***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: PURPOSE To investigate whether sunitinib plus docetaxel improves clinical outcomes for patients with human epidermal growth factor receptor 2 (HER2)/neu-negative advanced breast cancer ( ABC ) versus docetaxel alone . PATIENTS AND METHODS In this phase III study , patients were r and omly assigned to open-label combination therapy ( sunitinib 37.5 mg/d , days 2 to 15 every 3 weeks ; and docetaxel 75 mg/m(2 ) , day 1 every 3 weeks ) or monotherapy ( docetaxel 100 mg/m(2 ) every 3 weeks ) .  Progression-free survival ( PFS )  was the primary end point . RESULTS Two hundred ninety-six patients were r and omly assigned to combination therapy , and 297 patients were assigned to monotherapy .  Median PFS times were 8.6 and 8.3 months with combination therapy and monotherapy , respectively ( hazard ratio , 0.92 ; one-sided P = .265 ) . The objective response rate ( ORR ) was significantly higher with the combination ( 55 % ) than with monotherapy ( 42 % ; one-sided P = .001 ) . Duration of response was similar in both arms ( 7.5 months with the combination v 7.2 months with monotherapy ) . Median overall survival ( OS ) times were 24.8 and 25.5 months with combination therapy and monotherapy , respectively ( one-sided P = .904 ) . There were 107 deaths with the combination and 91 deaths with monotherapy . The frequency of common adverse events ( AEs ) was higher with the combination , as were treatment discontinuations caused by AEs . CONCLUSION The combination of sunitinib plus docetaxel improved ORR but did not prolong either PFS or OS compared with docetaxel alone when given to an unselected HER2/neu-negative cohort as first-line treatment for ABC . Sunitinib combination therapy may also have result ed in AEs that yield an unfavorable risk-benefit ratio . The sunitinib-docetaxel regimen evaluated in this study is not recommended for further use in ABC BACKGROUND In a phase III trial , 3-weekly capecitabine ( 1250 mg/m(2 ) twice daily days 1 - 14 ) plus docetaxel ( 75 mg/m(2 ) day 1 ) demonstrated significantly superior overall survival to 3-weekly docetaxel ( 100 mg/m(2 ) day 1 ) . We report a retrospective analysis of the impact of capecitabine/docetaxel dose reduction on safety and efficacy . PATIENTS AND METHODS Safety and efficacy data were analyzed retrospectively according to the actual doses of capecitabine and docetaxel administered . RESULTS More patients receiving capecitabine/docetaxel  ( 65 % ) had dose reductions for adverse events than docetaxel alone ( 35 % ) . In most patients requiring dose reduction with the combination ( 80 % ) , capecitabine and docetaxel were simultaneously reduced to 950 mg/m(2 ) and 55 mg/m(2 ) , respectively . Subsequently , there were fewer cycles ( 17 % ) with grade 3/4 adverse events than with the full doses ( 34 % ) . Time to progression and overall survival appeared to be similar in patients starting the second cycle with reduced doses of capecitabine/docetaxel and those who continued to receive full doses of capecitabine/docetaxel for at least the first four cycles . CONCLUSIONS Capecitabine/docetaxel dosing flexibility allows management of side-effects without compromising efficacy . This retrospective analysis , as well as multiple phase II studies of taxanes with reduced-dose capecitabine , shows that reducing the starting dose of capecitabine with docetaxel is a reasonable strategy for the treatment of patients with metastatic breast cancer . In addition , reducing the dose of both agents may be appropriate BACKGROUND The purpose of this study was to compare docetaxel plus epirubicin versus docetaxel plus capecitabine combinations as front-line treatment in women with advanced breast cancer ( ABC ) . PATIENTS AND METHODS Previously untreated patients with ABC were r and omly assigned to receive docetaxel 75 mg/m(2 ) plus epirubicin 75 mg/m(2 ) ( DE ) on day 1 or docetaxel 75 mg/m(2 ) on day 1 plus capecitabine 950 mg/m(2 ) orally twice daily on days 1 - 14 ( DC ) in 21-day cycles . Previous anthracycline-based (neo)-adjuvant chemotherapy was allowed if completed > 1 year before enrollment . The primary objective of the study was to compare time to disease progression ( TTP ) . RESULTS One hundred and thirty-six women were treated on each arm and median TTP was 10.6 versus 11.0 months ( P = 0.7 ) , for DE and DC , respectively . According to RECIST criteria we observed 15 ( 11 % ) versus 11 ( 8 % ) complete responses and 55 ( 40 % ) versus 61 ( 45 % ) partial responses ( P = 0.8 ) , with DE and DC , respectively . Severe toxicity included grade 3 - 4 neutropenia ( 57 % versus 46 % ; P = 0.07 ) , febrile neutropenia ( 11 % versus 8 % ; P = 0.4 ) , h and -foot syndrome ( 0 % versus 4 % ; P = 0.02 ) , grade 2 - 3 anemia ( 20 % versus 7 % ; P = 0.001 ) and asthenia ( 12 % versus 6 % ; P = 0.09 ) with DE and DC , respectively . CONCLUSIONS The DE and DC regimens have similar efficacy but different toxicity . Either regimen can be used as front-line treatment of ABC PURPOSE Dexrazoxane was found effective in reducing  doxorubicin cardiotoxicity when given at a dose ratio ( dexrazoxane : doxorubicin ) of 20:1 . Pre clinical studies indicated that dexrazoxane at a dose ratio of 10 to 15:1 also protected against epirubicin-induced cardiotoxicity . The main objective of this study was to investigate the efficacy of dexrazoxane , given at a dose ratio of 10:1 against epirubicin cardiotoxicity . PATIENTS AND METHODS One hundred sixty-two advanced breast cancer patients were r and omized to receive epirubicin-based chemotherapy with or without dexrazoxane .  Patients who had previously received adjuvant chemotherapy that contained anthracyclines were treated with cyclophosphamide 600 mg/m2 intravenously ( IV ) , epirubicin 60 mg/m2 IV , and fluorouracil 600 mg/m2 IV , on day 1 every 3 weeks . The other patients were treated with epirubicin 120 mg/m2 IV on day 1 every 3 weeks . Cardiac toxicity was defined as clinical signs of congestive heart failure , a decrease in resting left ventricular ejection fraction ( LVEF ) to < or = 45 % , or a decrease from baseline resting LVEF of > or = 20 EF units . RESULTS One hundred sixty patients were evaluated .  Cardiotoxicity was recorded in 18 of 78 patients ( 23.1 % ) in the control arm and in six of 82 ( 7.3 % ) in the dexrazoxone arm . The cumulative probability of developing cardiotoxicity was significantly lower in  dexrazoxane-treated  patients than in control patients ( P = .006 ; odds ratio , 0.29 ; 95 % confidence limit [ CL ] , 0.09 to 0.78 ) . Noncardiac toxicity , objective response , progression-free survival , and overall survival were similar in both arms . CONCLUSION Dexrazoxane given at a dexrazoxane : epirubicin dose ratio of 10:1 protects against epirubicin-induced cardiotoxicity and does not affect the clinical activity and the noncardiac toxicity of epirubicin . The clinical use of dexrazoxane should be recommended in patients whose risk of developing cardiotoxicity could hamper the eventual use and possible benefit of epirubicin Our objective was to determine whether oral etoposide and cisplatin combination ( EoP ) is superior to paclitaxel in the treatment of advanced breast cancer ( ABC ) patients pretreated with anthracyclines . From December 1997 to August 2003 , 201 patients were r and omised , 100 to EoP and 101 to paclitaxel arms . Four patients in each arm were ineligible . The doses of etoposide and cisplatin were 50 mg p.o . twice a day for 7 days and 70 mg m−2 intravenously ( i.v . ) on day 1 , respectively , and it was 175 mg m−2 on day 1 for paclitaxel . Both treatments were repeated every 3 weeks . A median of four cycles of study treatment was given in both arms . The response rate obtained in the EoP arm was significantly higher ( 36.3 vs 22.2 % ; P=0.038 ) . Median response duration was longer for the EoP arm ( 7 vs 4 months ) ( P=0.132 ) . Also , time to progression was significantly in favour of the EoP arm ( 5.5 vs 3.9 months ; P=0.003 ) . Median overall survival was again significantly longer in the EoP arm ( 14 vs 9.5 months ; P=0.039 ) . Toxicity profile of both groups was similar . Two patients in each arm were lost due to febrile neutropenia . The observed activity and acceptable toxicity of EoP endorses the employment of this combination in the treatment of ABC following anthracyclines PURPOSE An American Society of Clinical Oncology ( ASCO ) provisional clinical opinion ( PCO ) offers timely clinical direction to ASCO 's membership following publication or presentation of potentially practice -changing data from major studies . This PCO addresses the integration of palliative care services into st and ard oncology practice at the time a person is diagnosed with metastatic or advanced cancer . CLINICAL CONTEXT Palliative care is frequently misconstrued as synonymous with end-of-life care . Palliative care is focused on the relief of suffering , in all of its dimensions , throughout the course of a patient 's illness . Although the use of hospice and other palliative care services at the end of life has increased , many patients are enrolled in hospice less than 3 weeks before their death , which limits the benefit they may gain from these services . By potentially improving quality of life ( QOL ) , cost of care , and even survival in patients with metastatic cancer , palliative care has increasing relevance for the care of patients with cancer . Until recently , data from r and omized controlled trials ( RCTs ) demonstrating the benefits of palliative care in patients with metastatic cancer who are also receiving st and ard oncology care have not been available . RECENT DATA Seven published RCTs form the basis of this PCO . PROVISIONAL CLINICAL OPINION Based on strong evidence from a phase III RCT , patients with metastatic non-small-cell lung cancer should be offered concurrent palliative care and st and ard oncologic care at initial diagnosis . While a survival benefit from early involvement of palliative care has not yet been demonstrated in other oncology setting s , substantial evidence demonstrates that palliative care-when combined with st and ard cancer care or as the main focus of care-leads to better patient and caregiver outcomes . These include improvement in symptoms , QOL , and patient satisfaction , with reduced caregiver burden . Earlier involvement of palliative care also leads to more appropriate referral to and use of hospice , and reduced use of futile intensive care . While evidence clarifying optimal delivery of palliative care to improve patient outcomes is evolving , no trials to date have demonstrated harm to patients and caregivers , or excessive costs , from early involvement of palliative care . Therefore , it is the Panel 's expert consensus that combined st and ard oncology care and palliative care should be considered early in the course of illness for any patient with metastatic cancer and /or high symptom burden . Strategies to optimize concurrent palliative care and st and ard oncology care , with evaluation of its impact on important patient and caregiver outcomes ( eg , QOL , survival , health care services utilization , and costs ) and on society , should be an area of intense research . NOTE ASCO 's provisional clinical opinions ( PCOs ) reflect expert consensus based on clinical evidence and literature available at the time they are written and are intended to assist physicians in clinical decision making and identify questions and setting s for further research . Because of the rapid flow of scientific information in oncology , new evidence may have emerged since the time a PCO was su bmi tted for publication . PCOs are not continually up date d and may not reflect the most recent evidence . PCOs can not account for individual variation among patients and can not be considered inclusive of all proper methods of care or exclusive of other treatments . It is the responsibility of the treating physician or other health care provider , relying on independent experience and knowledge of the patient , to determine the best course of treatment for the patient . Accordingly , adherence to any PCO is voluntary , with the ultimate determination regarding its application to be made by the physician in light of each patient 's individual circumstances . ASCO PCOs describe the use of procedures and therapies in clinical trials and can not be assumed to apply to the use of these interventions in the context of clinical practice . ASCO assumes no responsibility for any injury or damage to persons or property arising out of 
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RECOMMENDATIONS Endocrine therapy is preferable to chemotherapy as first-line treatment for patients with estrogen receptor-positive metastatic breast cancer unless improvement is medically necessary ( eg , immediately life-threatening disease ) .
Single agent is preferable to combination chemotherapy , and longer planned duration improves outcome but must be balanced against toxicity .
Other targeted therapies have not so far been shown to enhance chemotherapy outcome in HER2-negative breast cancer