Economic and policy implications of adopting paclitaxel as first-line therapy for advanced ovarian cancer: an Ontario perspective

PURPOSE: To determine the potential economic and policy implications that result from incorporating paclitaxel into first-line therapy for stage 3 and 4 ovarian cancer patients in the province of Ontario, Canada. METHODS: A cost-effectiveness analysis was conducted to compare cisplatin/cyclophosphamide (CC), a standard therapy, with cisplatin/paclitaxel (CT). Based on survival curves from a clinical trial, mean costs and survival were calculated. Sensitivity analyses were conducted based on altering the duration of paclitaxel infusion, discount rates, and efficacy of paclitaxel. RESULTS: The mean survival duration is prolonged from 2.06 years with the standard therapy to 2.44 years with the paclitaxel combination. The paclitaxel therapy is more expensive, with a mean cost of $17,469 (Canadian) per patient treated with CT compared with $5,228 per patient with CC. The incremental cost-effectiveness ratio is $32,213 per year gained. Sensitivity analyses show that the conclusions remain unchanged. The use of CT as first-line treatment for advanced ovarian cancer patients in Ontario requires an additional $9 million per year over and above the present costs to treat this patient population. CONCLUSION: Although paclitaxel-based therapy prolongs survival, it comes at an increased cost. It may not be possible to fund paclitaxel treatment using resources presently allocated to first-line chemotherapy for advanced ovarian cancer. The policy implications for absorbing the cost of paclitaxel in the context of a publicly funded health care system are discussed.     

A comparison of the costs of paclitaxel and best supportive care in stage IV non-small-cell lung cancer

PURPOSE: To compare the expenditures associated with single-agent paclitaxel (Taxol) with those of best supportive care as treatment for stage IV non-small-cell lung cancer (NSCLC). METHODS: The primary data sets of 2 phase II trials of paclitaxel in advanced NSCLC were obtained. Paclitaxel delivery costs were estimated at the Ottawa Regional Cancer Centre using the mean paclitaxel dose from the 2 phase II trials, 214 mg/m2, a 3-week schedule and a median of 3 treatment cycles. Data regarding dosage, costs and survival were incorporated into the Statistics Canada POpulation HEalth Model (POHEM), which generated hypothetical cohorts of patients treated either with best supportive care or paclitaxel. The POHEM model assigned diagnostic workup, treatment, disease progression and survival characteristics to each of these cohorts and tabulated the costs associated with each. RESULTS: The total cost of administering 3 cycles of chemotherapy was Can$8143 per patient. The strategy of treating NSCLC patients with paclitaxel cost $3375 more per patient than best supportive care. On the basis of the difference in survival duration between stage IV patients treated in the best supportive care arm of a previous National Cancer Institute of Canada trial and those represented in the pooled phase II survival results, the cost per life-year saved was $4778. For sensitivity analyses, the days of hospitalization for terminal care, number of cycles given and survival benefit produced were varied. The sensitivity analysis produced a cost per life-year saved of up to $21,377 under the least favourable assumptions. CONCLUSION: If large phase III trials confirm the survival benefits observed in the phase II trials, paclitaxel can be considered to be a cost-effective agent in the management of advanced NSCLC.     

The taxoids. Comparative clinical pharmacology and therapeutic potential

Paclitaxel and docetaxel are 2 compounds from the new taxoid class of anti-cancer agents. Both drugs are very similar in preclinical activity, mechanism of action and spectrum of clinical activity. Some subtle differences in the intracellular retention of docetaxel may account for its lack of schedule-related myelosuppression and greater potency, and may be relevant to the skin toxicity and oedema which it produces. Early data suggest that there may be differing behaviour of anthracycline/taxoid combinations with respect to cardiotoxicity. Paclitaxel has been studied in several first-line combination therapy trials in ovarian cancer. Here, paclitaxel in combination with a platinum compound seems to have proven itself as a standard regimen. It is uncertain if docetaxel will be evaluated in this context. An abundance of clinical data is available for both analogues in the advanced, metastatic setting of breast cancer. Both also have been compared as single agents with doxorubicin with the results suggesting paclitaxel in a 3-hour infusion is inferior to the anthracycline (in terms of response rate), and those of docetaxel suggesting it is superior to the same dose of doxorubicin. This indirect comparison favours the activity of docetaxel; however, it is clear that in the dose/schedules studied, the taxoid compounds are not equitoxic. Either agent by itself, in the treatment of metastatic breast cancer, remains appropriate; however, lack of cumulative toxicity may make paclitaxel more attractive in some situations where prolonged administration is foreseen. Lung cancer trials have also confirmed the activity of both agents, although docetaxel appears to have slightly more promising activity in previously treated patients than paclitaxel. Paclitaxel in combination with cisplatin has been evaluated in randomised trials as first-line treatment of non-small-cell lung cancer (NSCLC). The results of these trials taken together suggest that this combination has an impact on survival similar to other new regimens now considered 'standard' in the front-line setting in this disease. Unfortunately, despite all the phase II data generated in numerous tumour types, little else can be said about the role of either taxoid in the 'standard' management of malignant disease. It will be some years yet before taxoid-based combinations have been evaluated sufficiently in randomised trials such that the impact of this novel class can be adequately assessed in terms of survival and cure rates.     

Structural modeling of the pro-ocytocin-neurophysin precursor

This article reviews the information currently available on the pharmacoeconomic profile of taxanes in ovarian cancer. Because paclitaxel is the only taxene approved for this clinical indication, our overview is almost entirely focused on the cost-effectiveness profile of this drug. In advanced ovarian cancer, first-line regimens based on paclitaxel have been reported to be more effective than standard therapy based on cyclophosphamide + cisplatin. The improved survival with paclitaxel and the increased cost induced by this drug have prompted a series of pharmacoeconomic analyses, the results of which are summarized and discussed. Three studies, published between 1996 and 1997, calculated the cost per life-year gained using paclitaxel + cisplatin as opposed to cyclophosphamide + cisplatin. The estimates of survival gain and increased expenditure using paclitaxel were very similar; consequently, the results produced by these three analyses were homogeneous with values of cost per life-year gained around $20000. Because this value is below the conventional limit of $50000, the pharmacoeconomic results on paclitaxel suggest a favorable cost-effectiveness profile. Docetaxel is another taxane proposed for the treatment of advanced ovarian cancer; however, the drug has not yet been approved for this clinical indication and so a pharmacoeconomic assessment on this agent is still premature.     

The cost-effectiveness of routine postoperative radiotherapy after sector resection and axillary dissection for breast cancer stage I. Results from a randomized trial

BACKGROUND: Cost-effectiveness of routine postoperative radiotherapy after breast-conserving surgery has not been prospectively evaluated earlier. In times of rationing of medical resources, valid assessments of cost-effectiveness are important for rational allocation of resources. PURPOSE: Cost and cost-effectiveness of routine postoperative radiotherapy was calculated in a prospective randomized trial comparing sector resection plus axillary dissection with (XRT group) or without (non-XRT group) postoperative radiotherapy in breast cancer stage I. Three hundred eighty-one patients were included. After a median follow-up of five years 43 local recurrences, six of them in the XRT-group occurred (P < 0.0001). No difference in regional and distant recurrence (P = 0.23) or survival (P = 0.44) was observed. PATIENTS AND METHODS: Direct medical costs as well as indirect costs in terms of production lost during the treatment period and travel expenses were estimated from data in the medical records and the national insurance registry of each patient. Average costs of different treatment activities and measures were estimated for the XRT-group and the non-XRT group respectively. From these estimates differences in costs and effectiveness between the groups were calculated and marginal cost-effectiveness ratios were estimated. For the construction of QALYs each life-year was quality-adjusted by a utility value depending on which health state the patient was considered to perceive. RESULTS: Taking into account the cost of primary treatment, the cost of follow-up, the cost of treatment of a local recurrence, travel expenses and indirect costs (production lost) excluding costs for treatment of regional and distant recurrence the cost per avoided local recurrence at five years was SEK 337,727 ($44,438, Pounds 27,018). Adjustment for quality of life showed a cost for every gained QALY to be SEK approximately 1.6 million, ($210,526, Pounds 128,000), range SEK 0.2-3.9 million ($26,315-513,158, Pounds 16,000-312,000). CONCLUSION: The cost of routine postoperative radiotherapy after sector resection and axillary dissection in breast cancer stage I per avoided local recurrence and gained QALY is high. The cost per gained QALY show great variation depending on utility value, which in this study was derived from external observers and not from the patients themselves. These results stress the importance of identifying risk factors for local recurrence, better understanding of impact on quality of life of a local recurrence and adding cost evaluations to clinical trials in early breast cancer.     

Treatments for newly diagnosed advanced ovarian cancer: analysis of survival data and cost-effectiveness evaluation

The main therapeutic options currently available for patients with newly diagnosed advanced ovarian cancer include: (i) cisplatin-based chemotherapy at conventional doses without paclitaxel, (ii) paclitaxel+cisplatin at conventional doses and (iii) high-dose chemotherapy with autologous hematopoietic rescue. After conducting a literature search to identify large-scale clinical trials based on these three therapeutic modalities, we carried out an analysis of the survival data and evaluated the cost-effectiveness ratio where appropriate. Cost data were obtained from published information. Effectiveness was estimated by determining the values of mean lifetime survival (MLS). Our analysis included a total of 15 clinical trials. The values of MLS were 3.05 years per patient for cisplatin-based chemotherapy at conventional doses without paclitaxel (1931 patients), 2.95 years per patient for chemotherapy with paclitaxel+cisplatin at conventional doses (184 patients) and 5.76 years per patient for high-dose chemotherapy with autologous hematopoietic rescue (53 patients). As compared with cisplatin-based chemotherapy without paclitaxel, high-dose treatments with hematopoietic rescue yielded a significantly better survival. Using cisplatin-based chemotherapy as a reference term, the incremental cost-effectiveness ratio for high-dose treatments was $25641 per life year gained (discounted dollars per discounted life year gained). Sensitivity testing suggested that the ratio remained below $50000 under most circumstances. We conclude that in the treatment of patients with advanced ovarian cancer, high-dose chemotherapy with hematopoietic rescue seems to be more effective and more cost-effective than standard treatments with cisplatin-based regimens at conventional doses.     

An economic analysis of alternatives for childhood immunisation against Haemophilus influenzae type b disease

Cost-effectiveness and cost-utility analyses of immunisation strategies against invasive Haemophilus influenzae type b (Hib) disease in Australia were based on a hypothetical birth cohort of 250,000 non-Aboriginal Australian children. The model predicted that, without immunisation, 625 cases of invasive Hib disease would occur in under-five-year-olds, with direct costs of $10.2 million. Universal public sector vaccination beginning before six months of age (6MVAC) prevented 80 per cent of cases; vaccination at 12 months (12MVAC) 62 per cent and at 18 months (18MVAC) 46 per cent. At a vaccine cost of $15 per dose, 18MVAC gave the lowest cost per quality-adjusted life year (QALY) over a wide range of model assumptions, with 6MVAC the 'best' alternative. The best estimate ($ per QALY) for 6MVAC was $6930 (three doses), for 12MVAC $9136 (two doses) and for 18MVAC $1231 (one dose). The cost per QALY of single dose catch-up immunisation of older children was estimated at $8630 at two years, $27,000 at three years and $117,000 at four years if done at a scheduled visit; these values were increased if an additional medical visit was included. The threshold cost per vaccine dose at which an immunisation program became cost-saving was estimated for 6MVAC, 12MVAC and 18MVAC as $11, $10 and $14. Even under a worst-case scenario, an immunisation program at 6, 12 or 18 months became cost-saving if indirect costs of death were included. Comparison with previous analyses revealed the importance of the incidence and age distribution of disability and assumptions about vaccine administration costs in determining model outcomes.     

A possible association between paternal longevity and major depression among elderly men

Platinum-based chemotherapy is the standard treatment for advanced ovarian cancer, with response rates of 40-60%. In patients who fail platinum treatment, paclitaxel has resulted in response rates of 10-48%. Docetaxel has partial non-cross-resistance with and is twice as potent in vitro as paclitaxel in inhibiting microtubule disaggregation. The combination of docetaxel and cyclophosphamide is synergistic in pre-clinical studies and clinically active in breast cancer. We present the case of a patient with platinum and paclitaxel refractory ovarian cancer who achieved a remission with docetaxel and cyclophosphamide.     

Modulation of excision repair cross complementation group 1 (ERCC-1) mRNA expression by pharmacological agents in human ovarian carcinoma cells

CONTEXT: ThinPrep, AutoPap, and Papnet are 3 new technologies that increase the sensitivity and cost of cervical cancer screening. OBJECTIVE: To estimate the cost-effectiveness of these technological enhancements to Papanicolaou (Pap) tests. DESIGN: We estimated the increase in sensitivity from using these technologies by combining results of 8 studies meeting defined criteria. We used published literature and additional sources for cost estimates. To estimate overall cost-effectiveness, we applied a 9-state time-varying transition state model to these data and information about specific populations. SETTING: A hypothetical program serving a cohort of 20- to 65-year-old women who begin screening at the same age and are representative of the US population. RESULTS: The new technologies increased life expectancy by 5 hours to 1.6 days, varying with the technology and the frequency of screening. All 3 technologies also increased the cost per woman screened by $30 to $257 (1996 US dollars). AutoPap dominated ThinPrep in the base case. At each screening interval, AutoPap increased survival at the lowest cost. The cost per year of life saved rose from $7777 with quadrennial screening to $166000 with annual screening. Papnet produced more life-years at a higher cost per year of life saved. However, when used with triennial screening, each of them produced more life-years at lower cost than conventional Pap testing every 2 years. The cost-effectiveness ratio of each technology improved with increases in the prevalence of disease, decreases in the sensitivity of conventional Pap testing, and increases in the improvement in sensitivity produced by the technology. CONCLUSIONS: Technologies to increase the sensitivity of Pap testing are more cost-effective when incorporated into infrequent screening. Increases in sensitivity and decreases in cost may eventually make each technology more cost-effective.     

Quality of life studies of the Australian New Zealand Breast Cancer Trials Group: approaches to missing data

The purpose of this paper is to describe the degree of compliance with quality of life measures in two clinical trials conducted by the Australian New Zealand Breast Cancer Trials Group comparing different chemotherapy policies for metastatic breast cancer. Quality of life was assessed by the patient using linear analogue scales and by the physician using the Spitzer QLI. Compliance was generally good, ranging from 66 per cent to 79 per cent in the earlier study, and from 63 per cent to 97 per cent in the later study. Compliance with physician rated quality of life was consistently slightly better than for patient self-assessment. The results of physician and patient assessments were generally consistent, but there was a systematic bias toward lower quality of life (as assessed by the physician) in patients who failed to comply with self-assessment. Our conclusions were that quality of life can be assessed in large scale multi-institution clinical trials in metastatic breast cancer. The results are important in assessing treatment comparisons. Missing data cannot be assumed to be similar to those available. Optimal assessment of quality of life therefore requires careful prospective attention to complete data collection.     

Paclitaxel (Taxol)

The paclitaxel (TAXOL); Bristol-Myers Squibb Company) represents first agent from novel class of antineoplastic drugs--taxanes to enter routine clinical practice. Paclitaxel interferes with microtubular polymerization by promoting abnormal assembly of microtubules and inhibiting their subsequent disassembly. Pharmacokinetics of paclitaxel has been intensively studied. There are indications for nonlinear pharmacokinetics when paclitaxel is administered as a short infusion and at higher doses. Neurotoxicity, mucositis, and leukopenia correlate with some pharmacokinetic parameters. The clinical development of paclitaxel was initially hampered by hypersensitivity reactions. Current dosage regiments with premedication reduced the incidence of these events to 3%. The major dose-limiting adverse effect of paclitaxel is neutropenia. Significant activities were reported especially in patients with advanced ovarian, breast, non-small cell lung cancer (NSCLC), head and neck cancer and in other types of tumours. Long-term follow-up will also allow the effects of the drug on patient survival to be determined. At present combination of Taxol (paclitaxel) with cisplatin clearly improves the duration of progression-free survival and of overall survival compared with cyclophosphamide and cisplatin in women ovarian cancer. Recently was TAXOL (paclitaxel) registered in Czech republic for treatment of patients with advanced metastatic ovarian carcinoma and in patients with metastatic breast cancer after failure of the standard therapy.     

The female athlete. The triad of disordered eating, amenorrhoea and osteoporosis

The value of routine follow-up programs for patients with early stage breast cancer remains an area of controversy. In recent years, the cost-effectiveness of routine investigations has been questioned, and 2 prospective randomized clinical trials have shown no survival advantage to more intensive diagnostic follow-up approaches. Under the auspices of the Ottawa Regional Cancer Centre, a national survey of the practice patterns of Canadian surgical, radiation and medical oncologists was undertaken to measure current Canadian standards of care and to determine average costs of 5-year follow-up for patients completing primary treatment for stage I and II breast cancer. Standardized questionnaires were sent out to 130 surgeons, 59 radiation oncologists and 89 medical oncologists. The overall response rate was 44%. Based on the frequency of follow-up visits and investigations recommended by respondents, an average cost per patient for a 5-year follow-up plan was derived for each subspecialist group: $791, $911 and $904 for surgeons, radiation oncologists and medical oncologists respectively. Use of a less interventionist follow-up program was estimated to result in a cost saving of $300 per patient over 5 years. The results indicate that, for the most part, Canadian oncologists have been influenced by the available literature concerning follow-up practices and are ordering fewer routine tests. Further cost savings to the Canadian health care system could be achieved with the adoption of even less interventionist follow-up programs.     

Spatial learning and hippocampal volume in male deer mice: relations to age, testosterone and adrenal gland weight

Endoscopic carpal tunnel release is a controversial procedure used in the treatment of carpal tunnel syndrome. Although endoscopic carpal tunnel release is associated with less incisional pain and faster recovery time than the open carpal tunnel release, opponents of endoscopic carpal tunnel release suggest that its benefits are outweighed by its higher complication rates from median nerve transection and transient numbness of the fingers. Because of the huge economic and social impact of carpal tunnel syndrome in this country, we performed a cost-effectiveness analysis comparing endoscopic carpal tunnel release and open carpal tunnel release using guidelines established by the Panel on Cost-Effectiveness in Health and Medicine of the U.S. Public Health Service. A decision analytic model was used to measure differences in cost and effectiveness--expressed as quality-adjusted life-years (QALYs)--between endoscopic carpal tunnel release and open carpal tunnel release. The societal perspective was chosen, and probabilities for various outcomes for the two procedures were obtained from published randomized-controlled trials. Cost data were derived from the Medicare Resource-Based Relative Value Units published in the Federal Register. QALYs were obtained from two groups of health care providers using a utility-assessment questionnaire. Using probabilities for various outcomes from the two published randomized-controlled trials comparing endoscopic carpal tunnel release and open carpal tunnel release, we constructed a decision tree to derive both the cost and the QALYs for the two procedures. The incremental cost difference between endoscopic carpal tunnel release and open carpal tunnel release was $46, using Medicare cost and probabilities of various outcomes derived from a study by Brown et al. in 1993. We calculated QALYs for five age groups--25, 35, 45, 55, 65--assuming a life expectancy of 75 years. The marginal effectiveness (QALY of endoscopic carpal tunnel release minus QALY of open carpal tunnel release) ranged from 0.235 QALY for the 25-year-old age group to 0.066 QALY for the 65-year-old age group, giving a cost-effectiveness ratio of $195/QALY and $693/QALY, respectively. When compared with other accepted medical interventions such as breast cancer screening ($4836/QALY) and exercise to prevent coronary heart disease ($13,508/QALY), endoscopic carpal tunnel release seems to be cost-effective. However, our sensitivity analysis indicated that the cost-effectiveness ratio was very sensitive to a major complication such as median nerve injury. For endoscopic carpal tunnel release to be a cost-effective procedure, the incidence of median nerve injury must be one percentage point less for endoscopic carpal tunnel release than for open carpal tunnel release. Based on the data from the randomized-controlled trials, endoscopic carpal tunnel release seems to be a cost-effective procedure; however, before it can be recommended, greater emphasis must be given to the training of surgeons in this new technique, so that major complications such as median nerve injuries can be avoided. In addition, future studies must better define the actual incidence of nerve injuries for both endoscopic carpal tunnel release and open carpal tunnel release in the community setting.     

Intermediates of prothrombin activation induce intracellular calcium mobilization in rat aortic smooth muscle cells

OBJECTIVES: To determine the diagnostic utility and net cost of magnetic resonance imaging (MRI) in the management of clinically and sonographically inconclusive scrotal lesions. METHODS: A multicenter retrospective review identified 34 patients diagnosed with scrotal MRI following inconclusive clinical and ultrasound (US) evaluation. Final diagnoses were based on surgery (n = 18) or clinical and US follow-up (n = 16). Final diagnoses of 29 testicular lesions were as follows: orchitis (n = 11), infarct (n = 6), neoplasm (n = 6), rupture (n = 3), torsion (n = 2), and radiation fibrosis (n = 1). Final diagnoses of five extratesticular lesions were as follows: epididymitis (n = 2), epididymal abscess (n = 2), and neoplasm (n = 1). Management plans prior to and following MRI findings were formulated by a general urologist and a urologic oncologist. The costs of the pre-MRI and post-MRI management plans were estimated using the Medicare reimbursement schedule. RESULTS: The leading US diagnosis was correct for 10 of 34 patients (29%) and the leading MRI diagnosis was correct for 31 of 34 patients (91%). MRI improved the management plan of the general urologist and urologic oncologist in 19 patients (56%) and 17 patients (50%), respectively. MRI worsened the management plan of both clinicians in 1 patient. Management was unchanged in all other patients. The overall net cost savings were $543 to $730 per patient for the urologic oncologist and the general urologist, respectively, and $3833 per patient originally scheduled for surgery. CONCLUSIONS: Use of MRI after inconclusive clinical and US evaluation of scrotal lesions may improve management, decrease the number of surgical procedures, and result in net cost savings.     

Productivity of a breeding place of Aedes albopictus in an urban environment

BACKGROUND: Traditionally, patients presenting with uncomplicated dyspepsia have been managed using empiric antisecretory therapy, followed by endoscopy in the event of persistent symptoms or complication. Since Helicobacter pylori is now accepted as an important and potentially reversible cause of ulcer disease, it is important to reevaluate the management of dyspepsia. The goal of this study is to evaluate seven outpatient strategies for the management of dyspeptic patients using a cost-utility analysis. METHODS: The study design was that of a cost-utility analysis. The model assumes that an adult patient with signs of dyspepsia but no signs of complication presents to the outpatient office of a primary care physician. Seven strategies are modeled: empiric antisecretory therapy; empiric H pylori eradication using oral omeprazole (20 mg [corrected] twice daily), clarithromycin (500 mg twice daily), and amoxicillin (1000 mg twice daily); use of either upper endoscopy, an upper gastrointestinal barium study (an upper GI), or the serum titer for H pylori as a diagnostic test to identify patients for H pylori eradication; or use of an initial diagnostic test followed by the serum titer for H pylori. The primary outcome was the cost per quality-adjusted life year (QALY) for each strategy for a 1-year period from presentation; secondary outcomes included the probability of symptomatic ulcer recurrence, cost per ulcer cure, and mortality. RESULTS: Three strategies were similarly cost-effective: empiric H pylori eradication ($1198 per QALY), use of a serum H pylori titer as an initial diagnostic test ($1214 per QALY), and empiric antisecretory therapy ($1288 per QALY). Empiric antisecretory therapy, however, was associated with significantly more symptomatic ulcer recurrences and deaths than any other strategy. CONCLUSIONS: This cost-utility analysis suggests that two strategies are reasonable for patients presenting with dyspepsia: (1) empiric H pylori eradication and (2) use of a serum H pylori titer to identify patients who might benefit from H pylori eradication. The latter strategy may be preferable because it is less likely to lead to antibiotic resistance. Strategies utilizing an upper GI or upper endoscopy (either with or without serum H pylori titer) or empiric antisecretory therapy do not improve outcomes and are associated with greater cost, morbidity, and/or mortality.     

A phase II study of docetaxel in patients with paclitaxel-resistant metastatic breast cancer

PURPOSE: To evaluate the efficacy and safety of docetaxel in patients with paclitaxel-resistant metastatic breast cancer (MBC). PATIENTS AND METHODS: Docetaxel (100 mg/m2) was administered every 3 weeks to 46 patients registered at four centers. Patients had previously received < or = two chemotherapy regimens for MBC. All patients had progressive disease while receiving paclitaxel therapy. Treatment was repeated until there was evidence of disease progression or for a maximum of three cycles after best response. RESULTS: Objective responses were seen in eight of 44 assessable patients (18.1%; 95% confidence interval [CI], 6.7% to 29.5%). Seven patients had partial responses and one patient responded completely. Response rates were not significantly different by previously received paclitaxel dose or resistance. No responses were seen in 12 patients who had previously received paclitaxel by 24-hour infusion, but the response rate in 32 patients who had received paclitaxel by 1- to 3-hour infusion was 25%. The median response duration was 29 weeks and the median time to disease progression was 10 weeks. Median survival was 10.5 months. Clinically significant (severe) adverse events included neutropenic fever (24% of patients), asthenia (22%), infection (13%), stomatitis (9%), neurosensory changes (7%), myalgia (7%), and diarrhea (7%). CONCLUSION: Docetaxel is active in patients with paclitaxel-resistant breast cancer, particularly in those who failed to respond to brief infusions of paclitaxel. Response rates were comparable to or better than those seen with other therapies for patients with paclitaxel-resistant MBC. This confirms preclinical studies, which indicated only partial cross-resistance between paclitaxel and docetaxel.     

Chemotherapy immediately following autologous stem-cell transplantation in patients with advanced breast cancer

Most patients relapse after high-dose chemotherapy (HDCT) with autologous stem-cell transplantation (ASCT) for metastatic breast cancer. Further chemotherapy immediately after hematopoietic recovery from ASCT is not given for fear of irreversibly damaging the newly engrafted stem cells. In a pilot chemoprotection trial, autologous CD34+ cells from patients with metastatic breast cancer were exposed to a replication-incompetent retroviral vector carrying MDR-1 cDNA and then reinfused after HDCT. Immediately on recovery, patients received multiple courses of escalating dose paclitaxel. All of the 10 patients tolerated reinfusion of modified cells without any toxicity and had myeloid engraftment within 12 days (range, 11-14). The bone marrow cells of three patients contained vector MDR-1-positive cells only at the time of the first course of posttransplant paclitaxel, indicating that the MDR-1 vector-modified cells had only short-term engrafting potential. A total of 83 courses of paclitaxel were administered starting at a median of 30 (range, 21-32) days from ASCT. The median dose of paclitaxel was 225 mg/m2 and the median interval between paclitaxel cycles of therapy was 21 (range, 20-41) days. Five of the six CR patients were able to receive all of the 12 courses of paclitaxel. Three patients who had achieved less than a complete response to the HDCT (2 patients) and partial response (1 patient) were converted to complete clinical responses during the 12 cycles of paclitaxel. No delayed toxicity or bone marrow failure was noted in these patients with a median follow-up of 2 years from ASCT. This is the first study of chemotherapy immediately after transplantation with autologous CD34+ cells. These data indicate that paclitaxel can be safely administered immediately after ASCT without any delayed toxicities. Paclitaxel given immediately after ASCT can further improve the response to pretransplant chemotherapy in patients with advanced breast cancer.     

Screening for obstructive sleep apnea in patients presenting for snoring surgery

Excessive mortality is associated with obstructive sleep apnea (OSA). Therefore it is important to diagnose OSA in patients presenting for snoring surgery. A prospective study was performed to develop screening models to detect OSA compared with universal polysomnography for sensitivity and cost. Multivariate analysis of 150 consecutive patients was based on clinical data, questionnaire data, and polysomnography. Two screening models obtained 100% sensitivity and reduced the need for polysomnograms. Cost savings of screening based on clinical data was projected to be $35 to $80 per patient using reported prevalence rates of OSA among snorers. A screening model for OSA using clinical data alone is more cost-effective than one that combines these data with pulse oximetry data, but savings over universal polysomnography were modest.     

Research without billing data. Econometric estimation of patient-specific costs

OBJECTIVES: This article describes a method for computing the cost of care provided to individual patients in health care systems that do not routinely generate billing data, but gather information on patient utilization and total facility costs. METHODS: Aggregate data on cost and utilization were used to estimate how costs vary with characteristics of patients and facilities of the US Department of Veterans Affairs. A set of cost functions was estimated, taking advantage of the department-level organization of the data. Casemix measures were used to determine the costs of acute hospital and long-term care. RESULTS: Hospitalization for medical conditions cost an average of $5,642 per US Health Care Financing Administration diagnosis-related group weight; surgical hospitalizations cost $11,836. Nursing home care cost $197.33 per day, intermediate care cost $280.66 per day, psychiatric care cost $307.33 per day, and domiciliary care cost $111.84 per day. Outpatient visits cost an average of $90.36. These estimates include the cost of physician services. CONCLUSIONS: The econometric method presented here accounts for variation in resource use caused by casemix that is not reflected in length of stay and for the effects of medical education, research, facility size, and wage rates. Data on non-Veteran's Affairs hospital stays suggest that the method accounts for 40% of the variation in acute hospital care costs and is superior to cost estimates based on length of stay or diagnosis-related group weight alone.     

Cost-effectiveness of new treatments for overactive bladder: the example of tolterodine, a new muscarinic agent: a Markov model

Economic analyses of interventions for chronic diseases require evaluations over a long timeframe to illustrate the benefits and costs of treatments. Clinical trials are generally short and carried out in strictly controlled conditions. They are therefore of limited value for economic evaluation aimed at facilitating decisions about resource allocation. The objective of this study was to develop a simulation model that allows integration of data from different sources to calculate the incremental cost-effectiveness and cost-utility of new treatments for overactive bladder. The model compares tolterodine, a new treatment that aims at alleviating symptoms and improving patients' quality of life, to no treatment. Simulations for Sweden are presented as an example. The Markov model combines clinical, observational, and economic data. Markov states are defined based on severity of symptoms of overactive bladder (frequency of voids and leaks). Specific costs for drug treatment and use of sanitary protections as well as utilities are assigned for each state. The effectiveness of tolterodine is based on controlled clinical trials and open long-term extensions of these trials. Outcome is measured as quality-adjusted life years (QALYs) and as the number of months spent in a state with no or very limited symptoms. During the course of 1 year, patients treated with tolterodine spend more time in states with no or limited symptoms compared to those receiving no treatment. Tolterodine-treated patients having a better quality of life during the year. The mean utility of the treated cohort is 0.70, compared to 0.67 in the no-treatment cohort, which is equivalent to the entire cohort moving by one level to a state with less severe symptoms. Mean total costs per patient in the tolterodine arm are SEK8,595 (US $1,131; 1 US$ = 7.6 SEK) compared to SEK3,286 (US$432) in the no-treatment arm. The extra cost due to tolterodine is SEK380 (US$50) per month, which falls within the range of monthly amounts that patients were willing to pay out of pocket for a 25 or 50% improvement of their symptoms in a previous study. The cost for pads is reduced by 23%. The marginal cost per QALY gained with tolterodine is estimated at SEK213,000 (US$28,000). Based on this simulation model, it appears that treatment of overactive bladder with a well-tolerated pharmacological treatment such as tolterodine is cost-effective.