Pharmacoeconomic Spotlight on Rotavirus Vaccine RIX4414 (Rotarix™) in Developed Countries

The most common cause of severe diarrhea in infants and young children is rotavirus gastroenteritis (RVGE), which is associated with significant morbidity, healthcare resource use, and direct and indirect costs in industrialized nations. The monovalent rotavirus vaccine RIX4414 (Rotarix™) is administered as a two-dose oral series in infants and has demonstrated protective efficacy against RVGE in clinical trials conducted in developed countries. In addition, various naturalistic studies have demonstrated ‘real-world’ effectiveness after the introduction of widespread rotavirus vaccination programs in the community setting. Numerous cost-effectiveness analyses have been conducted in developed countries in which a universal rotavirus vaccination program using RIX4414 was compared with no universal rotavirus vaccination program. There was a high degree of variability in base-case results across studies even when the studies were conducted in the same country, often reflecting differences in the selection of data sources or assumptions used to populate the models. In addition, results were sensitive to plausible changes in a number of key input parameters. As such, it is not possible to definitively state whether a universal rotavirus vaccination program with RIX4414 is cost effective in developed countries, although results of some analyses in some countries suggest this is the case. In addition, international guidelines advocate universal vaccination of infants and children against rotavirus. It is also difficult to draw conclusions regarding the cost effectiveness of rotavirus vaccine RIX4414 relative to that of the pentavalent rotavirus vaccine, which is administered as a three-dose oral series. Although indirect comparisons in cost-effectiveness analyses indicate that RIX4414 provided more favorable incremental cost-effectiveness ratios when each vaccine was compared with no universal rotavirus vaccination program, results were generally sensitive to vaccine costs. Actual tender prices of a full vaccination course for each vaccine were not known at the time of the analyses and therefore had to be estimated

Mycophenolate Mofetil: A Pharmacoeconomic Review of its Use in Solid Organ Transplantation

Most pharmacoeconomic studies of mycophenolate mofetil have focused on its use as part of maintenance immunosuppression for renal transplantation, involving short-term (3 to 12 months) time frames. In general, mycophenolate mofetil reduced the treatment costs for rejection episodes and graft failure which offset its higher drug acquisition cost compared with azathioprine. Several cost analyses have been modelled on the large multicentre trials of adult renal transplant recipients. The use of mycophenolate mofetil was associated with either cost savings or no additional costs after 6 or 12 months in French, US and Canadian analyses of triple or quadruple immunosuppressant therapy. A further cost analysis utilising a registry database of renal transplant recipients in the US found mycophenolate mofetil to be cost saving compared with azathioprine after 6.4 years when evaluating costs due to graft loss only. Of the limited cost-effectiveness analyses with the drug, one US study modelled the 1- and 10-year cost effectiveness of mycophenolate mofetil and various other immunosuppressants used in combined regimens. Long-term use of mycophenolate mofetil was less cost effective than other regimens, but the use of long-term mycophenolate mofetil in high-risk patients was shown to be a relatively cost-effective strategy. In another US analysis comparing mycophenolate mofetil with azathioprine as part of quadruple therapy, mycophenolate mofetil was associated with slightly lower costs during the first year after renal transplantation as well as improved clinical outcomes. Conclusion: Pharmacoeconomic studies support the use of mycophenolate mofetil as part of immunosuppressant therapy in renal transplantation, at least in the short term. Although the cost effectiveness of mycophenolate mofetil in the long term is less clear, limited pharmacoeconomic data available appear promising. Among issues to be examined in future economic analyses in renal transplantation are the calcineurin-sparing potential of mycophenolate mofetil and the feasibility of using more efficient mycophenolate mofetil dosage regimens when using the drug on a long-term basis. Additional pharmacoeconomic analyses of mycophenolate mofetil are also needed in other types of solid organ transplantation.Cost analysis, Drug evaluations, Immunosuppressants, Mycophenolate mofetil, Pharmacoeconomics, Transplant rejection

Paclitaxel: A Pharmacoeconomic Review of its Use in Non-Small Cell Lung Cancer

A number of first-line chemotherapy options for patients with advanced non-small cell lung cancer (NSCLC) are advocated in treatment guidelines and/or by various clinical investigators. Platinum-based chemotherapy has clearly demonstrated efficacy in patients with advanced NSCLC and is generally recommended as first-line therapy, although there is increasing interest in the use of non-platinum chemotherapy regimens. Among the platinum-based combinations currently used in clinical practice are regimens such as cisplatin or carboplatin combined with paclitaxel, vinorelbine, gemcitabine, docetaxel or irinotecan. The particular combinations employed may vary between institutions and geographical regions. Several pharmacoeconomic analyses have been conducted on paclitaxel in NSCLC and most have focused on its use in combination with cisplatin. In terms of clinical efficacy, paclitaxel-cisplatin combinations achieved significantly higher response rates than teniposide plus cisplatin or etoposide plus cisplatin (previously thought to be among the more effective regimens available) in two large randomised trials. One of these studies showed a survival advantage for paclitaxel plus cisplatin [with or without a granulocyte colony-stimulating factor (G-CSF)] compared with etoposide plus cisplatin. A Canadian cost-effectiveness analysis incorporated data from one of the large randomised comparative trials and showed that the incremental cost per life-year saved for outpatient administration of paclitaxel plus cisplatin versus etoposide plus cisplatin was $US22 181 (30 619 Canadian dollars;$Can) [1997 costs]. A European analysis incorporated data from the other large randomised study and showed slightly higher costs per responder for paclitaxel plus cisplatin than for teniposide plus cisplatin in The Netherlands ($US30 769 vs$US29 592) and Spain ($US19 923 vs$US19 724) but lower costs per responder in Belgium ($US22 852 vs$US25 000) and France ($US28 080 vs$US34 747) [1995/96 costs]. In other cost-effectiveness analyses, paclitaxel plus cisplatin was associated with a cost per life-year saved relative to best supportive care of approximately $US10 000 in a US study (year of costing not reported) or$US11 200 in a Canadian analysis ($Can15 400; 1995 costs). Results were less favourable when combining paclitaxel with carboplatin instead of cisplatin and particularly when G-CSF was added to paclitaxel plus cisplatin. The Canadian study incorporated the concept of extended dominance in a threshold analysis and ranked paclitaxel plus cisplatin first among several comparator regimens (including vinorelbine plus cisplatin) when the threshold level was$Can75 000 ($US54 526) per life-year saved or per quality-adjusted life-year gained (1995 values). Conclusion: Current treatment guidelines for advanced NSCLC recognise paclitaxel-platinum combinations as one of the first-line chemotherapy treatment options. In two large head-to-head comparative clinical trials, paclitaxel plus cisplatin was associated with significantly greater response rates than cisplatin in combination with either teniposide or etoposide, and a survival advantage was shown for paclitaxel plus cisplatin (with or without G-CSF) over etoposide plus cisplatin. There are limitations to the currently available pharmacoeconomic data and further economic analyses of paclitaxel-carboplatin regimens are warranted, as this combination is widely used in NSCLC and appears to have some clinical advantages over paclitaxel plus cisplatin in terms of ease of administration and tolerability profile. Nevertheless, results of various cost-effectiveness studies support the use of paclitaxel-platinum combinations, particularly paclitaxel plus cisplatin, as a first-line chemotherapy treatment option in patients with advanced NSCLC.Antineoplastics, Cost analysis, Drug evaluations, Non small cell lung cancer, Paclitaxel, Pharmacoeconomics

Spotlight on Eptifibatide in Percutaneous Coronary Intervention and Acute Coronary Syndromes

Eptifibatide (Integrilin(R)) is a selective inhibitor of platelet glycoprotein IIb/IIIa receptors used as adjunctive therapy for patients undergoing percutaneous coronary intervention (PCI) and for patients with acute coronary syndromes (ACS), particularly those requiring PCI. Most economic analyses of eptifibatide have incorporated clinical and healthcare resource use data from either the ESPRIT (Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin(R) Therapy) study in low- to moderate-risk patients undergoing selective PCI with stent implantation or the PURSUIT (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin(R) Therapy) trial in patients with ACS. Eptifibatide achieved statistically significant reductions in combined endpoints of death and ischemic complications in both of these large multicenter clinical trials, in which patients were randomized to receive intravenous eptifibatide or placebo as adjunctive therapy to heparin and aspirin (plus a thienopyridine in ESPRIT). In US economic analyses using ESPRIT trial data, approximately 40% and 70% of the acquisition cost of eptifibatide was offset by reduced medical resource consumption during the initial hospitalization period and over a 1-year period, respectively. Eptifibatide was associated with a favorable cost-effectiveness ratio of $US1407 (year 2000 values) per life-year gained (LYG) in a retrospective US cost-effectiveness analysis that incorporated data from the ESPRIT trial and modeled life expectancy using a large cardiovascular database. Several cost-effectiveness analyses used prospectively collected data from the PURSUIT trial and modeled survival projections using similar methods. These analyses, conducted in the US, Canada, and Western Europe, also showed favorable results ($US3761-$US18 In conclusion, significant clinical benefits have been demonstrated with eptifibatide as adjunctive therapy in patients undergoing selective PCI with stent implantation in the ESPRIT trial and in patients with ACS in the PURSUIT trial. Pharmacoeconomic analyses using data from either ESPRIT or PURSUIT have demonstrated favorable cost-effectiveness ratios for both indications in various countries. ESPRIT-based results from the limited number of available economic analyses are particularly favorable. The cost-effectiveness of eptifibatide in ACS (i.e. PURSUIT-based results) may be further improved by targeting the drug for patients in whom catheterisation and PCI are planned, although further analyses are required to confirm this.Acute-coronary-syndromes, Adis-Spotlights, Angioplasty, Eptifibatide

Spotlight on Paclitaxel in Ovarian Cancer The full text of this article was published in PharmacoEconomics 2001; 19 (12): 1227-1259.

Paclitaxel belongs to the group of antitumor agents called the taxanes. Its efficacy in advanced ovarian cancer has been established in large, randomized phase III clinical trials. When used in combination with cisplatin for first-line treatment of advanced ovarian cancer, it is superior to cyclophosphamide/cisplatin, with gains in median survival of around 1 year. Paclitaxel plus carboplatin has similar efficacy to paclitaxel plus cisplatin. There is now consensus that paclitaxel plus either carboplatin or cisplatin is the recommended first-line therapy for patients with advanced ovarian cancer. The particular combination employed may vary between institutions and geographical regions, although paclitaxel plus carboplatin is generally better tolerated (i.e. lower incidence of non-hematologic adverse events) than paclitaxel plus cisplatin and is widely used in many countries. Paclitaxel is also used as monotherapy in second-line (salvage) treatment of ovarian cancer. Pharmacoeconomic analyses performed to date have primarily focused on first-line therapy comparing the combination of paclitaxel/cisplatin with cyclophosphamide/cisplatin. All studies incorporated clinical outcomes data, most commonly from the Gynecologic Oncology Group (GOG) 111 trial, showing a survival advantage for paclitaxel/cisplatin. These studies report incremental cost-effectiveness ratios (ICERs) ranging from $US6395 per additional life-year gained (LYG) in Spain (1995/96 values) to US$44 690 per additional progression-free LYG in France (year of costs not reported). Five studies were based in the US and Canada and these reported very similar ICERs of $US13 135 (year of costs not reported) to$US25 131 (1993 costs) per additional LYG. In all of these studies the incremental costs of paclitaxel/cisplatin therapy fall well within the commonly cited threshold limit of $US50 000 for new therapies and compare well with incremental costs reported for other oncologic and life-saving therapies. Patient preferences and quality of life are important issues due to the short survival of patients with ovarian cancer. Two cost-utility studies reported similar incremental cost-utility ratios (ICURs). In the study based on US costs, the ICUR of paclitaxel/cisplatin treatment was$US18 200 per additional quality-adjusted life-year (QALY) [1995 drug costs]. In a Canadian study the ICUR ranged from 11 600 Canadian dollars ($Can) to$Can24 200 (1996 costs) per additional progression-free QALY depending on the choice of second-line treatment. Conclusions: Paclitaxel used in combination with cisplatin offers survival and utility gains versus cyclophosphamide plus cisplatin, when used as first-line treatment in patients with stage III or IV ovarian cancer. The incremental cost for these gains is within the accepted range for healthcare interventions. However, pharmacoeconomic analyses of paclitaxel plus carboplatin - a combination widely accepted for use in women with advanced ovarian cancer and with clinical advantages over paclitaxel plus cisplatin in terms of ease of administration and tolerability profile - are currently lacking. Nevertheless, results of available pharmacoeconomic data support the clinical use of paclitaxel/platinum combinations, particularly paclitaxel plus cisplatin, as a first-line chemotherapy treatment option in patients with advanced ovarian cancer.Cost analysis, Ovarian cancer, Paclitaxel, Pharmacoeconomics

Piperacillin/Tazobactam in Moderate to Severe Bacterial Infections The full text of this article was published in PharmacoEconomics 2001; 19 (11): 1135-1175.

Piperacillin/tazobactam is a beta-lactam/beta-lactamase inhibitor combination with a broad spectrum of antibacterial activity against most Gram-positive and Gram-negative aerobic bacteria and anaerobic bacteria. Piperacillin/tazobactam is effective and well tolerated in patients with lower respiratory tract infections (LRTI), intra-abdominal infections, skin and soft tissue infections, and febrile neutropenia. In comparative clinical trials against various other antibacterial regimens, piperacillin/tazobactam has shown higher clinical success rates, particularly in the treatment of patients with intra-abdominal infections and febrile neutropenia. Cost analyses of piperacillin/tazobactam have been variable, in part, because of differences in specific costs included. Three US cost analyses found that piperacillin/tazobactam had lower total medical costs than clindamycin plus gentamicin or imipenem/cilastatin in intra-abdominal infections, and ticarcillin/clavulanic acid in community-acquired pneumonia. Piperacillin/tazobactam plus amikacin had lower total costs than ceftazidime plus amikacin in another cost analysis of patients with febrile neutropenic episodes modeled in nine European countries. However, piperacillin/tazobactam plus tobramycin was more costly than ceftazidime plus tobramycin in hospital-acquired pneumonia in a US cost analysis. In cost-effectiveness analyses, all studies of intra-abdominal infections, pneumonia and febrile neutropenic episodes consistently reported lower costs per unit of effectiveness versus comparators. Piperacillin/tazobactam was dominant (greater efficacy and lower costs) versus imipenem/cilastatin in intra-abdominal infections and ceftriaxone, ciprofloxacin or meropenem in pneumonia. Piperacillin/tazobactam plus amikacin was dominant over ceftazidime plus amikacin in the treatment of febrile neutropenic episodes. In a cost-effectiveness analysis of skin and soft tissue infection, piperacillin/tazobactam had lower costs per successfully treated patient than ceftriaxone or cefotaxime, but a slightly higher cost-effectiveness ratio than amoxicillin/clavulanic acid. All cost-effectiveness analyses were based on decision-analytical models. Conclusions: Piperacillin/tazobactam is likely to reduce overall treatment costs of moderate to severe bacterial infections by increasing initial treatment success, thereby reducing the length of hospital stay and the use of additional antibacterials. Piperacillin/tazobactam has shown clinical and economic advantages over standard antibacterial regimens in the treatment of intra-abdominal infections, LRTIs, febrile episodes in patients with neutropenia, and skin and soft tissue infections, although more complete published data are needed to confirm these results. Present data regarding clinical efficacy, bacterial resistance and costs would support the use of piperacillin/tazobactam as an empirical first-line option in moderate to severe bacterial infections.Antibacterials, Bacterial infections, Cost analysis, Cost effectiveness, Tazobactam/piperacillin

Torasemide: A Pharmacoeconomic Review of its Use in Chronic Heart Failure

Torasemide is a loop diuretic used for the treatment of hypertension and for oedema in chronic heart failure (CHF), renal failure and cirrhosis. The efficacy of torasemide in reducing salt and water retention in CHF has been established in double-blind comparative studies against furosemide. Torasemide has been shown to be at least as effective as furosemide in terms of total volume of urine excreted and also has a longer duration of action. The efficacy of torasemide (in terms of improved CHF symptoms and reduced pulmonary congestion, oedema and bodyweight) has been shown in randomised controlled trials and confirmed in large postmarketing studies. In addition, data from postmarketing studies have shown that patients receiving torasemide had significantly reduced hospital admission rates compared with patients receiving furosemide. Pharmacoeconomic assessments of torasemide have focused on its effect in reducing hospitalisation. Hospitalisation costs due to CHF decreased by 86% during the 11.2-month period of torasemide treatment, compared with the 6-month period prior to treatment, in a US retrospective study assessing medical and pharmacy claims data. Overall, average monthly costs for patients decreased by 56.6% after 5.1 months (from $US1897.28 to$US823.70 per patient per month; PPPM), and by 76% after 11.2 months (from $US1944.76 to$US470.76 PPPM) of torasemide treatment. In the furosemide group, average monthly costs for patients increased moderately from $US227.28 to$US261.18 PPPM after 12 months. Direct comparison of the torasemide and furosemide study groups was not possible because the group receiving torasemide had much higher healthcare resource use at baseline. Compared with furosemide, torasemide was associated with reduced rates of hospital admissions for CHF and/or cardiovascular causes in 3 studies, a retrospective analysis conducted in Germany, a prospective US study of patients enrolled from hospital admissions and a decision-analysis model. As a result, the direct costs of treatment for CHF or cardiovascular diseases for patients treated with torasemide were less than those with furosemide. However, in the US study, there was no statistically significant difference in hospital admissions for all causes and/or in overall direct medical costs, although the study was not powered to show this. In another US study of managed care patients with New York Heart Association (NYHA) class II or III CHF, no difference in clinical or economic outcomes was observed between patients taking torasemide or furosemide; despite the higher acquisition costs for torasemide, total costs were similar for both groups. Torasemide was found to be more cost effective than furosemide in terms of cost per patient with improved functional (NYHA) class of CHF severity in a retrospective German analysis, although this measure is not ideal. This study also evaluated indirect costs (for loss of productivity of employed patients) and results suggest torasemide has a favourable effect in reducing days off work compared with furosemide, although the population of employed patients in the study was very small. Torasemide has been shown to improve some measures of quality of life in 2 studies. It was associated with higher quality-of-life scores than furosemide in a 6-month study, but the differences were only significant at month 4. In another study, torasemide significantly improved fatigue, but full study details are yet to be published. Conclusions: Despite the higher acquisition cost of torasemide over furosemide, pharmacoeconomic analyses have shown that torasemide is likely to reduce overall treatment costs of CHF by reducing hospital admissions and readmissions. Torasemide has generally shown clinical and economic advantages over furosemide, although more long term data are needed to confirm these results and to further investigate effects on quality of life. There are limitations to the currently available pharmacoeconomic data, but present data support the use of torasemide as a first-line option for diuretic therapy in patients with CHF presenting with oedema and especially in those patients not achieving relief of symptoms with furosemide.Cost analysis, Drug evaluations, Furosemide, Heart failure, Pharmacoeconomics, Torasemide

Zoledronic Acid: A Pharmacoeconomic Review of its Use in the Management of Bone Metastases

Zoledronic acid (Zometa(R)) is a third-generation nitrogen-containing parenteral bisphosphonate indicated for the treatment of bone metastases due to solid tumours or multiple myeloma and for hypercalcaemia of malignancy (HCM). In patients with advanced breast or prostate cancer, zoledronic acid 4 mg every 3-4 weeks for up to 15 months significantly reduced the proportion of patients with >=1 skeletal-related event (SRE), excluding HCM, compared with placebo. In patients with advanced breast cancer or multiple myeloma, the incidence of SREs was similar in patients treated with zoledronic acid 4 mg or pamidronic acid 90 mg every 3-4 weeks for up to 25 months but, in breast cancer patients, zoledronic acid reduced the risk of SREs, including HCM, by an additional 20% compared with pamidronic acid. In modelled cost-utility studies comparing direct costs based on efficacy and resource-use data from these and/or other trials, results have varied. In the most recent study performed from the perspective of the UK NHS and modelled over a 10-year treatment period in women with advanced breast cancer, intravenous zoledronic acid and oral ibandronic acid were dominant over no treatment. Intravenous zoledronic acid was the most cost effective, in terms of incremental costs per QALY gained, followed by oral ibandronic acid, intravenous pamidronic acid and intravenous ibandronic acid. Two other modelled analyses in patients with advanced breast cancer, also conducted from the perspective of the NHS, evaluated the cost utility of three bisphosphonate therapies in patients receiving hormonal therapy or intravenous chemotherapy. Analyses were modelled over 14.3 months (i.e. expected survival) and assumptions varied markedly from results in clinical breast cancer trials. Also, efficacy assumptions for zoledronic acid were not based on clinical trials with the drug. The results of these analyses suggest that oral ibandronic acid is more cost effective than intravenous zoledronic acid and intravenous pamidronic acid in terms of incremental cost per QALY gained. In a global, 15-month modelled cost-effectiveness analysis of patients with advanced prostate cancer, conducted from a third-party perspective, the incremental cost per QALY gained for zoledronic acid versus no treatment was $US159_200 (year 2000 value), which is about 3-fold greater than commonly accepted thresholds for cost effectiveness. In conclusion, a recent modelled economic analysis suggests that intravenous zoledronic acid 4 mg is dominant relative to no treatment in the management of bone metastases in patients with advanced breast cancer. In contrast, in patients with advanced prostate cancer, the incremental cost per QALY gained for zoledronic acid 4 mg versus no treatment was predicted to be higher than commonly accepted thresholds. Compared with other bisphosphonates in the setting of advanced breast cancer, intravenous zoledronic acid was more cost effective than oral or intravenous ibandronic acid and intravenous pamidronic acid in one study, but less cost effective than oral ibandronic acid in another. Further efficacy and economic data comparing intravenous zoledronic acid with oral ibandronic acid are needed. Meanwhile, zoledronic acid appears to be the most cost effective intravenous bisphosphonate for the management of bone metastases in patients with advanced breast cancer and possibly in patients with different types of advanced solid tumours.Adis-Drug-Evaluations, Bone-cancer, Cancer, Cost-effectiveness, Cost-utility, Zoledronic-acid

Management of Postmenopausal Osteoporosis: Defining the Role of Raloxifene

Postmenopausal osteoporosis is a very common disease, and approximately half of all women aged >50 years will experience an osteoporotic fracture during the remainder of their lifetime. The predominant cause of postmenopausal osteoporosis is the decline in estrogen levels, which causes an increase in bone turnover, and results in a loss of bone mass throughout the entire skeleton. Fragility fractures, either vertebral or nonvertebral, have a considerable adverse effect on quality of life in women with osteoporosis and place a significant burden on society in terms of healthcare costs. Management of postmenopausal osteoporosis includes alteration of modifiable risk factors (e.g. lifestyle and propensity to fall), ensuring adequate calcium and vitamin D intake, and pharmacological treatment to decrease fracture risk by slowing or preventing bone loss and preserving bone strength. Raloxifene (Evista(R)), a selective estrogen receptor modulator that partially mimics the effects of estrogen on bone and lipid metabolism and acts as an antiestrogen in the breast and endometrium, is indicated for the prevention and treatment of postmenopausal osteoporosis. Raloxifene increases bone mineral density at vertebral and nonvertebral sites, and decreases the risk of vertebral fracture to a similar extent to the bisphosphonates alendronate and risedronate. However, effects on nonvertebral fracture risk, including the risk of hip fracture, have not been observed. Raloxifene appears to reduce breast cancer risk (in women at average risk) and cardiovascular risk (in women at increased risk) without stimulating the endometrium, and does not cause vaginal bleeding or breast pain. However, the drug causes hot flashes in some women, and increases the risk of venous thromboembolic events by about the same amount as hormone replacement therapy (HRT). In economic models, raloxifene is cost effective compared with no treatment, HRT, calcitonin, or alendronate for the prevention or treatment of postmenopausal osteoporosis. In conclusion, raloxifene is a valuable and cost-effective therapy for preventing the progression of osteoporosis and for reducing vertebral fracture risk in osteoporotic postmenopausal women. The tendency for raloxifene to cause hot flashes, and its apparent lack of effect on hip fracture risk, may preclude its use in women with vasomotor symptoms and in patients at high risk for hip fracture. Results from large ongoing trials are needed to confirm the effects of raloxifene on breast cancer and cardiovascular disease. However, the effects of raloxifene on breast cancer and cardiovascular risk without stimulating the endometrium make the drug an attractive therapy for the prevention and treatment of postmenopausal osteoporosis.Adis-Drug-Evaluations, Postmenopausal-osteoporosis, Raloxifene

Paclitaxel: A Pharmacoeconomic Review of its Use in the Treatment of Ovarian Cancer

Paclitaxel belongs to the group of antitumour agents called the taxanes. Its efficacy in advanced ovarian cancer has been established in large, randomised phase III clinical trials. When used in combination with cisplatin for first-line treatment of advanced ovarian cancer, it is superior to cyclophosphamide/cisplatin, with gains in median survival of around 1 year. Paclitaxel plus carboplatin has similar efficacy to paclitaxel plus cisplatin. There is now consensus that paclitaxel plus either carboplatin or cisplatin is the recommended first-line therapy for patients with advanced ovarian cancer. The particular combination employed may vary between institutions and geographical regions, although paclitaxel plus carboplatin is generally better tolerated (i.e. lower incidence of non-haematological adverse events) than paclitaxel plus cisplatin and is widely used in many countries. Paclitaxel is also used as monotherapy in second-line (salvage) treatment of ovarian cancer. Pharmacoeconomic analyses performed to date have primarily focused on first-line therapy comparing the combination of paclitaxel/cisplatin with cyclophosphamide/cisplatin. All studies incorporated clinical outcomes data, most commonly from the Gynecologic Oncology Group (GOG) 111 trial, showing a survival advantage for paclitaxel/cisplatin. These studies report incremental cost-effectiveness ratios (ICERs) ranging from $US6395 per additional life-year gained (LYG) in Spain (1995/96 values) to$US44 690 per additional progression-free LYG in France (year of costs not reported). Five studies were based in the US and Canada and these reported very similar ICERs of $US13 135 (year of costs not reported) to$US25 131 (1993 costs) per additional LYG. In all of these studies the incremental costs of paclitaxel/cisplatin therapy fall well within the commonly cited threshold limit of $US50 000 for new therapies and compare well with incremental costs reported for other oncological and life-saving therapies. Patient preferences and quality of life are important issues due to the short survival of patients with advanced ovarian cancer. Two cost-utility studies reported similar incremental cost-utility ratios (ICURs). In the study based on US costs, the ICUR of paclitaxel/cisplatin treatment was$US18 200 per additional quality-adjusted life-year (QALY) [1995 drug costs]. In a Canadian study the ICUR ranged from 11 600 Canadian dollars ($Can) to$Can24 200 (1996 costs) per additional progression-free QALY depending on the choice of second-line treatment. Conclusions: Paclitaxel used in combination with cisplatin offers survival and utility gains versus cyclophosphamide plus cisplatin, when used as first-line treatment in patients with stage III or IV ovarian cancer. The incremental cost for these gains is within the accepted range for healthcare interventions. However, pharmacoeconomic analyses of paclitaxel plus carboplatin - a combination widely accepted for use in women with advanced ovarian cancer and with clinical advantages over paclitaxel plus cisplatin in terms of ease of administration and tolerability profile - are currently lacking. Nevertheless, results of available pharmacoeconomic data support the clinical use of paclitaxel/platinum combinations, particularly paclitaxel plus cisplatin, as a first-line chemotherapy treatment option in patients with advanced ovarian cancer.Antineoplastics, Cost analysis, Ovarian cancer, Paclitaxel, Pharmacoeconomics