***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: This study evaluated the cost effectiveness of  bortezomib  in relapsed , refractory myeloma , relative to best supportive care ( BSC ) and thalidomide . Data were derived from the phase 2 pivotal study of bortezomib  , a Delphi panel of six myeloma thought leaders , and published literature . Objective assumptions regarding treatment choices and consequences ( response and complications ) , and actual cost data were used . Bortezomib was found to be cost effective relative to BSC and thalidomide . Sensitivity analyses demonstrated the robustness of the results . These data suggest that bortezomib provides a cost-effective treatment option and the best value ( in terms of cost/life-yr gained ) among the currently available therapeutic options for relapsed , refractory myeloma BACKGROUND In multiple myeloma , combination chemotherapy with melphalan plus prednisone is still regarded as the st and ard of care in elderly patients . We assessed whether the addition of thalidomide to this combination , or reduced-intensity stem cell transplantation , would improve survival . METHODS Between May 22 , 2000 , and Aug 8 , 2005 , 447 previously untreated patients with multiple myeloma , who were aged between 65 and 75 years , were r and omly assigned to receive either melphalan and prednisone ( MP ; n=196 ) , melphalan and prednisone plus thalidomide ( MPT ; n=125 ) , or reduced-intensity stem cell transplantation using melphalan 100 mg/m2 ( MEL100 ; n=126 ) . The primary endpoint was overall survival . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00367185 . FINDINGS After a median follow-up of 51.5 months ( IQR 34.4 - 63.2 ) , median overall survival times were 33.2 months ( 13.8 - 54.8 ) for MP , 51.6 months ( 26.6-not reached ) for MPT , and 38.3 months ( 13.0 - 61.6 ) for MEL100 . The MPT regimen was associated with a significantly better overall survival than was the MP regimen ( hazard ratio 0.59 , 95 % CI 0.46 - 0.81 , p=0.0006 ) or MEL100 regimen ( 0.69 , 0.49 - 0.96 , p=0.027 ) . No difference was seen for MEL100 versus MP ( 0.86 , 0.65 - 1.15 , p=0.32 ) . INTERPRETATION The results of our trial provide strong evidence to indicate that the use of thalidomide in combination with melphalan and prednisone should , at present , be the reference treatment for previously untreated elderly patients with multiple myeloma BACKGROUND Since 1960 , oral melphalan and prednisone ( MP ) has been regarded as the st and ard of care in elderly multiple myeloma patients . This multicentre r and omised trial compared oral MP plus thalidomide ( MPT ) with MP alone in patients aged 60 - 85 years . METHODS Patients with newly diagnosed multiple myeloma were r and omly assigned to receive oral MP for six 4-week cycles plus thalidomide ( n=129 ; 100 mg per day continuously until any sign of relapse or progressive disease ) or MP alone ( n=126 ) . Analysis was intention-to-treat . This study is registered at , number NCT00232934 . RESULTS Patients treated with thalidomide had higher response rates and longer event-free survival ( primary endpoints ) than patients who were not . Combined complete or partial response rates were 76.0 % for MPT and 47.6 % for MP alone ( absolute difference 28.3 % , 95 % CI 16.5 - 39.1 ) , and the near-complete or complete response rates were 27.9 % and 7.2 % , respectively . 2-year event-free survival rates were 54 % for MPT and 27 % for MP ( hazard ratio [ HR ] for MPT 0.51 , 95 % CI 0.35 - 0.75 , p=0.0006 ) . 3-year survival rates were 80 % for MPT and 64 % for MP ( HR for MPT 0.68 , 95 % CI 0.38 - 1.22 , p=0.19 ) . Rates of grade 3 or 4 adverse events were 48 % in MPT patients and 25 % in MP patients ( p=0.0002 ) . Introduction of enoxaparin prophylaxis reduced rate of thromboembolism from 20 % to 3 % ( p=0.005 ) . CONCLUSION Oral MPT is an effective first-line treatment for elderly patients with multiple myeloma . Anticoagulant prophylaxis reduces frequency of thrombosis . Longer follow-up is needed to assess effect on overall survival Health‐related quality of life ( HRQL ) was prospect ively measured during the phase III APEX trial of bortezomib versus dexamethasone in relapsed multiple myeloma patients .  The European Organisation for Research and Treatment of Cancer ( EORTC ) Quality of Life Question naire – Core ( QLQ‐C30 ) and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group – Neurotoxicity ( NTX ) side‐effects question naires were administered at baseline and every 6 weeks up to 42 weeks . Patients receiving bortezomib ( 1·3 mg/m2 , days 1 , 4 , 8 and 11 for eight 3‐week cycles , then days 1 , 8 , 15 and 22 for three 5‐week cycles ; n = 296 ) demonstrated significantly better mean Global Health Status over the study versus patients receiving dexamethasone ( 40 mg/d , days 1–4 , 9–12 , and 17–20 for four 5‐week cycles , then days 1–4 only for five 4‐week cycles ; n = 302 ) , plus significantly better physical health , role , cognitive , and emotional functioning scores , lower dyspnoea and sleep symptom scores , and better NTX question naire score , using multiple imputation to account for missing data . Results were similar using available‐ data analyses . Sensitivity analyses suggested that improved HRQL  with bortezomib is at least partially explained by improved survival . These results show that bortezomib was associated with significantly better multidimensional HRQL  compared with dexamethasone , consistent with the better clinical outcomes seen with bortezomib OBJECTIVES To investigate the subjective well-being of patients with newly diagnosed multiple myeloma who were treated in a t and em transplantation programme .  METHODS Fifty-one patients participated in the prospect i ve , longitudinal question naire study . The EORTC QLQ-C30 and the EuroQol-5D were administered 2 wk after completion of vincristine , adriamycin and dexamethason/vincristine , adriamycin and methyl prednison ( VAD/VAMP ) chemotherapy , both at hospital discharge after treatment with high-dose melphalan ( HDM ) and 1 month after this hospital discharge , at hospital admission , at the day of hospital discharge for peripheral stem cell transplantation ( PSCT ) and at 6 and 12 months following discharge after PSCT . RESULTS Overall , patients ' functioning improved during treatment and follow-up , with significant decreases shortly following PSCT . Shortly after HDM and PSCT , patients reported a considerable increase in levels of soreness in the mouth ( + 26/+36 points on a scale ranging form 0 to 100 ; P < 0.01 ) , change of taste ( + 23/+21 points ; P < 0.05/NS ) , nausea/vomiting ( + 26/+27 points ; P < 0.01/ < 0.05 ) , appetite loss ( + 40/+43 points ; P < 0.001 ) and diarrhoea ( + 25/+36 points ; P < 0.01 ) . However , none of these symptoms persisted during follow-up . CONCLUSION The intensive treatment programme was subjectively being well tolerated by the majority of patients . The duration of declined quality of life after administration of HDM seemed to be short . The duration of subjective recovery after PSCT remained uncertain , but in any case was present at the 6 month follow-up . Together with the rather good results in survival , the evaluation of quality of life invites further exploration of double transplantations in multiple myeloma OBJECTIVE To study the clinical course of patients with multiple myeloma ( MM ) that relapses after initial therapy . PATIENTS AND METHODS Patients with MM , seen at the Mayo Clinic in Rochester , Minn , between January 1 , 1985 , and December 31 , 1998 , were identified from a prospect ively maintained data base . Our study population consisted of 578 patients with newly diagnosed MM who were followed up and monitored throughout their clinical course at our institution . RESULTS The median age of the 578 patients with MM was 65 years ( range , 26 - 92 years ) ; 228 patients ( 39 % ) were women . The median follow-up of 71 surviving patients was 55 months ( range , 0 - 202 months ) . The overall survival ( OS ) for the 578 patients at 1 , 2 , and 5 years was 72 % , 55 % , and 22 % , respectively ; the median OS from initial therapy was 28.4 months . The median OS of 355 patients who experienced relapse after initial treatment was 17.1 months from initiation of the second therapy , and 84 % died within 5 years . The duration of response decreased consistently with each successive regimen . Patients with a high plasma cell labeling index ( > or = 1.0 % ) , low platelet count ( < 150 x 10(9)/L ) , high creatinine level ( > or = 2.0 mg/dL ) , and low albumin level ( < 3.0 g/dL ) had a poorer prognosis . CONCLUSIONS Our study revealed decreasing response duration with increasing number of salvage regimens , probably reflecting acquired drug resistance and an increasing proliferative rate of the myeloma cells . Patients who experienced relapse after initial treatment and received salvage therapy had a median survival of nearly 1.5 years . This must be remembered when making treatment decisions for these patients and must be factored in when assessing the efficacy of new therapies In a population -based study , the Nordic Myeloma Study Group found a survival advantage for high-dose melphalan with autologous blood stem-cell support compared to conventional chemotherapy in myeloma patients under 60 yr of age ( risk ratio : 1.62 ; confidence interval [ CI ] 1.22–2.15 ; p=0.001 ) . A study of health-related quality of life ( HRQoL ) was integrated in the trial , using the EORTC QLQ-C30 question naire . Of the 274 patients receiving intensive therapy 221 ( 81 % ) were compared to 113 ( 94 % ) of 120 patients receiving conventional melphalan-prednisone treatment .  Prior to treatment , there were no statistically significant differences in any HRQoL score between the two groups . One month after the start of induction chemotherapy , the patients on intensive treatment had more sleep disturbance than the control patients . At 6 mo , corresponding to a mean of 52 d after high-dose melphalan , the patients on intensive treatment had moderately lower scores for global QoL and role and social functioning and there was also a significantly higher score for appetite loss . At 12 and 24 mo , the HRQoL was similar to that of the control patients . At 36 mo , there was a trend toward less fatigue , pain , nausea , and appetite loss in the intensive-treatment group . Thus , the 18 mo of prolonged survival seem to be associated with a good health-related quality of life . Despite the moderate HRQoL reduction associated with the early intensive chemotherapy phase , this treatment modality must be regarded as an important step forward in the care of multiple myeloma A prospect i ve r and omised phase III study in patients < or = 65 years old with previously untreated multiple myeloma ( MM ) , intensive chemotherapy followed by myeloablative chemotherapy and autologous stem-cell rescue was compared with intensive chemotherapy alone . This economic evaluation was based on detailed data from patient charts and hospital information systems . In the intention-to-treat analysis , mean total treatment and follow-up costs of the myeloablative treatment arm were 81,643 euros compared to 68,802 euros for the chemotherapy arm ( P=0.09 ) . Costs per quality -adjusted life year were 51,357 euros versus 37,328 euros . In the clinical study , no significant differences were found in overall survival after a median follow-up of 33 months from r and omisation . Intensive chemotherapy is regarded as st and ard therapy for younger patients with previously untreated MM .  Cost-effectiveness of myeloma therapy after 3 years of follow up seems not to be favoured by myeloablative treatment with autologous stem-cell rescue High-dose melphalan and autologous hematopoietic stem cell transplantation ( HSCT ) is a st and ard treatment for myeloma , but very little is known about the psychosocial or quality -of-life difficulties that these patients encounter during treatment . Data regarding older 
    Output:
    
The review found that VMP and MPT can both be considered more clinical ly effective than MP for the first-line treatment of MM in people for whom high-dose therapy and SCT would not be appropriate .
CTDa was more effective than MP in terms of complete response but data on survival outcomes did not meet the inclusion criteria .
Cost-effectiveness analysis indicated that MPT has a greater probability of being cost-effective than either VMP or CTDa .
CONCLUSIONS Service provision is unlikely to change greatly .