Prostate cancer (hormone refractory) - docetaxel (appraisal consultation)
NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE
Appraisal Consultation Document
Docetaxel for the treatment of hormone-refractory metastatic prostate cancer
The Department of Health and the National Assembly for Wales have asked the National Institute for Health and Clinical Excellence (NICE or the Institute) to conduct an appraisal of docetaxel for the treatment of hormone-refractory metastatic prostate cancer and provide guidance on its use to the NHS in England and Wales. The Appraisal Committee has had its first meeting to consider both the evidence submitted and the views put forward by the representatives nominated for this appraisal by professional organisations and patient/carer and service user organisations. The Committee has developed preliminary recommendations on the use of docetaxel. This document has been prepared for consultation with the formal consultees. It summarises the evidence and views that have been considered and sets out the preliminary recommendations developed by the Committee. The Institute is now inviting comments from the formal consultees in the appraisal process (the consultees for this appraisal are listed on the NICE website, www.nice.org.uk). Note that this document does not constitute the Institute's formal guidance on this technology. The recommendations made in Section 1 are preliminary and may change after consultation. The process the Institute will follow after the consultation period is summarised below. For further details, see the Guide to the Technology Appraisal Process (this document is available on the Institute's website, www.nice.org.uk).
The key dates for this appraisal are: Details of membership of the Appraisal Committee are given in Appendix A and a list of the sources of evidence used in the preparation of this document is given in Appendix B. |
Note that this document does not constitute the Institute's formal guidance on this technology. The recommendations made in Section 1 are preliminary and may change after consultation. |
| 1 | Appraisal Committee's preliminary recommendations |
| 1.1 | Docetaxel within its licensed indications is recommended as a treatment option for men with hormone-refractory metastatic prostate cancer only if their Karnofsky performance-status score (see appendix D) is 60% or more. |
| 1.2 | It is recommended that treatment with docetaxel should be stopped:
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| 1.3 | Repeat cycles of treatment with docetaxel following relapse after initial successful response are not recommended. |
| 2 | Clinical need and practice |
| 2.1 | The prostate gland is present only in men. It is located just below the bladder exit surrounding the urethra and is subdivided into three zones: central, transition and peripheral. The peripheral zone, at the back of the prostate, is the part most susceptible to prostate cancer. The extent of prostate cancer is classified into stages I-IV. At stages I and II the disease is confined to the prostate. At stage III the tumour is more locally advanced and at stage IV either it is locally advanced and invading local adjacent structures, or it has associated distant metastases. |
| 2.2 | The growth of most prostate cancers is stimulated by testosterone, and hormonal therapies that modify levels of, or responses to, testosterone are standard treatment for men with metastatic disease. Hormonal therapies are initially effective in 80% of men with metastatic prostate cancer, but after around 18 months, the disease usually becomes unresponsive to hormone treatment and will progress. |
| 2.3 | Hormone-refractory metastatic prostate cancer is defined on the basis of biochemical testing (prostate-specific antigen, PSA), findings of imaging studies, or using clinical criteria of progressive metastatic disease despite castrate serum levels of testosterone. |
| 2.4 | Data on the epidemiology of hormone-refractory metastatic prostate cancer are limited; therefore inferences must be drawn from available data for prostate cancer. In the UK, prostate cancer is the most common male cancer, excluding non-melanoma skin cancer. In 2001, there were 26,067 new cases in England and 1746 in Wales, giving age-standardised incidence rates of 89.8 and 92.6 per 100,000 men, respectively. Prostate cancer is the second most common cause of male cancer deaths, accounting for 13% of them. In 2003 there were 8582 deaths in England and 579 in Wales from prostate cancer, giving age-standardised mortality rates of 27.3 and 28.6 per 100,000 men, respectively. It has been estimated that most of the deaths are in patients with hormone-refractory metastatic prostate cancer. |
| 2.5 | Prostate cancer is associated with substantial morbidity that can have a significant impact on the patients, and on their families and carers. Prostate cancer was responsible for almost 40,000 hospital episodes in the 2003–2004 financial year, although it is unknown how many of these related to patients with hormone-refractory metastatic prostate cancer. The symptoms of hormone-refractory metastatic prostate cancer may be related to compression of the urethra, metastases to bone and other sites, and adverse effects of treatment. Urinary symptoms include difficulty starting the flow of urine, passing urine more often, and discomfort while passing urine. Over 90% of patients with late-stage prostate cancer develop metastases to bone, and this can cause debilitating and sometimes uncontrollable pain, pathological fractures and spinal cord compression. Patients may receive surgery, radiotherapy, steroids and analgesics as well as hormonal treatment and chemotherapy, and they may suffer adverse effects related to all of these. |
| 2.6 | The primary risk factor for prostate cancer is increasing age: 90% of cases are in men over 60, and 42% in men over 75. Worldwide, the highest rates are observed in African–American men, with much lower rates seen in men of Asian origin. The cause of prostate cancer is probably multi-factorial, involving environmental and genetic factors. Prostate cancer does not occur in castrated men, so testosterone is implicated. High levels of insulin-like growth factor (IGF-1), a protein involved in cell metabolism, may also be involved. About 9% of cases are thought to have a genetic component. Diets high in animal fats and dairy products appear to be associated with increased risk of prostate cancer. |
| 2.7 | The prognosis is poor for patients with hormone-refractory metastatic prostate cancer: survival is not expected to exceed between 9 and 12 months. Hormone-refractory metastatic prostate cancer cannot be cured. The aim of treatment is to improve symptoms, prolong life and slow progression of the disease. |
| 2.8 | There is no gold standard treatment for hormone-refractory metastatic prostate cancer in the UK. Clinical management is acknowledged to be multimodal rather than sequential and patients may receive a combination of palliative treatments. |
| 2.9 | Treatment options include second-line hormonal therapy, chemotherapy with or without corticosteroids, and best supportive care. The choice of therapy depends on the symptoms, the site of relapse, the performance status of the patient and the presence of other co-morbidities. Best supportive care can be provided with radiotherapy, bisphosphonates, steroids and analgesics, and is the only option for patients who are too ill to tolerate further active intervention. Tolerability of chemotherapy is of concern, particularly because most patients with prostate cancer are elderly and many have other medical problems. |
| 2.10 | Chemotherapy regimens that have been used to treat the cancer include those based on mitoxantrone, estramustine and taxanes such as docetaxel. Mitoxantrone is widely used in the UK for hormone-refractory metastatic prostate cancer patients who are fit for chemotherapy, even though it is not licensed for this indication. Several consultees have advised that a combination of mitoxantrone and prednisolone has come to be accepted as the standard care for this group of patients. |
| 2.11 | NICE's 'Guidance on cancer services: improving outcomes in urological cancers: the manual' states that chemotherapy should be considered for men with symptomatic hormone-refractory prostate cancer, trials of chemotherapy should be supported, and that palliative radiotherapy should also be available. New guidelines prepared by the British Association of Urological Surgeons propose considering the use of docetaxel for symptomatic patients who are fit for chemotherapy. |
| 3 | The technology |
| 3.1 | Docetaxel (Sanofi-Aventis) is an antineoplastic drug that belongs to a class of drugs known as taxanes. It works by disrupting the microtubular network that is essential for mitotic and interphase cellular functions, causing inhibition of cell division and cell death. |
| 3.2 | Docetaxel is licensed for use in combination with prednisone or prednisolone for the treatment of patients with hormone-refractory metastatic prostate cancer. |
| 3.3 | Docetaxel is administered as a 1-hour infusion once every 3 weeks. The recommended dose is 75 mg/m2, with daily administration of prednisone or prednisolone at a dose of 5 mg orally twice a day. |
| 3.4 | Reported adverse effects of docetaxel include hypersensitivity reactions (presenting as flushing, skin reactions, hypotension and bronchospasm), bone marrow suppression (neutropenia, thrombocytopenia, anaemia), cutaneous reactions, fluid retention, peripheral neuropathy, alopecia, cardiac disorders and tiredness. Contraindications include severe allergic reaction, low white blood cell count due to bone-marrow damage (myelosuppression), or severe liver disease. Pre-medication with a corticosteroid is usually recommended to help prevent allergic reaction. For full details of side effects and contraindications, see the Summary of Product Characteristics. |
| 3.5 | The net price is £162.75 for a 0.5 ml vial (40 mg/ml) and £534.75 for a 2 ml vial (40 mg/ml) (excluding VAT; British National Formulary, 50th edition). The cost per patient, assuming an average of seven cycles of treatment, would be approximately £8000. Costs may vary in different settings because of negotiated procurement discounts. |
| 4 | Evidence and interpretation |
| The Appraisal Committee considered evidence from a number of sources (see appendix B). | |
| 4.1 | Clinical effectiveness |
| 4.1.1 | One randomised controlled trial (RCT) that investigated docetaxel within its licensed indications was identified (TAX327). In TAX327, docetaxel plus prednisone or prednisolone was compared with mitoxantrone plus prednisone or prednisolone. |
| 4.1.2 | TAX327 was an international, multi-centre, open-label, phase III RCT. The trial enrolled 1006 men with metastatic prostate cancer with disease progression during hormonal therapy who were randomised to three chemotherapy arms, all of which received prednisone or prednisolone 5 mg orally twice daily. The chemotherapy regimens were: docetaxel at 75 mg/m2 administered every 3 weeks (335 patients); docetaxel at 30 mg/m2 administered weekly for the first 5 weeks in a 6-week cycle (334 patients); and mitoxantrone 12 mg/m2 administered every 3 weeks (337 patients). Up to 10 cycles of treatment were planned for the 3-weekly docetaxel group and the mitoxantrone group, and up to five cycles (of 6 weeks each) in the weekly docetaxel group. Patients in the docetaxel groups also received premedication with dexamethasone. |
| 4.1.3 | Patients were required to have a Karnofsky performance-status score of at least 60%, and stable levels of pain for at least 7 days before randomisation. The median length of follow-up was 20.8 months for the docetaxel 3-weekly group and 20.7 months for the other two groups. The planned treatment was delivered to 98% patients in the 3-weekly docetaxel group, 96% patients in the weekly docetaxel group and 99% in the mitoxantrone group. There was a high level of crossover between groups; 27% of patients randomised to the 3-weekly docetaxel group received mitoxantrone and 20% of patients randomised to the mitoxantrone group received docetaxel. |
| 4.1.4 | Overall survival was the primary end point for the trial and was defined as the time from the date of randomisation to the date of death from any cause or censored at the date of last contact. There was a statistically significant benefit in terms of overall survival for the 3-weekly docetaxel group compared with the mitoxantrone group, with a hazard ratio for death of 0.76 (95% confidence interval [CI], 0.62 to 0.94, p = 0.009). At the time of analysis 166/335 (50%) patients receiving 3-weekly docetaxel and 201/337 (60%) of patients receiving mitoxantrone had died. The median survival was 18.9 months (95% CI, 17.0 to 21.2) in the 3-weekly docetaxel group compared with 16.5 (95% CI, 14.4 to 18.6) months in the mitoxantrone group. |
| 4.1.5 | Quality of life response was defined as a 16-point improvement in score on the Functional Assessment of Cancer Therapy - Prostate (FACT-P) questionnaire, compared with baseline, on two measures at least 3 weeks apart. There was a statistically significant benefit in terms of quality of life response observed for the 3-weekly docetaxel group (22% [61/278] response; 95% CI, 17% to 27%) compared with the mitoxantrone group (13% [35/267] response; 95% CI, 9% to 18%), giving a relative risk of 1.67 (95% CI, 1.14 to 2.45, p = 0.009). |
| 4.1.6 | In TAX327 there was a statistically significant benefit in terms of pain response observed for the 3-weekly docetaxel group (35% [54/153] response; 95% CI, 27% to 43%) compared with the mitoxantrone group (22% [35/157] response, 95% CI, 16% to 29%), giving a relative risk of 1.58 (95% CI, 1.1 to 2.27). |
| 4.1.7 | In TAX327 a statistically significant benefit in terms of PSA response was observed for the 3-weekly docetaxel group (45% [131/291] response; 95% CI, 40% to 51%) compared with the mitoxantrone group (32% [96/300] response; 95% CI, 26% to 37%), giving a relative risk of 1.41 (95% CI, 1.14 to 1.73). |
| 4.1.8 | In TAX327 a higher proportion of grade 3 or 4 adverse events was reported in the 3-weekly docetaxel group (45.8%) than in the mitoxantrone group (34.6%). Adverse events were measured using the Common Toxicity Criteria of the US National Cancer Institute, version 2, and were reported for all 997 patients who received their planned treatment. |
| 4.1.9 | To allow for a comparison between docetaxel and relevant comparators other than mitoxantrone plus corticosteroid (for example, other chemotherapy regimens and best supportive care), the Assessment Group searched for all other treatments that were compared with mitoxantrone plus a corticosteroid, which could then be used as the common comparator. The Assessment Group performed a meta-analysis of the results from three trials comparing mitoxantrone plus a corticosteroid with corticosteroid alone. The only outcome suitable for the pooling of results was overall survival. The pooled estimate of the hazard ratio for death of mitoxantrone plus corticosteroid versus corticosteroid was 0.99 (95% CI, 0.82 to 1.20). This was then compared indirectly with that from the TAX327 study, giving an indirect hazard ratio for death of docetaxel plus prednisone or prednisolone versus corticosteroid alone of 0.752 (95% CI, 0.567 to 0.999). Results of other health outcomes were not suitable for quantitative indirect comparison, but it is notable that studies comparing mitoxantrone plus corticosteroid with corticosteroid alone resulted in improvements in various health outcomes other than mortality, and studies comparing docetaxel-based regimens with mitoxantrone plus prednisone or prednisolone also resulted in improvements in various health outcomes in addition to mortality. The Assessment Report notes that results of the adjusted indirect comparison should be interpreted with caution because the underlying trials differed in patient population and methodology. |
| 4.1.10 | Two other RCTs that investigated the effects of docetaxel in combination with estramustine in patients with hormone-refractory metastatic prostate cancer were submitted in support of the efficacy of docetaxel and included in the Assessment Report. SWOG 9916 compared docetaxel plus estramustine versus mitoxantrone plus prednisone. A statistically significant benefit, in terms of overall survival, was observed for the docetaxel plus estramustine group compared with the mitoxantrone plus prednisone group, with a hazard ratio for death of 0.80 (95%CI, 0.67 to 0.97). After a median follow-up of 32 months, 217/338 (64%) patients receiving docetaxel plus estramustine and 235/336 (70%) patients receiving mitoxantrone plus prednisone had died. There was a statistically significant difference in the proportions of reported grade 3 or 4 adverse events, which were 176/330 (53%) in patients receiving docetaxel plus estramustine, and 109/328 (33%) in patients receiving mitoxantrone plus prednisone. Oudard and coworkers investigated two different regimens of docetaxel plus prednisone plus estramustine versus mitoxantrone plus prednisone. There was a non-statistically significant reduction in the relative risk of death for patients in the docetaxel groups. The median survival was longer in the docetaxel groups than in the mitoxantrone group, but the difference was not statistically significant. |
| 4.2 | Cost effectiveness |
| 4.2.1 | The manufacturer (Sanofi-Aventis) and the Assessment Group provided estimates of cost effectiveness. Some consultees commented on economic issues. The Assessment Group developed their own economic model and critiqued the model submitted by Sanofi-Aventis. |
| Summary of evidence on cost effectiveness from the literature | |
| 4.2.2 | The Assessment Group's literature search did not yield any suitable cost-effectiveness studies of docetaxel-based treatment regimens. One study was found that compared mitoxantrone and prednisone with prednisone alone and was based on the CCI-NOV-22 RCT. That study was used to inform the follow-up costs of the Assessment Group's economic model. |
| 4.2.3 | The Assessment Group undertook a systematic review of literature on measurement of the utility associated with the health-related quality of life of patients with hormone-refractory metastatic prostate cancer, and used the results of that review to inform inputs of its economic model. |
| Summary of evidence of cost-effectiveness from the manufacturer | |
| 4.2.4 | The Sanofi-Aventis model estimates the incremental cost per life-year gained from docetaxel plus prednisone or prednisolone compared with mitoxantrone plus prednisone or prednisolone. No adjustment is made for quality of life. The evaluation was based on an analysis of patient-level data derived from prospective collection of resource use and patient outcome data from the TAX327 trial. Only the 3-weekly regimen of docetaxel was considered in the analysis, in keeping with the licensed recommended dose. Two analyses are presented: the preliminary analysis uses the difference in median survival within the TAX327 trial as the measure of clinical benefit, and the base case uses an estimate of the mean difference in survival extrapolated beyond the trial period; data extrapolation is used to characterise the survival of patients beyond the period of follow-up in the trial. The sponsor submission states that in economic valuation, mean survival times are preferred to medians to provide the best estimate of relative cost effectiveness between two competing interventions. Uncertainty is considered by way of two different one-way sensitivity analyses, one related to the estimate of survival, and the other to that of costs per patient. |
| 4.2.5 | The base case result of the Sanofi-Aventis model was £19,483 as the incremental cost per life year gained from docetaxel plus prednisone or prednisolone over mitoxantrone plus prednisone or prednisolone. In the preliminary analysis, the incremental cost per life year gained was £30,280. |
| Summary of economic evaluation undertaken by the Assessment Group | |
| 4.2.6 | The Assessment Group model estimates the incremental cost per quality-adjusted life year (QALY) gained by using docetaxel plus prednisone or prednisolone compared with the least expensive strategy, not excluded by dominance or extended dominance, of a number of treatment comparators. Two analyses were reported. Analysis 1 compares docetaxel 3-weekly plus prednisone or prednisolone, mitoxantrone plus prednisone or prednisolone, and best supportive care in the form of prednisone or prednisolone alone. Analysis 2 extends this comparison to include the full range of potential comparators identified in the clinical effectiveness review. In both base cases, and all reported sensitivity analyses, the relevant resulting incremental cost-effectiveness ratio (ICER) is that of docetaxel 3-weekly plus prednisone or prednisolone (as the licensed regimen) compared with mitoxantrone plus prednisone or prednisolone (as the cheapest non-dominated strategy). Uncertainty is characterised by way of probabilistic sensitivity analysis, as well as three different one-way sensitivity analyses. |
| 4.2.7 | The main results of the Assessment Group model indicate that docetaxel plus prednisone or prednisolone appears cost-effective compared with other chemotherapy and non-chemotherapy regimens, as long as the NHS is willing to pay at least £32,706 per QALY. The use of prednisone or prednisolone alone appears to be dominated by (that is, it is less effective and more costly than) mitoxantrone plus prednisone or prednisolone. Therefore, the cost-effectiveness of docetaxel plus prednisone or prednisolone is most appropriately informed by a comparison against mitoxantrone plus prednisone or prednisolone. Three one-way sensitivity analyses were undertaken to test the robustness of the model to alternative assumptions about discount rates, quality of life estimates and the impact of side effects. The ICER associated with docetaxel (3-weekly) plus prednisone or prednisolone remained fairly robust to these variations, with estimates ranging from £28,019 to £33,298 per QALY. |
| 4.3 | Consideration of the evidence |
| 4.3.1 | The Committee reviewed the data available on the clinical and cost effectiveness of docetaxel for hormone-refractory metastatic prostate cancer, having considered evidence on the nature of the condition and the value placed on the benefits of docetaxel by people with hormone-refractory metastatic prostate cancer, those who represent them, and clinical experts. It was also mindful of the need to take account of the effective use of NHS resources. |
| 4.3.2 | The Committee noted that prednisone was used as an alternative to prednisolone in the RCTs. It was aware that prednisone is a pro-drug of prednisolone, and that in the UK prednisolone has historically been preferred to prednisone on the grounds that it does not require conversion to the active substance. The Committee concluded that in practice the difference between prednisone and prednisolone was not clinically significant and therefore accepted the relevance of the results of international studies to the appraisal. |
| 4.3.3 | The Committee understood from the testimony of the clinical experts that docetaxel is the first treatment to show survival benefit in this group of patients. The Committee was persuaded, from the review of the evidence for the effectiveness of docetaxel in improving the survival of patients with hormone-refractory metastatic prostate cancer that there was a significant survival advantage for the docetaxel 3-weekly regimen over treatment with mitoxantrone, as opposed to the weekly regimen, for which there was no statistically significant difference. It also considered that this differential effect between the two docetaxel regimens was consistent with its mode of action. The Committee considered evidence from the SWOG 9916 trial and noted that its results added weight to the evidence of the effect on overall survival of a 3-weekly regimen of docetaxel compared with treatment with mitoxantrone. |
| 4.3.4 | The Committee discussed the evidence for the effects of docetaxel on quality of life and palliation of disease. It concluded that, whereas the survival advantage of the docetaxel 3-weekly regimen had been demonstrated, there was insufficient evidence to support the assertion that docetaxel provides benefits in quality of life and palliation over and above those associated with the use of mitoxantrone. |
| 4.3.5 | The Committee carefully considered the adverse events related to docetaxel and the differential adverse events associated with a 3-weekly docetaxel regimen as opposed to a weekly regimen were discussed. The clinical experts indicated that patients receiving weekly docetaxel are more likely to experience painful and debilitating nail dystrophia whereas this is less common in those receiving the drug 3-weekly. However the 3-weekly regimen was associated with a higher incidence of neutropenia. Additionally the Committee heard from both the clinical experts and the patient representatives that many patients feel that the benefits of treatment with docetaxel outweigh the side effects. The Committee concluded that the adverse events related to docetaxel, when weighed against the potential for beneficial effects, should not preclude recommendation of the use of docetaxel in patients with hormone-refractory metastatic prostate cancer. |
| 4.3.6 | The Committee considered the assumptions and sensitivity analyses of the economic models put forward by the manufacturer and the Assessment Group. The utility value used to quality-adjust life years in the Assessment Group model was discussed and the Committee noted that the base case input was derived from a study in a large sample using appropriate methodology. The potential for additional quality of life benefits conferred by docetaxel compared with mitoxantrone was discussed. The Committee discussed at length the estimation of patients' mean survival, and the number of chemotherapy cycles received per patient. It noted that although both had been obtained through extrapolation beyond the duration of clinical trials, the estimates were similar in the manufacturer's model and the Assessment Group model. It was concluded that the estimates were reasonable given the available evidence. |
| 4.3.7 | The Committee discussed the uncertainty surrounding the generalisability of the evidence from the RCT to everyday clinical practice. It was aware that the patients enrolled into the pivotal trial (TAX327) generally were younger and had a higher performance status than those who typically present for treatment in the UK. The Committee heard from the clinical experts that performance status, as defined by the Karnofsky score, was an important predictor of the likelihood of benefit from treatment for individual patients, irrespective of age. The Committee therefore decided that the recommendation on the use of docetaxel for patients with hormone-refractory metastatic prostate cancer should be limited to patients who have a Karnofsky score of 60% or more, an entry requirement of the TAX327 RCT. The experts agreed that such an approach would be appropriate. |
| 4.3.8 | The Committee also discussed the lack of evidence and the uncertainty surrounding the generalisability of the results of the TAX327 RCT with regard to duration of treatment. The Committee heard testimony from the experts that in clinical practice the duration of treatment is determined by the balance of clinical benefit against the occurrence of adverse events and in practice it is rare for patients to receive more than six cycles of 3-weekly docetaxel therapy. The Committee therefore concluded, in agreement with the experts and in accordance with the stopping rules of the TAX327 RCT, that treatment should be stopped either in the presence of progression of disease as evidenced by clinical, radiological or laboratory criteria or the presence of severe adverse events, and that patients should not receive more than a maximum of 10 cycles of treatment. |
| 4.3.9 | The Committee heard testimony from clinical experts that the interpretation of the definition of hormone-refractory metastatic prostate cancer in section 2.3 may vary in clinical practice in terms of the number and type of hormonal treatments the patient has had. The Committee was therefore satisfied that it was not appropriate to limit the recommendation to patients who had received a particular number of hormonal manipulations. |
| 4.3.10 | The Committee considered that the use of docetaxel in hormone-refractory metastatic prostate cancer was both clinically and cost effective on the basis of the above considerations and where the treatment protocol was that which was shown to be clinically effective in the pivotal RCT (TAX327) namely the 3-weekly docetaxel regimen administered for a maximum of 10 cycles only. In addition the Committee considered that there was no evidence to support a recommendation for further cycles of docetaxel therapy, if disease relapse occurred following successful initial response to this treatment protocol. |
| 5 | Proposed recommendations for further research |
| 5.1 | The Committee noted that there are ongoing trials, which include the MRC STAMPEDE study, and trials in which docetaxel plus prednisone or prednisolone is the standard treatment arm and is used in combination with other therapies such as zoledronic acid, strontium-89 and bevacizumab, in the experimental treatment arm. |
| 5.2 | The Committee identified a need for research assessing the quality of life associated with different treatments for hormone-refractory metastatic prostate cancer including adverse events of treatment, using generic quality of life instruments that are suitable for the purposes of cost-effectiveness analyses. The Committee also identified a need for research that would yield data regarding the effects of docetaxel over a longer follow-up period, and in a patient group that is more representative of the wider patient population in terms of age, performance status and co-morbidity, than the RCTs considered in this appraisal. |
| 6 | Preliminary views on the resource impact for the NHS |
This section outlines the Appraisal Committee's preliminary assessment concerning the likely impact on NHS resources if the recommendations in section 1 were to be implemented. When guidance is issued, this section is intended to assist NHS planners and managers in its implementation. Therefore the Institute particularly welcomes comments and information from those who would be involved in the implementation of the guidance so that this section can be made as helpful and robust as possible. The NICE Costing Unit is currently developing this section. A costing template and report will be available at the time of publication of the final guidance. |
| 7 | Proposals for implementation and audit |
| This section presents proposals for implementation and audit based on the preliminary recommendations for guidance in section 1. | |
| 7.1 | NHS organisations and clinicians who care for men with prostate cancer should review their current practice and policies to take account of the guidance set out in section 1. |
| 7.2 | Local guidelines, protocols or care pathways that refer to the care of men with prostate cancer should incorporate the guidance. |
| 7.3 To measure compliance locally with the guidance, the following criteria could be used. Further details on suggestions for audit are presented in appendix C. | |
| 7.3.1 | A man with hormone-refractory metastatic prostate cancer is offered docetaxel within its licensed indications as a treatment option only if his Karnofsky performance-status score is 60% or more. |
| 7.3.2 | For a man with hormone-refractory metastatic prostate cancer who is treated with docetaxel, treatment with docetaxel is stopped when any of the following circumstances occur: ? planned treatment up to 10 cycles is completed, or ? the man experiences a severe adverse event, or ? there is evidence of progression of disease. |
| 7.3.3 | Repeat cycles of treatment with docetaxel following relapse after initial successful response are not provided. |
| 8 | Related guidance |
| 8.1 | NICE has commissioned the National Collaborating Centre for Cancer to develop a guideline on the diagnosis and treatment of prostate cancer for use in the NHS in England and Wales. |
| 8.2 | The following technology has been referred to NICE for appraisal: The use of atrasentan for hormone-refractory prostate cancer. |
| 8.3 | NICE has issued the the following related cancer service guidance: ? Improving outcomes in urological cancers: the manual. NICE cancer service guidance (2002). Available from www.nice.org.uk/csguc |
| 9 | Proposed date for review of guidance |
| 9.1 | The review date for a technology appraisal refers to the month and year in which the Guidance Executive will consider whether the technology should be reviewed. This decision will be taken in the light of information gathered by the Institute, and in consultation with consultees and commentators. |
| 9.2 | It is proposed that the guidance on this technology is considered for review after 3 years. The Institute would particularly welcome comment on this proposed date. |
David Barnett |
Chair, Appraisal Committee |
December 2005 |
| Appendix A. Appraisal Committee members |
| The Appraisal Committee is a standing advisory committee of the Institute. Its members are appointed for a 3-year term. A list of the Committee members who took part in the discussions for this appraisal appears below. The Appraisal Committee meets twice a month except in December, when there are no meetings. The Committee membership is split into two branches, with the chair, vice chair and a number of other members attending meetings of both branches. Each branch considers its own list of technologies and ongoing topics are not moved between the branches. |
| Committee members are asked to declare any interests in the technology to be appraised. If it is considered there is a conflict of interest, the member is excluded from participating further in that appraisal. |
| The minutes of each Appraisal Committee meeting, which include the names of the members who attended and their declarations of interests, are posted on the NICE website. |
| Dr Jane Adam
Radiologist, St George's Hospital, London |
| Professor A E Ades MRC Senior Scientist, MRC Health Services Research Collaboration, Department of Social Medicine, University of Bristol |
| Dr Tom Aslan General Practitioner, Stockwell, London |
| Professor David Barnett (Chair) Professor of Clinical Pharmacology, University of Leicester |
| Mrs Elizabeth Brain Independent Patient Advocate |
| Dr Karl Claxton Health Economist, University of York |
| Dr Richard Cookson Senior Lecturer in Health Economics, School of Medicine Health Policy and Practice, University of East Anglia |
| Mrs Fiona Duncan Clinical Nurse Specialist, Anaesthetic Department, Blackpool Victoria Hospital, Blackpool |
| Professor Christopher Eccleston Director Pain Management Unit, University of Bath |
| Dr Paul Ewings Statistician, Taunton and Somerset NHS Trust, Taunton |
| Professor Terry Feest Professor of Clinical Nephrology, Southmead Hospital, Bristol |
| Ms Alison Forbes Lay Representative, Health Consultant Associate, Eden Insight |
| Professor John Geddes Professor of Epidemiological Psychiatry, University of Oxford |
| Mr John Goulston Director of Finance, Barts and the London NHS Trust |
| Mr Adrian Griffin Health Outcomes Manager, Johnson & Johnson Medical |
| Ms Linda Hands Consultant Surgeon, John Radcliffe Hospital |
| Dr Elizabeth Haxby Lead Clinician in Clinical Risk Management, Royal Brompton Hospital |
| Dr Rowan Hillson Consultant Physician, Diabeticare, The Hillingdon Hospital |
| Dr Catherine Jackson Clinical Lecturer in Primary Care Medicine, Alyth Health Centre, Angus, Scotland |
| Professor Richard Lilford Professor of Clinical Epidemiology, Department of Public Health and Epidemiology, University of Birmingham |
| Dr Simon Mitchell Consultant Neonatal Paediatrician, St Mary's Hospital, Manchester |
| Ms Judith Paget Chief Executive, Caerphilly Local Health Board, Wales |
| Dr Katherine Payne Health Economist, The North West Genetics Knowledge Park, The University of Manchester |
| Dr Ann Richardson Independent Patient Advocate |
| Mrs Kathryn Roberts Nurse Practitioner, Hattersley Group Practice, Cheshire |
| Professor Philip Routledge Professor of Clinical Pharmacology, College of Medicine, University of Wales, Cardiff |
| Dr Stephen Saltissi Consultant Cardiologist, Royal Liverpool University Hospital |
| Mr Mike Spencer General Manager, Clinical Support Services, Cardiff and Vale NHS Trust |
| Dr Debbie Stephenson Head of HTA Strategy, Eli Lilly and Company |
| Professor Andrew Stevens (Vice Chair) Professor of Public Health, University of Birmingham |
| Dr Cathryn Thomas General Practitioner, and Associate Professor, Department of Primary Care and General Practice, University of Birmingham |
| Dr Norman Vetter Reader, Department of Epidemiology, Statistics and Public Health, College of Medicine, University of Wales, Cardiff |
| Professor Mary Watkins Professor of Nursing, University of Plymouth |
| Dr Paul Watson Medical Director, Essex Strategic Health Authority |
| Dr David Winfield Consultant Haematologist, Royal Hallamshire Hospital, Sheffield |
| NICE Project Team |
| Each appraisal of a technology is assigned to a Health Technology Analyst and a Technology Appraisal Project Manager within the Institute. |
| Helen Chung Technical Lead |
| Sarah Garner Technical Advisor |
| Alana Miller Project Manager |
| Appendix B. Sources of evidence considered by the Committee | |
| A | The assessment report for this appraisal was prepared by Systematic Reviews Centre for Reviews and Dissemination,
This page was last updated: 30 March 2010 |