Docetaxel with prednisone or prednisolone for the treatment of ...

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40 Results mitoxantrone plus a corticosteroid versus a corticosteroid’ (p. 34). Therefore, patients in all of the trials are receiving the ‘common comparator’ similarly. However, it still must be assumed that prednisone is equivalent to hydrocortisone in these circumstances. Differences in populations The trials used to obtain a pooled estimate in the section ‘Pooled estimate of effectiveness of mitoxantrone plus a corticosteroid versus a corticosteroid’ (p. 34) had varying inclusion criteria and therefore included patient populations with varying degrees of disease severity, from asymptomatic patients to patients experiencing pain with analgesic requirements. The inclusion criteria for TAX 327 restricted eligibility to those with progressive mHRPC. This means that this trial was conducted with a varied patient population which included both asymptomatic and symptomatic patients. However, all patients included in the indirect comparison had to have progressive mHRPC to be eligible for inclusion. Hence the patient populations between trials can be regarded as a relatively homogeneous subset of patients healthy enough to receive chemotherapy. Also, the adjusted indirect comparisons approach aims to obtain an unbiased estimate of treatment effect even if there are different prognostic characteristics between study participants in the trials included in the comparison. 62 Results of the indirect comparison Using the method proposed by Bucher and colleagues 63 and considering carefully the various restrictions and assumptions for performing adjusted indirect comparisons, an indirect comparison was undertaken for overall survival only for the comparison of docetaxel plus prednisone versus corticosteroids. Using the random effects pooled estimate for mitoxantrone plus corticosteroids versus corticosteroids derived in the section ‘Pooled estimate of effectiveness of mitoxantrone plus a corticosteroid versus a corticosteroid’ (p. 34), the estimated HR for death is 0.75 (95% CI: 0.57 to 0.99). Full details of the calculations are presented in Appendix 8. The results of this adjusted indirect comparison suggest that docetaxel plus prednisone is superior to corticosteroids alone in improving overall survival. However, as the upper 95% CI is very close to unity, this finding is of borderline statistical significance. As detailed in the previous section, CCI-NOV22 is perhaps the trial most comparable to TAX 327 in terms of treatment and the fact that crossovers were allowed in both, although the baseline prognostic factors of the patients in CCI-NOV22 were generally worse than those in TAX 327. However, one of the aims of using an adjusted indirect comparison approach is to reduce the possibility of bias introduced by any differences in prognostic characteristics between the populations included in the comparison. 62 This means that it is possible that the CCI-NOV22 is the most relevant and comparable trial within this adjusted indirect comparison. Performing the indirect comparison again, using only the result from CCI-NOV22, we obtain an estimated HR for death of 0.69 (95% CI: 0.49 to 0.97). This clearly shows that the initial estimated HR using the pooled treatment effect is more conservative. For the adjusted indirect comparison to give an accurate estimate of the difference in treatment effect between competing interventions, a number of assumptions have to be made, especially with regard to the similarities of the trials involved in the indirect comparisons and in particular the patients included in the trials and the doses and schedules of interventions used. Because of these assumptions, the findings of the adjusted indirect comparisons should be interpreted with due caution. Indirect comparisons that do not include a comparison with docetaxel plus prednisone should not be undertaken, because the search strategy did not include searches for all available evidence that could inform such comparisons. Trials assessing the efficacy of other chemotherapies or docetaxel in combination with any other treatment were not searched for, so there may be trials that could provide additional information if any further indirect comparisons were made. For the indirect comparison of docetaxel plus prednisone versus corticosteroids, all available evidence that could inform the comparison has been included. Summary of clinical effectiveness One trial was found that assessed the intervention under consideration: docetaxel plus prednisone; this was in comparison with mitoxantrone plus prednisone (TAX 327). No other trials were found that assessed the clinical effectiveness of docetaxel plus prednisone. The results of this trial showed
statistically significant improvements with 3-weekly docetaxel plus prednisone compared with mitoxantrone plus prednisone, in terms of overall survival, QoL, pain response and PSA decline. The response rate was higher for the 3-weekly docetaxel plus prednisone group than the mitoxantrone plus prednisone group, but this difference was not statistically significant. The improved outcomes for docetaxel plus prednisone were associated with more grade 3–4 adverse events; however, this had no detrimental effect on QoL, which was significantly improved in the 3weekly docetaxel group. Progression-free survival was not assessed in this trial. Since docetaxel plus prednisone is only compared with mitoxantrone plus prednisone, it was considered important to consider other evidence which would inform a comparison against other potentially relevant comparators (e.g. other chemotherapy-based treatments and best supportive care). Therefore, we searched for all other treatments that were compared with mitoxantrone plus a corticosteroid. Three trials were found comparing mitoxantrone plus prednisone with another chemotherapy regimen: one trial that compared mitoxantrone plus prednisone with docetaxel plus prednisone plus estramustine, one trial that compared mitoxantrone plus prednisone with docetaxel plus estramustine, and one trial that compared mitoxantrone plus prednisone with mitoxantrone plus prednisone plus clodronate. Both treatments that included docetaxel were superior to mitoxantrone plus prednisone in terms of overall survival (although the difference was not statistically significant for docetaxel plus prednisone plus estramustine), response rate (although the difference was not statistically significant for docetaxel plus estramustine) and progression-free survival (although this was only assessed for docetaxel plus estramustine in comparison with mitoxantrone plus prednisone). Docetaxel plus estramustine was associated with more adverse events compared with mitoxantrone plus prednisone. No significant differences were found between mitoxantrone plus prednisone plus clodronate and mitoxantrone plus prednisone without clodronate. In addition, three trials were found that compared mitoxantrone plus a corticosteroid with best supportive care, that is, corticosteroids. Two of these used prednisone (5 mg twice daily) as the comparator and one compared mitoxantrone plus hydrocortisone with hydrocortisone (40 mg given © Queen’s Printer and Controller of HMSO 2007. All rights reserved. Health Technology Assessment 2007; Vol. 11: No. 2 in two divided doses daily). One of the trials included men with asymptomatic mHRPC, another included men with symptomatic mHRPC, with symptoms including pain and disease progression, and the third included all men with progressive mHRPC. One trial allowed patients to cross over during the trial, which resulted in 50 out of 81 patients randomised to prednisone to receive additional mitoxantrone; the other two trials did not allow crossovers. The combined result of these three trials showed very little difference between mitoxantrone plus corticosteroids compared with corticosteroids alone in terms of overall survival [HR = 0.99 (95% CI: 0.82 to 1.20)]. Other outcomes could not be pooled because they were measured differently in the three trials. However, in the two studies that measured HRQoL and pain responses, the mitoxantrone groups had statistically significant improvements compared with the corticosteroid groups. An adjusted indirect comparison was performed to estimate the relative efficacy of docetaxel plus prednisone versus corticosteroids. The results of the indirect comparison showed that docetaxel plus prednisone seems to be superior to prednisone alone in terms of overall survival. However, this is based on an indirect comparison using one good-quality trial comparing docetaxel plus prednisone with mitoxantrone plus prednisone (TAX 327) and three trials comparing mitoxantrone plus corticosteroids with corticosteroids, that differed in terms of patient population and methodology. Therefore, the results of this indirect comparison need to be interpreted with caution. In summary, a direct comparison of docetaxel plus prednisone versus mitoxantrone plus prednisone in an open-label, randomised trial showed statistically significant higher overall survival for docetaxel plus prednisone. Other outcomes, such as response rate, QoL, pain response and PSA decline, were also in favour of docetaxel plus prednisone. These improved outcomes were associated with more grade 3–4 adverse events; however, this had no detrimental effect on QoL, which was significantly improved in the docetaxel plus prednisone group. Two other chemotherapy regimens were found that included docetaxel: docetaxel plus estramustine and docetaxel plus prednisone plus estramustine; both were superior to mitoxantrone plus prednisone in terms of overall survival, response rate and progression-free survival. Three trials that compared mitoxantrone plus a corticosteroid with a corticosteroid alone 41
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A systematic review and economic mo
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A systematic review and economic mo
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Objectives: A systematic review was
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Glossary and list of abbreviations
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Page 15: List of abbreviations ASCO American
Page 18 and 19: xvi Executive summary of study desi
Page 20 and 21: xviii Executive summary prednisone/
Page 23 and 24: Description of underlying health pr
Page 25 and 26: ● Patients with severe fluid rete
Page 27 and 28: Search strategy As stated in Chapte
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Page 63 and 64: Summary of studies included in the
Page 65 and 66: TABLE 19 Percentage of costs by res
Page 67 and 68: TABLE 21 Summary of submission by S
Page 69 and 70: TABLE 24 Other in-trial costs a bod
Page 71 and 72: TABLE 27 Cost-effectiveness results
Page 73 and 74: Introduction The review of cost-eff
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Page 98 and 99: 78 Discussion subsequent chemothera
Page 101: Rodolphe Perard received funding fr
Page 104 and 105: 84 References Compendium; 2004. URL
Page 106 and 107: 86 References (D) in patients (pts)
Page 108 and 109: 88 References 100. Aventis Pharma.
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90 References low-dose prednisone i
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92 References 180. Kozloff M, Robin
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94 References locally advanced pros
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96 References 251. Scholz MC, Guess
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Clinical effectiveness Searching fo
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1. Prostatic Intraepithelial Neopla
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19. donataxel 20. doxetal 21. doxmi
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6. Mitozantrone.ti,ab. 7. Mitoxantr
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Texot or Trazoteva or Trixotene or
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1. (docetaxel OR asodecel OR doxeta
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10. (index of wellbeing or quality
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Appendix 2 Excluded studies Study d
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Study details Reason for exclusion
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Meeting: 2004 ASCO Annual Meeting C
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Studies of clinical effectiveness w
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Using the method outlined by Parmar
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Appendix 6 Data extraction tables
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Study details and Participant detai
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158 Appendix 7 Ernst et al. 33 Qual
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Appendix 9 © Queen’s Printer and
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Sanofi-Aventis 61 Bloomfield et al.
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Sanofi-Aventis 61 Bloomfield et al.
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168 Appendix 10 TABLE 51 Mean (SD)
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170 Appendix 10 TABLE 54 Distributi
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172 Appendix 10 TABLE 57 Mean stand
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174 Appendix 11 TABLE 63 Drug and a
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176 Appendix 12 Scenario: moderate
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178 Appendix 13 ● You occasionall
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Members Chair, Professor Tom Walley
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Members Chair, Professor Bruce Camp
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Feedback The HTA Programme and the
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