Biomedical subjects

H M Bryson

Publications and source records attributed to H M Bryson.

41 records · Page 3Linked to original sources

PubMed1993

Cladribine. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in haematological malignancies.

Cladribine (2-chloro-2'-deoxyadenosine) is an adenosine deaminase-resistant analogue of deoxyadenosine. In the treatment of hairy cell leukaemia, cladribine has demonstrated excellent efficacy (complete response in 33 to 92% of patients) in noncomparative studies. Cladribine appears to compare favourably with other systemic agents in this indication as it achieves a high degree of efficacy after a single 7-day course, with an acceptable tolerability profile. However, long term data and direct comparative studies with interferon-alpha and pentostatin (deoxycoformycin) are required to confirm the finite advantages offered by cladribine. Preliminary results obtained in other indications including chronic lymphocytic leukaemia, non-Hodgkin's lymphoma, cutaneous T cell lymphoma, Waldenström's macroglobinaemia and acute myeloid leukaemia in children have been sufficiently encouraging to warrant further study. Early pharmacokinetic data suggest that cladribine may be administered by oral and subcutaneous routes, both of which permit convenient outpatient therapy. Myelosuppression, the dose-limiting toxicity of cladribine, and culture-negative fever are the most common adverse effects associated with therapy. However, cladribine appears to be only rarely associated with many of the other adverse effects that characterise antineoplastic therapy. In the weeks post-treatment, there is a small but definite risk of serious infection; infections with a fatal outcome have been reported in a number of studies with cladribine. In conclusion, preliminary data concerning cladribine have been extremely encouraging. Should early response rates in patients with hairy cell leukaemia be sustained, the efficacy of the drug, together with a short treatment regimen, a favourable tolerability profile, and the possibility of oral therapy, suggest that cladribine is likely to supersede other agents available for this indication.

Animals↗

PubMed1993

Tamoxifen: a review of pharmacoeconomic and quality-of-life considerations for its use as adjuvant therapy in women with breast cancer.

Extensive clinical experience, summarised in the recent overview of the Early Breast Cancer Trialists' Collaborative Group (EBCTCG), have confirmed that tamoxifen reduces the rate of both disease recurrence and mortality when administered as adjuvant therapy in women with early breast cancer. Tamoxifen is now established as the preferred adjuvant agent in postmenopausal women; in particular, patients with node-positive, estrogen receptor-positive breast cancer have the most to gain from tamoxifen therapy. Data from a decision-analysis model indicated that tamoxifen monotherapy had a cost-utility ration {$US6000 per additional quality-adjusted life-year (QALY), in 1989 dollars} 5 to 6 times lower than that cited as the cost-acceptability cut-off point in the US. While tamoxifen monotherapy is effective in postmenopausal women, the EBCTCG overview findings indicate that a combined regimen of tamoxifen and antineoplastic chemotherapy has superior efficacy in the same patient group. An issue of current interest is whether the added benefit offered by such a regimen can be justified in terms of added toxicity and cost. Data from a decision-analysis model indicate that combined therapy has a high incremental cost-utility ratio ($US58 000 per additional QALY, in 1989 dollars) compared with no therapy in postmenopausal women. However, the quality-of-life measures TWiST (Time Without Symptoms and Toxicity) and Q-TWiST (quality-adjusted TWiST) indicate that the early toxicity associated with a combined regimen appears to be justified given the superior long term benefits. Patient preference data from 1 study further indicate that the degree of benefit offered by a combined regimen would be acceptable to the majority (73%) of patients. Other areas where pharmacoeconomic analyses may help define more closely the optimal use of adjuvant tamoxifen is in patients at low risk of developing metastatic disease and in determining the optimal duration of therapy. Both areas require further clinical data. In conclusion, tamoxifen adjuvant monotherapy has a low cost-utility ratio in postmenopausal women with node-positive, estrogen receptor-positive breast cancer. Combined therapy in the same patient group has a high cost-utility ratio compared with no therapy but quality-of-life and patient preference data suggest that the costs may be justified. Firm conclusions relating to the use of the drug in other patient subgroups and the optimal duration of therapy await further research.

Age Factors↗

PubMed1992

Halofantrine. A review of its antimalarial activity, pharmacokinetic properties and therapeutic potential.

Halofantrine is an orally administered blood schizontocide which is active against both chloroquine-sensitive and chloroquine-resistant plasmodia. Dose-finding and noncomparative clinical trials have confirmed the efficacy of halofantrine in the treatment of falciparum malaria in areas of chloroquine- and sulfonamide/pyrimethamine-resistant malaria and vivax malaria. However, poor results obtained in patients who failed mefloquine prophylaxis suggest that the efficacy of halofantrine may not extend to mefloquine-resistant P. falciparum, although more studies are needed to confirm this. Data concerning halofantrine in the treatment of P. ovale and P. malariae infections are still limited. One comparative study indicates that halofantrine has an efficacy equivalent to that of mefloquine and may be better tolerated. Halofantrine is generally well tolerated in both adults and children, the most common drug-associated effects being abdominal pain, pruritus, vomiting, diarrhoea, headache and rash, although it is difficult to distinguish between disease- and treatment-related events. The development of parasite resistance to halofantrine, like other blood schizontocides, is inevitable. Poor absorption resulting in variable peak plasma halofantrine concentrations, and possible cross-resistance with mefloquine, may accelerate the emergence of resistance to halofantrine. Thus, it is of primary importance that halofantrine is used only in areas where chloroquine- and sulfonamide/pyrimethamine-resistance are established in order to preserve and sustain its efficacy. If used with care, halofantrine will provide an important treatment option for falciparum malaria, a widespread parasitic disease associated with considerable morbidity against which the number of effective drugs available is being increasingly compromised by the spread of resistance.

Animals↗

PubMed1992

Intranasal fluticasone propionate. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in allergic rhinitis.

Fluticasone propionate is a potent topical anti-inflammatory corticosteroid with low systemic activity. Available pharmacodynamic data are only preliminary; however, large placebo- and drug-controlled clinical studies involving almost 4000 patients with seasonal allergic rhinitis and 1500 with perennial allergic and nonallergic rhinitis have confirmed the efficacy of intranasal fluticasone propionate in the control of nasal symptoms. Fluticasone propionate generally demonstrated similar efficacy compared with intranasal beclomethasone dipropionate, flunisolide acetonide and oral astemizole and better or a trend towards better efficacy compared with oral loratadine, terfenadine, cetirizine and intranasal sodium cromoglycate (cromolyn sodium) against nasal symptoms. The incidence of adverse effects in association with intranasal fluticasone propionate appears to be comparable to that observed with placebo; the most frequently reported effects are nasal dryness/burning, epistaxis and headache. Consistent with its minimal systemic availability, intranasal fluticasone propionate in a dosage of up to 4 mg/day does not cause adrenal suppression. Thus, based on early data from large clinical trials, fluticasone propionate administered once daily offers an effective and convenient treatment option in patients with seasonal and perennial allergic rhinitis, and is distinguished by its low oral bioavailability.

Administration, Intranasal↗

PubMed1992

Selegiline: an appraisal of the basis of its pharmacoeconomic and quality-of-life benefits in Parkinson's disease.

Selegiline (deprenyl) is a selective, irreversible cerebral monoamine oxidase type B inhibitor (MAO-B) that is used in the treatment of Parkinson's disease. It has a relatively mild adverse effect profile without risk of the tyramine ('cheese') reaction at normal therapeutic doses. In about half to two-thirds of patients with mild levodopa response fluctuations, selegiline improves overall disability and 'end-of-dose' fluctuations, with a levodopa-sparing effect. Selegiline thus may improve patient quality of life, although formal cost-utility analyses are required to establish the costs of these benefits. Cost-effectiveness studies may help characterise the relative pharmacoeconomic benefits of selegiline and the dopamine agonists, agents which can also be administered as adjuvant therapy at this stage of the disease. There is also evidence to suggest that selegiline may delay the need for levodopa therapy by up to 11 months in patients with early Parkinson's disease, although the relative contribution of neuroprotective and symptomatic effects of selegiline in these patients has yet to be clarified. From a societal perspective, a theoretical analysis indicates that the economic benefits of selegiline therapy are likely to be substantial. An agent which slowed progression of disability by around 10% would realise savings, through reduction in both direct and indirect costs, in the order of $US330 million per annum in the United States. Available data suggest that selegiline slows progression of symptoms well in excess of 10%. Further, if a simple and inexpensive method is developed to identify preclinical Parkinson's disease before nigrostriatal damage is advanced, selegiline may be useful in a broader patient population with possible financial benefits to society through reduction of the considerable indirect costs of Parkinson's disease.

Cost of Illness↗