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

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30 Results TABLE 11 Grade 3 or 4 adverse events for mitoxantrone plus prednisone versus prednisone Adverse event Mitoxantrone group Prednisone group (n = 81) (n = 80) (%) (prior to crossover) (%) Leucopenia 15 0 Neutropenia 54 1 Thrombocytopenia 1 0 Anaemia 1 – TABLE 12 Summary results table for mitoxantrone plus prednisone versus prednisone of last follow-up. At the time of analysis, there had been 58 deaths out of 119 patients in the mitoxantrone group and 68 deaths out of 123 patients in the hydrocortisone group. There was no statistically significant benefit in terms of overall survival observed for the mitoxantrone group compared with the hydrocortisone group; unadjusted HR for death (calculated from numbers of events and p-value presented in the trial publication) = 1.05 (95% CI: 0.74 to 1.49, p = 0.77). When adjusting for baseline PSA, haemoglobin, lactate dehydrogenase and alkaline phosphatase levels, there was still no statistically significant difference in overall survival between groups; HR for death = 1.0 (95% CI: 0.8 to 1.3, p = 0.976). The median overall survival was 12.3 months in the mitoxantrone group and 12.6 months for the hydrocortisone group. Progression-free survival Time to disease progression was defined as the time from randomisation to a worsening of performance status by at least one point, the appearance of two or more new lesions on bone scan or an increase of at least 100% in serum PSA level from baseline. At the time of analysis, 56 patients in the Mitoxantrone group Prednisone group Comparison Mortality HR = 0.91 (95% CI: 0.69 to 1.19) Failure/time to progression 43/77 (56%) 60/70 (86%) HR = 2.15 (95% CI: 1.46 to 3.17) Response rate 23/80 (29%) 10/81 (12%) RR = 2.33 (95% CI: 1.19 to 4.57) QoL response Variety of measures Pain response See response rate PSA decline 19/57 (33%) 12/54 (22%) RR = 1.5 (95% CI: 0.81 to 2.79) Adverse events: Discontinued 11 1 Grade 3/4 22 15 Died Not reported Not reported mitoxantrone group and 71 patients in the hydrocortisone group had progressed. There was a statistically significant benefit in terms of time to disease progression for the mitoxantrone group compared with the hydrocortisone group; HR for time to progression (calculated from number of events and p-value presented in the trial publication) = 1.50 (95% CI: 1.06 to 2.13, p = 0.0218). The median time to disease progression was 3.7 months for the mitoxantrone group compared with 2.3 months for the hydrocortisone group. Response rate A complete response was defined as the disappearance of all disease by scans, and normalisation of PSA levels, sustained for at least 28 days. For those with measurable tumours, partial response was defined as a 50% or more reduction in bi-dimensional measurements for at least 4 weeks or an 80% or more reduction of serum PSA level from baseline sustained for at least 6 weeks. For patients with assessable and bone-only disease, the latter criteria only defined a partial response. The analysis of response rates was based only on the 234 participants receiving study treatment; of
these, 69 patients had measurable tumours. No complete responses were observed in either group. Partial responses were observed in eight (7%) patients in the mitoxantrone group and five (4%) patients in the hydrocortisone group. There was no statistically significant difference in terms of response rate between groups; RR for response = 1.65 (95% CI: 0.56 to 4.91, p = 0.375). Health-related quality of life HRQoL was assessed using five instruments. The Functional Living Index – Cancer (FLIC) with scores ranging from 0 to 7 was used to provide a global assessment of QoL. Four other HRQoL instruments were used to provide in-depth evaluations of cancer-related symptoms, sexual and urological issues, problems with everyday activities and the impact of pain on activities such as sleep and normal work. A total of 155 (66%) patients were assessed at baseline and at least one follow-up. The estimated treatment effects showed that there was no statistically significant benefit for the mitoxantrone group compared with the hydrocortisone group in terms of global QoL as assessed by the FLIC questionnaire (p = 0.12). Some of the items of the questionnaires did show statistically significant benefits for the mitoxantrone group compared with the hydrocortisone group in relation to emotional state and family disruption (p = 0.04 and 0.02, respectively, as assessed by FLIC) and severity of pain (p = 0.03 as assessed by the symptom distress scale). Pain Data on pain were measured and reported with the HRQoL assessments. Specific items assessed by the QoL instruments and reported were the total impact of pain, frequency of pain, severity of pain and pain from cancer; only the last item showed a tendency for those in the hydrocortisone group to have a better QoL than those in the mitoxantrone group. PSA decline PSA decline was defined as at least a 50% reduction and at least an 80% reduction in serum PSA from baseline at a follow-up examination between 4 and 8 weeks. A post hoc Health Technology Assessment 2007; Vol. 11: No. 2 TABLE 13 Grade 3 or 4 haematopoietic adverse events for mitoxantrone plus hydrocortisone versus hydrocortisone Adverse event Mitoxantrone group (%) Hydrocortisone group (%) White blood count 59 1 Platelets 6 0 Granulocytes/bands 63 1 Lymphocytes 70 15 © Queen’s Printer and Controller of HMSO 2007. All rights reserved. analysis was also performed to determine the maximum PSA decrease over the duration of the whole trial. The original analysis of PSA decline included 187 patients for whom PSA measurements were available and the post hoc analysis included 228 participants. Between 4 and 8 weeks, 18 (18.7%) patients in the mitoxantrone group had achieved a PSA decline of at least 50% and, of these, four (4.2%) achieved a PSA decline of 80% or more. During the same time interval, 13 (14.3%) patients in the hydrocortisone group achieved a PSA decline of at least 50% and, of these, four (4.3%) achieved a PSA decline of 80% or more. These differences were not statistically significant (p = 0.412). The post hoc analysis of PSA decline over the duration of the whole trial showed that 42 (37.5%) patients in the mitoxantrone group achieved a 50% or greater decline in PSA and, of these, 22 (19.6%) experienced a decline of 80% or more. In the hydrocortisone group, 25 (21.5%) patients had PSA decreases of 50% or more and of these, 11 (9.5%) had declines of 80% or more. There was a statistically significant benefit for the mitoxantrone group compared with the hydrocortisone group with respect to PSA decline throughout the trial, both for declines of at least 50% (p = 0.008) and declines of at least 80% (p = 0.029). Adverse effects of treatment Grade 3 and 4 specific toxicities were reported for 206 (86%) patients. There were no observed treatment-related deaths in either group. The most common treatmentrelated adverse event reported for the mitoxantrone group was haematopoietic toxicity, occurring in approximately 70% of patients. There were statistically significant differences between the two treatment groups in terms of the haematopoietic toxicities reported (p < 0.01). Table 13 shows the proportion of patients experiencing grade 3 or 4 haematopoietic toxicities. Summary Summary results are given in Table 14. 31
Page 1 and 2: A systematic review and economic mo
Page 3 and 4: A systematic review and economic mo
Page 5 and 6: Objectives: A systematic review was
Page 7 and 8: Glossary and list of abbreviations
Page 9 and 10: Glossary Absolute risk reduction Th
Page 11 and 12: Glossary continued Expected value o
Page 13 and 14: Glossary continued Progression-free
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
Page 29 and 30: consensus and, if necessary, a thir
Page 31 and 32: Quantity of research available A to
Page 33 and 34: TABLE 1 Summary of included RCTs St
Page 35 and 36: TABLE 2 Treatment comparisons relat
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Page 39 and 40: TABLE 4 Summary results table for d
Page 41 and 42: decrease in PSA level (51 and 39% c
Page 43 and 44: Survival (%) 100 80 60 40 20 0 0 co
Page 45 and 46: TABLE 8 Summary results table for d
Page 47 and 48: TABLE 9 Grade 3 or 4 adverse events
Page 49: Also used was the core questionnair
Page 53 and 54: Effectiveness of mitoxantrone plus
Page 55 and 56: over to receive additional mitoxant
Page 57 and 58: Progression-free survival It is not
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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
Page 75 and 76: TABLE 28 Regression coefficients fr
Page 77 and 78: cancer QoL estimation. Studies whic
Page 79 and 80: Localised Metastatic mHRPC Bennet (
Page 81 and 82: TABLE 34 Unit costs of drugs from t
Page 83 and 84: were assigned to the total follow-u
Page 85 and 86: Probability cost-effective given da
Page 87 and 88: Probability cost-effective given da
Page 89 and 90: TABLE 43 Utility values including/e
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Page 93: Population value of implementation/
Page 96 and 97: 76 Discussion (CCI-NOV22) and least
Page 98 and 99: 78 Discussion subsequent chemothera
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Rodolphe Perard received funding fr
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84 References Compendium; 2004. URL
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86 References (D) in patients (pts)
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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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