***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: BACKGROUND We have previously demonstrated that vincristine , liposomal doxorubicin and dexamethasone ( VAD-doxil ) is equally effective with VAD-bolus yielding objective response rates of 61 % as first-line treatment in multiple myeloma ( MM ) . In a phase II study , the addition of thalidomide to VAD-doxil ( TVAD-doxil ) proved feasible and increased response rate to 74 % . The aim of the present multicenter prospect i ve r and omized clinical trial was to compare the efficacy and toxicity of VAD-doxil and TVAD-doxil in previously untreated MM patients . PATIENTS AND METHODS We enrolled 232 newly diagnosed MM patients aged < 75 years , 115 r and omized to VAD-doxil ( arm A ) and 117 to TVAD-doxil ( arm B ) . Patients in arm A received vincristine 2 mg i.v . and liposomal doxorubicin 40 mg/m(2 ) i.v . , on day 1 and dexamethasone 40 mg p.o . daily on days 1 - 4 , 9 - 12 and 17 - 20 for the first cycle and on days 1 - 4 for the next three cycles . Patients in arm B received additionally thalidomide 200 mg p.o . daily , at bedtime . Treatment was administered every 28 days . RESULTS On an intention-to-treat basis , at least partial response was observed , in 62.6 % and in 81.2 % of patients r and omized to arms A and B , respectively ( P = 0.003 ) . Progression-free survival ( PFS ) at 2 years was 44.8 % in arm A and 58.9 % in arm B ( P = 0.013 ) . Overall survival ( OS ) at 2 years was 64.6 % and 77 % , in arms A and B , respectively ( P = 0.037 ) . Considering overall toxicity , constipation , peripheral neuropathy , dizziness/somnolence , skin rash and edema were significantly higher in arm B compared with arm A ( P < 0.01 ) , but grade 3 - 4 toxicities were low and similar in both arms . CONCLUSIONS The addition of thalidomide to VAD-doxil increases response and PFS rates and probably OS in previously untreated myeloma patients . The superiority of efficacy counterbalances the higher overall toxicity of TVAD-doxil Newer chemotherapeutic protocol s as well as high-dose chemotherapy have increased the response rate in myeloma . However , these treatments are not curative . Effective maintenance strategies are now required to prolong the duration of response . We conducted a r and omized trial of maintenance treatment with thalidomide and pamidronate . Two months after high-dose therapy , 597 patients younger than age 65 years were r and omly assigned to receive no maintenance ( arm A ) , pamidronate ( arm B ) , or pamidronate plus thalidomide ( arm C ) . A complete or very good partial response was achieved by 55 % of patients in arm A , 57 % in arm B , and 67 % in arm C ( P = .03 ) . The 3-year postr and omization probability of event-free survival was 36 % in arm A , 37 % in arm B , and 52 % in arm C ( P < .009 ) . The 4-year postdiagnosis probability of survival was 77 % in arm A , 74 % in arm B , and 87 % in arm C ( P < .04 ) . The proportion of patients who had skeletal events was 24 % in arm A , 21 % in arm B , and 18 % in arm C ( P = .4 ) . Thalidomide is an effective maintenance therapy in patients with multiple myeloma . Maintenance treatment with pamidronate does not decrease the incidence of bone events 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 PURPOSE To determine if thalidomide plus dexamethasone yields superior response rates compared with dexamethasone alone as induction therapy for newly diagnosed multiple myeloma . PATIENTS AND METHODS Patients were r and omly assigned to receive thalidomide plus dexamethasone or dexamethasone alone . Patients in arm A received thalidomide 200 mg orally for 4 weeks ; dexamethasone was administered at a dose of 40 mg orally on days 1 to 4 , 9 to 12 , and 17 to 20 . Cycles were repeated every 4 weeks . Patients in arm B received dexamethasone alone at the same schedule as in arm A. RESULTS Two hundred seven patients were enrolled : 103 were r and omly assigned to thalidomide plus dexamethasone and 104 were r and omly assigned to dexamethasone alone ; eight patients were ineligible . The response rate with thalidomide plus dexamethasone was significantly higher than with dexamethasone alone ( 63 % v 41 % , respectively ; P = .0017 ) . The response rate allowing for use of serum monoclonal protein levels when a measurable urine monoclonal protein was unavailable at follow-up was 72 % v 50 % , respectively . The incidence rates of grade 3 or higher deep vein thrombosis ( DVT ) , rash , bradycardia , neuropathy , and any grade 4 to 5 toxicity in the first 4 months were significantly higher with thalidomide plus dexamethasone compared with dexamethasone alone ( 45 % v 21 % , respectively ; P < .001 ) . DVT was more frequent in arm A than in arm B ( 17 % v 3 % ) ; grade 3 or higher peripheral neuropathy was also more frequent ( 7 % v 4 % , respectively ) . CONCLUSION Thalidomide plus dexamethasone demonstrates significantly superior response rates in newly diagnosed myeloma compared with dexamethasone alone . However , this must be balanced against the greater toxicity seen with the combination PURPOSE To determine whether interferon maintenance therapy improves overall survival and response duration in patients with multiple myeloma who have responded to induction therapy with melphalan and prednisone .  PATIENTS AND METHODS In a multicenter trial , patients with symptomatic clinical stage I and stage II and III multiple myeloma were registered at diagnosis and those who responded to melphalan-prednisone ( MP ) were r and omized either to receive interferon ( 2 mU/m2 ) subcutaneously three times per week or no maintenance . MP was discontinued in both groups once a stable response plateau of the monoclonal protein was reached . Interferon was continued until relapse , and then was restarted on subsequent response to MP . Interferon toxicity was recorded using a self-report diary . Survival and response duration were calculated using life-table methods , and were adjusted in the analysis for imbalances in baseline prognostic factors . RESULTS Four hundred two patients were registered and 176 responders were r and omized ( 85 to interferon and 91 to control ) . At a median follow-up time of 43 months , the median survival duration was 43 months for interferon and 35 months for control ( P = .16 ) , but when adjusted for chance imbalances in baseline prognostic factors ( mainly performance status ) , the median survival duration was 44 months and 33 months for interferon and control , respectively ( P = .049 ) . Progression-free survival from r and omization to first relapse also favored interferon ( unadjusted P < .002 ; adjusted P < .003 ) .  Interferon toxicity caused 58 % of patients to reduce their dose , of which 84 % were able to return to the initial dose ; 14 % had to discontinue interferon treatment . CONCLUSION Interferon maintenance therapy improves progression-free and overall survival of patients with multiple myeloma who respond to melphalan and prednisone .  Toxicity is substantial and must be weighed by patients against the potential benefits in response duration and survival BACKGROUND High-dose therapy with supporting autologous stem-cell transplantation remains a controversial treatment for cancer . In multiple myeloma , first-line regimens incorporating high-dose therapy yield higher remission rates than do conventional-dose treatments , but evidence that this translates into improved survival is limited . METHODS In this multicenter study , the Medical Research Council Myeloma VII Trial , we r and omly assigned 407 patients with previously untreated multiple myeloma who were younger than 65 years of age to receive either st and ard conventional-dose combination chemotherapy or high-dose therapy and an autologous stem-cell transplant . RESULTS Among the 401 patients who could be evaluated , the rates of complete response were higher in the intensive-therapy group than in the st and ard-therapy group ( 44 percent vs. 8 percent , P<0.001 ) . The rates of partial response were similar ( 42 percent and 40 percent , respectively ; P=0.72 ) , and the rates of minimal response were lower in the intensive-therapy group than in the st and ard-therapy group ( 3 percent vs. 18 percent , P<0.00 
    Output:
    
In summary , thalidomide appears to improve the overall survival of patients with newly diagnosed myeloma both when it is added to st and ard , non-transplantation therapy , and when it is given as maintenance therapy following ASCT .
However , thalidomide is associated with toxicity , particularly a significantly increased risk of VTE