Sunitinib, sorafenib, temsirolimus or bevacizumab in the treatment of metastatic renal cell carcinoma: a review of health economic evaluations.

Renal cell carcinoma (RCC) is the most prevalent kidney cancer and the 5-year overall survival figure in metastatic disease (mRCC) is about 10%. New targeted drugs (sunitinib, sorafenib, bevacizumab, temsirolimus) have shown activity in the treatment of mRCC, but they are all associated with a significant burden of cost. To support decision makers in their allocation of resources, costeffectiveness models are constructed to compare the costs and outcomes of anticancer therapy. This survey focuses on studies since 2003 exploring health economics in the treatment of metastatic and/or advanced RCC employing these new drugs. This paper summarizes the results, focuses on the level of evidence of these studies, compares the calculated cost-effectiveness ratios and makes suggestions for future studies. This review reveals costs per life years gained (LYG) or quality-adjusted life years (QALY) in the range of euro 22,648 to euro203,692, depending on whether the setting is first-line or second-line and drug used. When compared to the other agents, sunitinib has the best cost-effectiveness figure. Second-line therapy does not offer valid incremental cost-effectiveness ratios.

Economic evaluation of chemoprevention of breast cancer with tamoxifen and raloxifene among high-risk women in Japan.

Raloxifene was approved for chemoprevention against breast cancer among high-risk women in addition to tamoxifen by the US Food and Drug Administration. This study aims to evaluate cost-effectiveness of these agents under Japan's health system. A cost-effectiveness analysis with Markov model consisting of eight health states such as healthy, invasive breast cancer, and endometrial cancer is carried out. The model incorporated the findings of National Surgical Adjuvant Breast and Bowel Project P-1 and P-2 trial, and key costs obtained from health insurance claim reviews. Favourable results, that is cost saving or cost-effective, are found by both tamoxifen and raloxifene for the introduction of chemoprevention among extremely high-risk women such as having a history of atypical hyperplasia, a history of lobular carcinoma in situ or a 5-year predicted breast cancer risk of > or =5.01% starting at younger age, whereas unfavourable results, that is 'cost more and gain less' or cost-ineffective, are found for women with a 5-year predicted breast cancer risk of < or =5.00%. Therapeutic policy switch from tamoxifen to raloxifene among postmenopausal women are implied cost-effective. Findings suggest that introduction of chemoprevention targeting extremely high-risk women in Japan can be justifiable as an efficient use of finite health-care resources, possibly contributing to cost containment.

The Kadota Fund International Forum 2004--clinical group consensus.

The results from experimental studies indicate that hyperthermia is both an effective complementary treatment to, and a strong sensitiser of, radiotherapy and many cytotoxic drugs. Since the first international hyperthermia conference in 1975, Washington DC, techniques to increase tumour temperature have been developed and tested clinically. Hyperthermia can be applied by several methods: local hyperthermia by external or internal energy sources, perfusion hyperthermia of organs, limbs, or body cavities, and whole body hyperthermia. The clinical value of hyperthermia in combination with other treatment modalities has been shown by randomised trials. Significant improvement in clinical outcome has been demonstrated for tumours of the head and neck, breast, brain, bladder, cervix, rectum, lung, oesophagus, for melanoma and sarcoma. The addition of hyperthermia resulted in remarkably higher (complete) response rates, accompanied by improved local tumour control rates, better palliative effects, and/or better overall survival rates. Toxicity from hyperthermia cannot always be avoided, but is usually of limited clinical relevance. In spite of these good clinical results, hyperthermia has received little attention. Problems with acceptance concern the limited availability of equipment, the lack of awareness concerning clinical results, and the lack of financial resources. In this paper the most relevant literature describing the clinical effects of hyperthermia is reviewed and discussed, and means to overcome the lack of awareness and use of this modality is described.

Assessment of local cone on- and off-pathway function using multifocal ERG technique.

There is evidence that recording the photopic ON- and OFF-responses with long-duration stimuli is useful for determining the contribution of the cone ON- and OFF-pathways to the primate photopic electroretinogram (ERG). In this study, the optimal conditions for recording multifocal ON-OFF responses are described, and the technique is applied to normal subjects and two patients with unusual retinal diseases. The results from the normal subjects demonstrated that there were topographical variations of the photopic ERG waveform: when responses were normalized to the ON-response (b-wave) amplitude, the OFF-response (d-wave) amplitude increased with increasing eccentricity. The changes in the waveform in two patients suggested relatively greater defects of the hyperpolarizing or depolarizing bipolar cells. We conclude that the multifocal ERG technique with long-duration stimuli can be a useful tool to assess the function of local cone ON- and OFF-pathways in normal and diseased retinas.

Assessment of "microvascular no-reflow phenomenon" using technetium-99m macroaggregated albumin scintigraphy in patients with acute myocardial infarction.

OBJECTIVES: The aim of this study was the scintigraphic evaluation of clinical no-reflow phenomenon. BACKGROUND: In patients with acute myocardial infarction, the relationship of the severity of reduction of microvascular reflow to the ischemia time or to the secondary extension of myocardial necrosis is poorly understood, and we accordingly conducted a scintigraphic evaluation of clinical no-reflow phenomenon. METHODS: The group studied consisted of 25 consecutive patients with their first acute myocardial infarction. After recanalization, each patient received intracoronary injections of technetium-99m macroaggregated albumin (MAA). RESULTS: Eight patients (32%) had absent tracer uptake (scintigraphic no-reflow phenomenon). Fourteen patients showed absent or moderately reduced MAA uptake (group 1) and 11 showed slightly reduced or normal uptake (group 2). The time to recanalization was significantly longer in group 1 than in group 2 (290.4+/-130.6 min vs. 1773+/-93.5 min; p=0.0238). In chronic phase, the thallium-201 (TI-201) defect score index was significantly larger (p < 0.01) and regional ejection fraction was significantly lower (p < 0.01) in group 1 compared with corresponding values in group 2. No significant deterioration from acute phase to chronic phase in either TI-201 defect score index or regional ejection fraction was found in either group (two-way repeated measures analysis of variance). CONCLUSIONS: These findings suggest that scintigraphic noreflow phenomenon occurs in a subgroup of patients without angiographic no-reflow phenomenon, that the myocardial damage depends on the severity of microvascular damage and that prolonged ischemia time may increase the likelihood of "microvascular no-reflow phenomenon."

Assessment of left ventricular myocardial perfusion and diastolic function during acetylcholine-induced diffuse coronary vasoconstriction by Doppler echocardiography and thallium-201 scintigraphy.

BACKGROUND: We investigated whether diffuse coronary vasoconstriction induced by acetylcholine caused myocardial ischemia. METHODS: We studied 30 patients (40 coronary arteries) with spontaneous chest pain or equivocal studies on treadmill exercise testing and no significant coronary stenosis or previous myocardial infarction. During the acetylcholine provocation test, Doppler echocardiography was performed, and thallium-201 was injected intravenously for scintigraphy. We used Doppler echocardiography to measure the ratio of early-to-late peak mitral flow (E:A ratio). RESULTS: When acetylcholine was injected, the coronary arteries showed three different responses. Diffuse coronary vasoconstriction without chest pain or ischemic changes on the ECG was induced in 18 (45%) arteries and the E:A ratio decreased from 0.83 +/- 0.13 to 0.77 +/- 0.13 (P = 0.031). In 17 vessels (control arteries), the E:A ratio did not change significantly (from 0.88 +/- 0.15 to 0.88 +/- 0.18; P = 0.95). In five arteries, focal spasm was induced and the E:A ratio decreased from 0.83 +/- 0.18 to 0.66 +/- 0.13 (P = 0.043). Transient defects on thallium-201 scintigraphy were observed in the territory of eight (80%) arteries with diffuse vasoconstriction and in one (20%) control artery (P = 0.047). CONCLUSIONS: Diffuse coronary vasoconstriction induced by intracoronary acetylcholine can decrease the regional myocardial blood flow (as shown by thallium-201 scintigraphy) and can cause global left ventricular diastolic dysfunction (as shown by the results of Doppler echocardiography).

[Apparent depth by the stereograms without binocular retinal disparity: is Lau effect artifact?].

We examined the idea that, when the Zöllner figure in one eye and the principal lines in the figure in the other eye were presented, the perceived depth is due to "phenomenal" disparity. The phenomenal disparity is defined as apparent displacement between two illusory "oblique" principal lines in one eye and two "parallel" principal lines in the other. Observes were asked whether depth was seen or not at upper or lower part of the two perceived lines and, if seen, which line was closer. Seventeen observers showed that only 9% of their responses was consistent with the idea, although they reported depths for disparity stimuli. This suggests that the dichoptic presentation of such figures should not be considered as that requires the processing of binocular disparity.

[A simplified method for the assessment of C1 esterase inhibitor function].

From the result that the activated form of C1-s(C1-s) prolonged the kinetics of hemolysis via complement, this assay was applied to assess C1 esterase inhibitor (C1INH) function. In the kinetic assay, the complement hemolytic activity was evaluated by the time which required to cause 50% reduction of the initial turbidity of sensitized sheep erythrocytes, and was expressed as T1/2. (1) T1/2 of pooled normal human sera (p-NHS) showed dose-dependent prolongation by the addition of various amounts of C1-s. (2) Preincubation of various amounts of functionally pure C1INH with the constant amounts of C1-s inhibited dose-dependently the prolongation of T1/2 by C1-s. (3) The C1INH activity of NHS was 840 +/- 80 units/ml (n = 6) and that of the C1INH deficient serum was 80 units/ml, which were calculated from the standard curve established by the addition of various amounts of purified C1INH. This test requiring only C1-s and sensitized sheep erythrocytes is simple technically and high in sensitivity, and seems to be useful for the routine assay for C1INH function of human sera.

Assessment of viable myocardium within infarct zone by exercise thallium-201 scintigraphy.

The viability of the myocardial regions corresponding to pathologic Q waves was evaluated. Thirty-four patients with prior myocardial infarction underwent serial thallium-201 scintigraphy during treadmill exercise testing. On the delayed images, 8 of the initial 85 segmental defects (8 patients, 9%) showed total redistribution (RD) and 11 (6 patients, 13%) showed partial RD. In contrast, 66 segments showed persistent defect. The segments with total RD were more likely to be associated with normal or hypokinetic wall motion than the segments with persistent defect (p less than 0.05). Six of the 38 segments (13%) with collateral vessels showed total RD and 10 (21%) showed partial RD. However, 35 of 38 segments (92%) without collateral vessels showed persistent defect. There was a significant difference (p = 0.02) in myocardial thallium uptake patterns when the segments with and without collateral vessels were compared. It is concluded that (1) exercise-induced thallium RD may occur in patients with prior myocardial infarction, and myocardial infarct regions with total RD are highly associated with good contractility; these suggest the presence of viable but jeopardized myocardium within the infarct zone, and (2) collateral vessels may play a role in limiting infarct size.