human
***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: Platinum/taxane combinations are widely used in patients with carcinoma of unknown primary ( CUP ) , yielding response rates of 30 % and median overall survival of 9–11 months in selected patients . Yet these combinations have not been subject to a r and omised trial to overcome selection bias , a major problem in CUP . We r and omised 92 patients to either paclitaxel/carboplatin ( arm A ) or the non-platinum non-taxane regimen gemcitabine/vinorelbine ( arm B ) . The primary endpoint was rate of practicability as defined : application of ⩾2 cycles of therapy ( 1 ) with a maximal delay of 1 week ( 2 ) and survival of ⩾8 months ( 3 ) . Practicability was shown in 52.4 % ( 95 % CI 36–68 % ) in arm A and in 42.2 % ( 95 % CI 28–58 % ) in arm B , respectively . The median overall survival , 1-year survival -rate and response rate of patients treated in arm A was 11.0 months , 38 , and 23.8 % , arm B 7.0 months , 29 , and 20 % . In conclusion , the paclitaxel/carboplatin regimen showed clinical ly meaningful activity in this r and omised trial ( Clinical trial registration number 219 , ‘ Deutsches KrebsStudienRegister ’ , German Cancer Society . INTRODUCTION This phase II trial evaluated the efficacy and toxicity of the combination of paclitaxel , carboplatin , bevacizumab , and erlotinib in the first-line treatment of patients with carcinoma of unknown primary site ( CUP ) . METHODS Patients with previously untreated CUP ( adenocarcinoma , poorly differentiated carcinoma , poorly differentiated squamous carcinoma ) without clinical or pathologic characteristics of a well-defined treatable subset were eligible . All patients received paclitaxel , carboplatin , bevacizumab , and erlotinib . Treatment cycles were repeated at 21-day intervals . After four cycles , paclitaxel and carboplatin were discontinued ; bevacizumab-erlotinib treatment was continued until tumor progression . Patients were initially evaluated for response after completion of two treatment cycles ; re-evaluations occurred every 6 weeks thereafter . RESULTS Forty-nine of 60 patients ( 82 % ) completed four cycles of therapy , and 44 patients ( 73 % ) subsequently received maintenance bevacizumab and erlotinib . Thirty-two patients ( 53 % ) had major responses to treatment ; an additional 18 patients had stable disease . After a median follow-up of 19 months , the median progression-free survival time was 8 months , with 38 % of patients progression free at 1 year . The median survival time and 2-year overall survival rate were 12.6 months and 27 % , respectively . Treatment was generally well tolerated , with a toxicity profile as predicted based on the known toxicities of each treatment component . CONCLUSIONS Empiric treatment with paclitaxel , carboplatin , bevacizumab , and erlotinib is effective and well tolerated as first-line treatment for patients with CUP . Further development of this regimen is warranted BACKGROUND To evaluate the efficacy and toxicity of a chemotherapy strategy based on histological differentiation , for patients with carcinoma of unknown primary site . PATIENTS AND METHODS Forty-eight patients were prospect ively included in the trial . Thirty patients with poorly-differentiated carcinoma or poorly-differentiated adenocarcinoma ( group A ) received a combination of cisplatin and etoposide .  Patients with a responsive or stable disease after two cycles received the same regimen plus bleomycin , ifosfamide and G-CSF .  Eighteen patients with well- or moderately-differentiated carcinoma ( group B ) received cisplatin , continuous infusion 5-fluorouracil ( 5-FU ) and alpha-interferon . Treatment was maintained in case of response or stable disease for up to six cycles . RESULTS The overall response rate ( RR ) for the entire group is 43 % ( 95 % confidence interval ( CI ) : 35.9%-50.1 % ) : seven CR and five PR in group A ( RR = 40 % ) and six CR and two PR in group B ( RR = 44 % ) . Grade 4 leucopenia was observed in 22 ( 46 % ) patients and sepsis in 3 ( 6 % ) . Median survival is 9.4 months ( range 5 - 13.7 months ) and 16.1 months ( range 11.8 20.3 months ) , respectively . CONCLUSIONS This chemotherapy strategy is one way to achieve high response rates , particularly for patients with well- or moderately-differentiated adenocarcinoma usually considered poorly chemosensitive Introduction . Taxane/platinum combinations exhibit synergistic cytotoxicity and activity against a broad range of solid tumours . We sought to optimise the regimen as a suitable outpatient palliative treatment for cancer of unknown primary ( CUP ) . Patients and methods . Eligible CUP patients with adenocarcinoma or poorly differentiated carcinoma , performance status of 0 - 2 , adequate organ function and assessable disease were treated with docetaxel 75 mg/m2 and carboplatin at an area under the concentration time-curve ( AUC ) of 5 , both as 30-minute intravenous infusions , every three weeks . Patients with isolated axillary adenopathy , squamous cell cervical or inguinal adenopathy and PSA or germ-cell serum tumour markers were excluded . Results . Forty-seven patients entered the trial , 24 with predominantly nodal disease or non-mucinous peritoneal carcinomatosis ( favourable risk ) and 23 with visceral metastases ( unfavourable risk ) . A median of 6 cycles of chemotherapy were administered , with relative dose intensities of both drugs > 90 % . Response rates were 32 % ( 46 % in favourable risk , 17 % in unfavourable ) , comparable to the activity of paclitaxel/platinum regimes , though complete remissions were seen only in favourable risk patients . Granulocyte-colony stimulating factor support was used in a third of treatment cycles . Toxicity was mild and manageable , with grade 3–4 neutropenia in 26 % of patients , febrile neutropenia in 7 % and severe non-hematologic side-effects in less than 8 % of patients . No toxic deaths or severe neurotoxicity were seen . Median time to progression ( TTP ) and overall survival ( OS ) were 5.5 and 16.2 months respectively . Survival was driven mainly by favourable-risk patients ( 22.6 months ) , as those with visceral metastases had a poor median survival of only 5.3 months . Good performance status and low-volume disease predicted for superior outcome , while docetaxel relative dose-intensity was a positive prognosticator only in favourable-risk patients . Conclusions . One-hour docetaxel/carboplatin is a convenient , safe and effective outpatient palliative treatment for CUP patients , providing meaningful survival prolongation only in favourable-risk patients . Insights in the molecular biology of CUP are needed for the development of targeted therapeutic manipulations of malignant resistance and progression BACKGROUND The purpose of this study was to determine the long-term follow-up on survival of patients with carcinoma of unknown primary site treated with taxane-based chemotherapy in a multicenter community-based setting . PATIENTS AND METHODS Patients were treated with three sequential phase II trials between 1995 and 1998 as follows : Study I : paclitaxel 200 mg/m2 intravenously ( i.v . ) Day 1 , carboplatin AUC = 6 i.v . Day 1 , and oral etoposide 50 mg daily alternating with 100 mg daily days 1 - 10 every 3 weeks ; Study II : docetaxel 75 mg/m2 i.v . Day 1 , cisplatin 75 mg/m2 i.v . Day 1 , repeated every 3 weeks ; Study III : docetaxel 65 mg/m2 i.v . Day 1 , carboplatin AUC 6 i.v . Day 1 , repeated every 3 weeks . A total of 144 patients ( 71 on Study I , 26 on Study II , 47 on Study III ) were treated ( 45 % had well differentiated carcinoma , 48 % had poorly differentiated carcinomas , and 6 % poorly differentiated neuroendocrine tumors ) . The majority of the patients had multiple sites of metastatic disease . RESULTS Thirty-six percent of all evaluable patients responded to therapy ( 27 % partial and 9 % complete responses ) . The median survival was 10 months with 1- , 2- , 3- , and 4-year survivals of 42 % , 22 % , 17 % , and 17 % , respectively . Follow-up ranges from 11 to 50 months . Women survived significantly longer than men . Thirty-one patients remain alive and 14 are progression-free . The primary toxicity was leukopenia with the carboplatin regimens and nausea and vomiting with the cisplatin regimen . A review of the survival of several large previously reported series of patients was compared to results after taxane-based chemotherapy . A compelling argument is made that chemotherapy is superior to best supportive care alone and that taxane-based chemotherapy is superior to other forms of chemotherapy . However , prospect i ve r and omized trials will be necessary to definitively demonstrate the superiority of this treatment compared to other therapies for these patients . CONCLUSION Taxane-based chemotherapy for patients with carcinoma of unknown primary site appears to be clinical ly beneficial and is associated with long-term survival for a minority of patients at 2- , 3- , and 4-year follow-up Abstract . Background : Docetaxel ( Taxotere ) and cisplatin are two of the most active single agents used in the treatment of solid tumors . We examined the feasibility of using a combination of docetaxel and cisplatin for the treatment of unknown primary carcinoma in order to prepare a larger scale prospect i ve study . Methods : Eligible patients were aged 18 to 75 years , with an Eastern Cooperative Oncology Group ( ECOG ) performance status of 2 or less and a life expectancy of 8 weeks or more , and had been diagnosed as having unknown primary carcinoma by the required examinations . Patients were not permitted to have received prior chemotherapy and had to have measurable lesions . Docetaxel ( 60 mg/m2 ) was given intravenously over a 1-h period immediately before cisplatin ( 80 mg/m2 ) , which was given intravenously over a 2-h period , every 3 weeks . Premedication included dexamethasone , granisetron , and st and ard hyperhydration . Results : Twenty-six treatment courses in five patients were tested according to the protocol and feasibility was assessed . Adverse events observed incldued grade 4 neutropenia , leukopenia , grade 3 nausea/vomiting , grade 2 diarrhea , and mucositis . These adverse events were well tolerated , reversible , and manageable . Doses were not reduced and all injections were given or their due date without any delay in all patients . Four patients achieved a partial response and one had stable disease . Conclusion : Treatment of patients with unknown primary carcinoma with a combination of docetaxel and cisplatin is feasible . Conduct of a phase II trial of this regimen is warranted Carcinoma of unknown primary site remains a common clinical diagnosis , accounting for between 5 and 10 % of all cancer patients . Numerous combination chemotherapy regimens have been used in the management of carcinoma of unknown primary site , result ing in response rates of 0–48 % . We present the results of a single centre phase II study of the use of the combination of mitomycin C ( 7 mg m−2 on day 1 of cycles 1 , 3 and 5 ) cisplatin ( 60 mg m−2 on day 1 ) and continuous infusion 5-fluorouracil ( 300 mg m−2 daily ) , MCF , delivered as a 21-day cycle , in patients with carcinoma of unknown primary site . Thirty-one patients with a diagnosis of carcinoma of unknown primary site were treated in Aberdeen Royal Infirmary between 1997 and 2001 with MCF  . In total , 136 cycles of MCF were delivered ( median of 5 cycles per patient ) . Toxicity was acceptable , with 19 % grade 3 or 4 neutropenia , 16 % grade 3 or 4 thrombocytopenia and 13 % grade 3 or 4 nausea and vomiting . No cases of neutropenic sepsis were seen and there were no treatment-related deaths , however , six patients developed thrombotic complications . The overall response rate was 27 % ( CR 3 % ; PR 23 % ) . Median time to progression was 3.4 months ( 95 % CI 1.1–5.6 months ) and median overall survival was 7.7 months ( 95 % CI 5.7–9.8 months ) . Survival at 1 year was 28 % , and at 2 years , 10 % . MCF is a tolerable regimen with comparable toxicity , response rates and survival data to most platinum-based combination chemotherapy regimens in use for this devastating disease Cancer of unknown primary site 
    Output:
    
agent
***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: Platinum/taxane combinations are widely used in patients with carcinoma of unknown primary ( CUP ) , yielding response rates of 30 % and median overall survival of 9–11 months in selected patients . Yet these combinations have not been subject to a r and omised trial to overcome selection bias , a major problem in CUP . We r and omised 92 patients to either paclitaxel/carboplatin ( arm A ) or the non-platinum non-taxane regimen gemcitabine/vinorelbine ( arm B ) . The primary endpoint was rate of practicability as defined : application of ⩾2 cycles of therapy ( 1 ) with a maximal delay of 1 week ( 2 ) and survival of ⩾8 months ( 3 ) . Practicability was shown in 52.4 % ( 95 % CI 36–68 % ) in arm A and in 42.2 % ( 95 % CI 28–58 % ) in arm B , respectively . The median overall survival , 1-year survival -rate and response rate of patients treated in arm A was 11.0 months , 38 , and 23.8 % , arm B 7.0 months , 29 , and 20 % . In conclusion , the paclitaxel/carboplatin regimen showed clinical ly meaningful activity in this r and omised trial ( Clinical trial registration number 219 , ‘ Deutsches KrebsStudienRegister ’ , German Cancer Society . INTRODUCTION This phase II trial evaluated the efficacy and toxicity of the combination of paclitaxel , carboplatin , bevacizumab , and erlotinib in the first-line treatment of patients with carcinoma of unknown primary site ( CUP ) . METHODS Patients with previously untreated CUP ( adenocarcinoma , poorly differentiated carcinoma , poorly differentiated squamous carcinoma ) without clinical or pathologic characteristics of a well-defined treatable subset were eligible . All patients received paclitaxel , carboplatin , bevacizumab , and erlotinib . Treatment cycles were repeated at 21-day intervals . After four cycles , paclitaxel and carboplatin were discontinued ; bevacizumab-erlotinib treatment was continued until tumor progression . Patients were initially evaluated for response after completion of two treatment cycles ; re-evaluations occurred every 6 weeks thereafter . RESULTS Forty-nine of 60 patients ( 82 % ) completed four cycles of therapy , and 44 patients ( 73 % ) subsequently received maintenance bevacizumab and erlotinib . Thirty-two patients ( 53 % ) had major responses to treatment ; an additional 18 patients had stable disease . After a median follow-up of 19 months , the median progression-free survival time was 8 months , with 38 % of patients progression free at 1 year . The median survival time and 2-year overall survival rate were 12.6 months and 27 % , respectively . Treatment was generally well tolerated , with a toxicity profile as predicted based on the known toxicities of each treatment component . CONCLUSIONS Empiric treatment with paclitaxel , carboplatin , bevacizumab , and erlotinib is effective and well tolerated as first-line treatment for patients with CUP . Further development of this regimen is warranted BACKGROUND To evaluate the efficacy and toxicity of a chemotherapy strategy based on histological differentiation , for patients with carcinoma of unknown primary site . PATIENTS AND METHODS Forty-eight patients were prospect ively included in the trial . Thirty patients with poorly-differentiated carcinoma or poorly-differentiated adenocarcinoma ( group A ) received a combination of cisplatin and etoposide .  Patients with a responsive or stable disease after two cycles received the same regimen plus bleomycin , ifosfamide and G-CSF .  Eighteen patients with well- or moderately-differentiated carcinoma ( group B ) received cisplatin , continuous infusion 5-fluorouracil ( 5-FU ) and alpha-interferon . Treatment was maintained in case of response or stable disease for up to six cycles . RESULTS The overall response rate ( RR ) for the entire group is 43 % ( 95 % confidence interval ( CI ) : 35.9%-50.1 % ) : seven CR and five PR in group A ( RR = 40 % ) and six CR and two PR in group B ( RR = 44 % ) . Grade 4 leucopenia was observed in 22 ( 46 % ) patients and sepsis in 3 ( 6 % ) . Median survival is 9.4 months ( range 5 - 13.7 months ) and 16.1 months ( range 11.8 20.3 months ) , respectively . CONCLUSIONS This chemotherapy strategy is one way to achieve high response rates , particularly for patients with well- or moderately-differentiated adenocarcinoma usually considered poorly chemosensitive Introduction . Taxane/platinum combinations exhibit synergistic cytotoxicity and activity against a broad range of solid tumours . We sought to optimise the regimen as a suitable outpatient palliative treatment for cancer of unknown primary ( CUP ) . Patients and methods . Eligible CUP patients with adenocarcinoma or poorly differentiated carcinoma , performance status of 0 - 2 , adequate organ function and assessable disease were treated with docetaxel 75 mg/m2 and carboplatin at an area under the concentration time-curve ( AUC ) of 5 , both as 30-minute intravenous infusions , every three weeks . Patients with isolated axillary adenopathy , squamous cell cervical or inguinal adenopathy and PSA or germ-cell serum tumour markers were excluded . Results . Forty-seven patients entered the trial , 24 with predominantly nodal disease or non-mucinous peritoneal carcinomatosis ( favourable risk ) and 23 with visceral metastases ( unfavourable risk ) . A median of 6 cycles of chemotherapy were administered , with relative dose intensities of both drugs > 90 % . Response rates were 32 % ( 46 % in favourable risk , 17 % in unfavourable ) , comparable to the activity of paclitaxel/platinum regimes , though complete remissions were seen only in favourable risk patients . Granulocyte-colony stimulating factor support was used in a third of treatment cycles . Toxicity was mild and manageable , with grade 3–4 neutropenia in 26 % of patients , febrile neutropenia in 7 % and severe non-hematologic side-effects in less than 8 % of patients . No toxic deaths or severe neurotoxicity were seen . Median time to progression ( TTP ) and overall survival ( OS ) were 5.5 and 16.2 months respectively . Survival was driven mainly by favourable-risk patients ( 22.6 months ) , as those with visceral metastases had a poor median survival of only 5.3 months . Good performance status and low-volume disease predicted for superior outcome , while docetaxel relative dose-intensity was a positive prognosticator only in favourable-risk patients . Conclusions . One-hour docetaxel/carboplatin is a convenient , safe and effective outpatient palliative treatment for CUP patients , providing meaningful survival prolongation only in favourable-risk patients . Insights in the molecular biology of CUP are needed for the development of targeted therapeutic manipulations of malignant resistance and progression BACKGROUND The purpose of this study was to determine the long-term follow-up on survival of patients with carcinoma of unknown primary site treated with taxane-based chemotherapy in a multicenter community-based setting . PATIENTS AND METHODS Patients were treated with three sequential phase II trials between 1995 and 1998 as follows : Study I : paclitaxel 200 mg/m2 intravenously ( i.v . ) Day 1 , carboplatin AUC = 6 i.v . Day 1 , and oral etoposide 50 mg daily alternating with 100 mg daily days 1 - 10 every 3 weeks ; Study II : docetaxel 75 mg/m2 i.v . Day 1 , cisplatin 75 mg/m2 i.v . Day 1 , repeated every 3 weeks ; Study III : docetaxel 65 mg/m2 i.v . Day 1 , carboplatin AUC 6 i.v . Day 1 , repeated every 3 weeks . A total of 144 patients ( 71 on Study I , 26 on Study II , 47 on Study III ) were treated ( 45 % had well differentiated carcinoma , 48 % had poorly differentiated carcinomas , and 6 % poorly differentiated neuroendocrine tumors ) . The majority of the patients had multiple sites of metastatic disease . RESULTS Thirty-six percent of all evaluable patients responded to therapy ( 27 % partial and 9 % complete responses ) . The median survival was 10 months with 1- , 2- , 3- , and 4-year survivals of 42 % , 22 % , 17 % , and 17 % , respectively . Follow-up ranges from 11 to 50 months . Women survived significantly longer than men . Thirty-one patients remain alive and 14 are progression-free . The primary toxicity was leukopenia with the carboplatin regimens and nausea and vomiting with the cisplatin regimen . A review of the survival of several large previously reported series of patients was compared to results after taxane-based chemotherapy . A compelling argument is made that chemotherapy is superior to best supportive care alone and that taxane-based chemotherapy is superior to other forms of chemotherapy . However , prospect i ve r and omized trials will be necessary to definitively demonstrate the superiority of this treatment compared to other therapies for these patients . CONCLUSION Taxane-based chemotherapy for patients with carcinoma of unknown primary site appears to be clinical ly beneficial and is associated with long-term survival for a minority of patients at 2- , 3- , and 4-year follow-up Abstract . Background : Docetaxel ( Taxotere ) and cisplatin are two of the most active single agents used in the treatment of solid tumors . We examined the feasibility of using a combination of docetaxel and cisplatin for the treatment of unknown primary carcinoma in order to prepare a larger scale prospect i ve study . Methods : Eligible patients were aged 18 to 75 years , with an Eastern Cooperative Oncology Group ( ECOG ) performance status of 2 or less and a life expectancy of 8 weeks or more , and had been diagnosed as having unknown primary carcinoma by the required examinations . Patients were not permitted to have received prior chemotherapy and had to have measurable lesions . Docetaxel ( 60 mg/m2 ) was given intravenously over a 1-h period immediately before cisplatin ( 80 mg/m2 ) , which was given intravenously over a 2-h period , every 3 weeks . Premedication included dexamethasone , granisetron , and st and ard hyperhydration . Results : Twenty-six treatment courses in five patients were tested according to the protocol and feasibility was assessed . Adverse events observed incldued grade 4 neutropenia , leukopenia , grade 3 nausea/vomiting , grade 2 diarrhea , and mucositis . These adverse events were well tolerated , reversible , and manageable . Doses were not reduced and all injections were given or their due date without any delay in all patients . Four patients achieved a partial response and one had stable disease . Conclusion : Treatment of patients with unknown primary carcinoma with a combination of docetaxel and cisplatin is feasible . Conduct of a phase II trial of this regimen is warranted Carcinoma of unknown primary site remains a common clinical diagnosis , accounting for between 5 and 10 % of all cancer patients . Numerous combination chemotherapy regimens have been used in the management of carcinoma of unknown primary site , result ing in response rates of 0–48 % . We present the results of a single centre phase II study of the use of the combination of mitomycin C ( 7 mg m−2 on day 1 of cycles 1 , 3 and 5 ) cisplatin ( 60 mg m−2 on day 1 ) and continuous infusion 5-fluorouracil ( 300 mg m−2 daily ) , MCF , delivered as a 21-day cycle , in patients with carcinoma of unknown primary site . Thirty-one patients with a diagnosis of carcinoma of unknown primary site were treated in Aberdeen Royal Infirmary between 1997 and 2001 with MCF  . In total , 136 cycles of MCF were delivered ( median of 5 cycles per patient ) . Toxicity was acceptable , with 19 % grade 3 or 4 neutropenia , 16 % grade 3 or 4 thrombocytopenia and 13 % grade 3 or 4 nausea and vomiting . No cases of neutropenic sepsis were seen and there were no treatment-related deaths , however , six patients developed thrombotic complications . The overall response rate was 27 % ( CR 3 % ; PR 23 % ) . Median time to progression was 3.4 months ( 95 % CI 1.1–5.6 months ) and median overall survival was 7.7 months ( 95 % CI 5.7–9.8 months ) . Survival at 1 year was 28 % , and at 2 years , 10 % . MCF is a tolerable regimen with comparable toxicity , response rates and survival data to most platinum-based combination chemotherapy regimens in use for this devastating disease Cancer of unknown primary site 
    Output:
    