced fat diet for six to nine months). The average weight loss after seven months treatment was 10.7 per cent (P<0.0001 versus baseline) of total body weight.

Of the patients with dyslipidaemia, 46 per cent had their cholesterol lowering medication reduced or stopped during the study. In addition, a third of those with type 2 diabetes (34 per cent) and one quarter of those with high blood pressure (26 per cent) had the medication for their other conditions reduced or stopped. The results were presented at the 11th European Congress on Obesity in Vienna, Austria, last week.

Results of another study presented at the congress showed that liquid meal-replacement diets were more effective than conventional low-calorie diets in terms of calorie restriction and weight loss.

Dr Herwig Ditschuneit, of the University of Ulm in Germany, conducted a trial involving 100 obese patients. Half of the patients were asked to limit their calorie intake to between 1,200 and 1,500 calories a day by eating less and choosing low-fat foods. The other half were asked to replace two of their daily meals with a diet drink containing 220 calories and have a dinner of up to 900 calories.

After three months, patients on the diet that included liquid meal replacements had lost, on average, 7.1kg (standard deviation ±3.5kg), whereas those on a traditional low calorie diet lost an average 1.3kg (±2.2kg). The study was continued for four years with all patients being asked to limit their calorie intake to 1,500 calories a day with one meal replaced by a diet drink. The weight loss achieved in the first part of the study was maintained by 56 per cent of patients.

A review of drug treatments for obesity is published in the BMJ (2001;322:1406).

Back to Top