***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: INTRODUCTION With the widespread use of sequential anthracycline/taxane-based chemotherapy for early-stage breast cancer , clinicians are becoming rapidly aware of toxicities associated with those regimens . Despite the low incidence reported in the literature of significant arthralgia and myalgia with those regimens , it is clinical ly evident that a substantial proportion of patients develop such toxicities . We performed a pilot study to investigate the extent of this problem . PATIENTS AND METHODS Patients who had received prior adjuvant or neoadjuvant chemotherapy [ doxorubicin-cyclophosphamide followed by paclitaxel ( AC-T ) , doxorubicin-cyclophosphamide followed by docetaxel ( AC-D ) , or 5-fluourouracil-epirubicin-cyclophosphamide followed by docetaxel ( FEC-D ) ]  completed a retrospective outcomes -based survey . The survey utilized the Functional Assessment of Cancer Therapy-Taxane Scale , the Memorial Symptom Assessment Scale , and a modified Brief Pain Inventory . RESULTS Interviews were conducted with 82 patients . Interviewees had received AC-T ( 43 % ) , FEC-D ( 43 % ) , and AC-D ( 14 % ) . Pain as a side effect of either the anthracycline or the taxane chemotherapy was reported by 87 % of patients . Most of the patients ( 79 % ) indicated that their worst pain occurred during the taxane component of treatment . Compared with paclitaxel , docetaxel was reported to cause more pain . Narcotics for pain management were required by 35 of 82 patients ( 43 % ) . CONCLUSIONS A significant number of patients receiving sequential  anthracycline/taxane-based chemotherapy for early-stage breast cancer experience pain , particularly during the taxane component . Prospect i ve patient-reported outcome assessment s are needed to help individualize treatment interventions and to improve symptom management in this population The Memorial Symptom Assessment Scale ( MSAS ) is a new patient-rated instrument that was developed to provide multidimensional information about a diverse group of common symptoms . This study evaluated the reliability and validity of the MSAS in the cancer population . R and omly selected in patients and out patients ( n = 246 ) with prostate , colon , breast or ovarian cancer were assessed using the MSAS and a battery of measures that independently evaluate phenomena related to quality of life . Symptom prevalence in the 218 evaluable patients ranged from 73.9 % for lack of energy to 10.6 % for difficulty swallowing . Based on a content analysis , three symptoms were deleted and two were added ; the revised scale evaluates 32 physical and psychological symptoms . A factor analysis of variance yielded two factors that distinguished three major symptom groups and several subgroups . The major groups comprised psychological symptoms ( PSYCH ) , high prevalence physical symptoms ( PHYS H ) , and low prevalence physical symptoms ( PHYS L ) . Internal consistency was high in the PHYS H and PSYCH groups ( Cronback alpha coefficients of 0.88 and 0.83 , respectively ) , and moderate in the PHYS L group ( alpha = 0.58 ) . Although the severity , frequency and distress dimensions were highly intercorrelated , canonical correlations and other analyses demonstrated that multidimensional assessment ( frequency and distress ) augments information about the impact of symptoms . High correlations with clinical status and quality of life measures support the validity of the MSAS and indicate the utility of several subscale scores , including PSYCH , PHYS , and a brief Global Distress Index . The MSAS is a reliable and valid instrument for the assessment of symptom prevalence , characteristics and distress . It provides a method for comprehensive symptom assessment that may be useful when information about symptoms is desirable , such as clinical trials that incorporate quality of life measures or studies of symptom epidemiology Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more BACKGROUND Mitoxantrone plus prednisone reduces pain and improves the quality of life in men with advanced , hormone-refractory prostate cancer , but it does not improve survival . We compared such treatment with docetaxel plus prednisone in men with this disease . METHODS From March 2000 through June 2002 , 1006 men with metastatic hormone-refractory prostate cancer received 5 mg of prednisone twice daily  and were r and omly assigned to receive 12 mg of mitoxantrone per square meter of body-surface area every three weeks , 75 mg of docetaxel per square meter every three weeks , or 30 mg of docetaxel per square meter weekly for five of every six weeks . The primary end point was overall survival . Secondary end points were pain , prostate-specific antigen ( PSA ) levels , and the quality of life . All statistical comparisons were against mitoxantrone . RESULTS As compared with the men in the mitoxantrone group , men in the group given docetaxel every three weeks had a hazard ratio for death of 0.76 ( 95 percent confidence interval , 0.62 to 0.94 ; P=0.009 by the stratified log-rank test ) and those given weekly docetaxel had a hazard ratio for death of 0.91 ( 95 percent confidence interval , 0.75 to 1.11 ; P=0.36 ) . The median survival was 16.5 months in the mitoxantrone group , 18.9 months in the group given docetaxel every 3 weeks , and 17.4 months in the group given weekly docetaxel . Among these three groups , 32 percent , 45 percent , and 48 percent of men , respectively , had at least a 50 percent decrease in the serum PSA level ( P<0.001 for both comparisons with mitoxantrone ) ; 22 percent , 35 percent ( P=0.01 ) , and 31 percent ( P=0.08 ) had predefined reductions in pain ; and 13 percent , 22 percent ( P=0.009 ) , and 23 percent ( P=0.005 ) had improvements in the quality of life . Adverse events were also more common in the groups that received docetaxel . CONCLUSIONS When given with prednisone , treatment with docetaxel every three weeks led to superior survival and improved rates of response in terms of pain , serum PSA level , and quality of life , as compared with mitoxantrone plus prednisone BACKGROUND Docetaxel administered every 3 weeks is a st and ard treatment for castration-resistant advanced prostate cancer . We hypothesised that 2-weekly administration of docetaxel would be better tolerated than 3-weekly docetaxel in patients with castration-resistant advanced prostate cancer , and did a prospect i ve , multicentre , r and omised , phase 3 study to compare efficacy and safety . METHODS Eligible patients had advanced prostate cancer ( metastasis , a prostate-specific-antigen test result of more than 10·0 ng/mL , and WHO performance status score of 0 - 2 ) , had received no chemotherapy ( except with estramustine ) , had undergone surgical or chemical castration , and had been referred to a treatment centre in Finl and , Irel and , or Sweden . Enrolment and treatment were done between March 1 , 2004 , and May 31 , 2009 . R and omisation was done central ly and stratified by centre and WHO performance status score of 0 - 1 vs 2 . Patients were assigned 75 mg/m(2 ) docetaxel intravenously on day 1 of a 3-week cycle , or 50 mg/m(2 ) docetaxel intravenously on days 1 and 15 of a 4-week cycle . 10 mg oral prednisolone was administered daily to all patients . The primary endpoint was time to treatment failure ( TTTF ) . We assessed data in the per- protocol population . This study is registered with Clinical Trials.gov , number NCT00255606 . FINDINGS 177 patients were r and omly assigned to the 2-weekly docetaxel  group and 184 to the 3-weekly group . 170 patients in the 2-weekly group and 176 in the 3-weekly group were included in the analysis . The 2-weekly administration was associated with significantly longer TTTF than was 3-weekly administration ( 5·6 months , 95 % CI 5·0 - 6·2 vs 4·9 months , 4·5 - 5·4 ; hazard ratio 1·3 , 95 % CI 1·1 - 1·6 , p=0·014 ) . Grade 3 - 4 adverse events occurred more frequently in the 3-weekly than in the 2-weekly administration group , including neutropenia ( 93 [ 53 % ] vs 61 [ 36 % ] ) , leucopenia ( 51 [ 29 % ] vs 22 [ 13 % ] ) , and febrile neutropenia ( 25 [ 14 % ] vs six [ 4 % ] ) . Neutropenic infections were reported more frequently in patients who received docetaxel every 3 weeks ( 43 [ 24 % ] vs 11 [ 6 % ] , p=0·002 ) . INTERPRETATION Administration of docetaxel every 2 weeks seems to be well tolerated in patients with castration-resistant advanced prostate cancer and could be a useful option when 3-weekly single-dose administration is unlikely to be tolerated . FUNDING Sanofi BACKGROUND The endothelin pathway has a role in bone metastases , which are characteristic of advanced prostate cancer . Atrasentan , an endothelin receptor antagonist , has shown activity in prostate cancer . We therefore assessed its effect on survival in patients with castration-resistant prostate cancer with bone metastases . METHODS In a double-blind phase 3 trial , men with metastatic castration-resistant prostate cancer , stratified for progression type ( prostate-specific antigen or radiological ) , baseline pain , extraskeletal metastases , and bisphosphonate use , were r and omly assigned in a 1:1 ratio to docetaxel ( 75 mg/m(2 ) every 21 days , intravenously ) with atrasentan ( 10 mg/day , orally ) or placebo for up to 12 cycles and treated until disease progression or unacceptable toxicity . Patients who did not progress on treatment were permitted to continue atrasentan or placebo for up to 52 weeks . Co primary endpoints were progression-free survival ( PFS ) and overall survival . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00134056 . FINDINGS 498 patients were r and omly assigned to the atrasentan group and 496 to the placebo group . The trial was halted early for futility in April , 2011 , after a planned interim analysis . Median PFS was 9·2 months ( 95 % CI 8·5 - 9·9 ) in the atrasentan group and 9·1 months ( 8·4 - 10·2 ) in the placebo group ( hazard ratio 1·02 , 0·89 - 1·16 ; p=0·81 ) . Median overall survival was 17·8 months ( 16·4 - 19·8 ) in the atrasentan group versus 17·6 months ( 16·4 - 20·1 ) in the placebo group ( 1·04 , 0·90 - 1·19 ; p=0·64 ) . 278 ( 57 % ) of 492 patients in the atrasentan group had grade 3 and greater toxicity compared with 294 ( 60 % ) of 486 in the placebo group ( p=0·22 ) . Three deaths in the atrasentan group and seven in the placebo group were judged to be possibly or probably due to protocol treatment . INTERPRETATION Atrasentan , when added to docetaxel , does not improve overall survival or PFS in men with castration-resistant prostate cancer and bone metastases ; therefore , single-agent docetaxel should remain as one of the st and ard treatments . FUNDED National Cancer Institute , Sanofi-Aventis , and Abbott Laboratories Myalgias and arthralgias are prominent toxicities associated with paclitaxel . Pursuant to pilot information suggesting that glutamine could markedly alleviate this toxicity , we developed a placebo-controlled , double-blind , r and omized crossover trial to test this hypothesis . This trial studied 36 patients who had experienced myalgias/arthralgias related to a prior paclitaxel-containing regimen and who were then r and omized to receive oral glutamine ( 10 grams three times a day , starting on the day of chemotherapy ) x 5 days or an identical-appearing placebo . For the subsequent cycle of chemotherapy , patients were crossed over , again in a double-blind manner , to receive the alternative treatment . Patients recorded daily myalgia/arthralgia scores on numerical scales . Physicians recorded patient-reported myalgias/arthralgias using National Cancer Institute common toxicity criteria at baseline and after each course of therapy . The results of this study revealed that glutamine had no effect on the development or severity of paclitaxel-induced myalgias/arthralgias , as recorded either by the patients ' daily logs or by physician-reported information . Glutamine 
    Output:
    
Clinical risk factors were identified in 4 studies , suggesting that TAPS was numerically more common in the castrate‐resistant setting and when concurrent medications ( eg , corticosteroids ) were not used .
Although the TAPS incidence has been poorly reported in clinical practice , the results of the present study suggest that arthralgia and myalgia are a common toxicity in patients with prostate cancer .