Paclitaxel and carboplatin vs gemcitabine and vinorelbine in patients with adeno- or undifferentiated carcinoma of unknown primary: a randomised prospective phase II trial Paclitaxel/carboplatin plus bevacizumab/erlotinib in the first-line treatment of patients with carcinoma of unknown primary site. Carcinoma of an unknown primary site: a chemotherapy strategy based on histological differentiation--results of a prospective study. Docetaxel and carboplatin combination chemotherapy as outpatient palliative therapy in carcinoma of unknown primary: A multicentre Hellenic Cooperative Oncology Group phase II study Taxane-based chemotherapy for patients with carcinoma of unknown primary site. Unknown primary carcinoma: a feasibility assessment of combination chemotherapy with cisplatin and docetaxel A phase II study of mitomycin C, cisplatin and continuous infusion 5-fluorouracil (MCF) in the treatment of patients with carcinoma of unknown primary site Gemcitabine and carboplatin in carcinoma of unknown primary site: a phase 2 Adelaide Cancer Trials and Education Collaborative study Carboplatin, doxorubicin and etoposide in the treatment of tumours of unknown primary site Irinotecan plus carboplatin for patients with carcinoma of unknown primary site A phase II study of cisplatin, etoposide and gemcitabine in an unfavourable group of patients with carcinoma of unknown primary site. A Phase II Study of Carboplatin and Paclitaxel in Adenocarcinoma of Unknown Primary A randomized Phase II trial in patients with carcinoma of an unknown primary site Multicenter phase-II trial of irinotecan plus oxaliplatin [IROX regimen] in patients with poor-prognosis cancer of unknown primary: a hellenic cooperative oncology group study Phase II Trial of Capecitabine and Oxaliplatin in Patients with Adeno- and Undifferentiated Carcinoma of Unknown Primary Paclitaxel, cisplatin and gemcitabine in treatment of carcinomas of unknown primary site, a phase II study Gemcitabine, carboplatin, and paclitaxel for patients with carcinoma of unknown primary site: a Minnie Pearl Cancer Research Network study. Methodological index for non‐randomized studies (MINORS): development and validation of a new instrument Combination of Cisplatin‐Doxorubicin‐Cyclophosphamide in Adenocarcinoma of Unknown Primary Site: A Phase II Trial Phase II trial of carboplatin, gemcitabine, and capecitabine in patients with carcinoma of unknown primary site Unknown primary carcinoma: natural history and prognostic factors in 657 consecutive patients. Cisplatin and gemcitabine with either vinorelbine or paclitaxel in the treatment of carcinomas of unknown primary site Gemcitabine and docetaxel as front‐line chemotherapy in patients with carcinoma of an unknown primary site Phase II study of epirubicin, cisplatin and continuous infusion 5-fluorouracil (ECF) for carcinoma of unknown primary site. Paclitaxel/Carboplatin/Etoposide Versus Gemcitabine/Irinotecan in the First-Line Treatment of Patients With Carcinoma of Unknown Primary Site: A Randomized, Phase III Sarah Cannon Oncology Research Consortium Trial Cisplatin in combination with either gemcitabine or irinotecan in carcinomas of unknown primary site: results of a randomized phase II study--trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). Carboplatin plus paclitaxel in unknown primary carcinoma: a phase II Hellenic Cooperative Oncology Group Study. A randomised study of protracted venous infusion of 5-fluorouracil (5-FU) with or without bolus mitomycin C (MMC) in patients with carcinoma of unknown primary. Safety and Efficacy of a Combination of Docetaxel and Cisplatin in Patients With Unknown Primary Cancer
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 ( CUP ) represents up to 5 % of all cancer diagnoses and is associated with poor survival . We have performed a prospect i ve multicentre phase 2 trial to evaluate efficacy and toxicity of the combination of gemcitabine ( G ) and carboplatin ( C ) for patients with CUP . Patients with histologically confirmed metastatic carcinoma in which the primary site of cancer was not evident after prospect ively design ated investigation and who had ECOG performance status 0–2 were treated with G 1000 mg m−2 intravenously ( i.v . ) days 1 and 8 , and C AUC 5 i.v . on day 8 every 3 weeks to a maximum of nine cycles . The primary end points were response rate , and toxicity , with secondary end points of progression-free survival and overall survival . Fifty-one ( 23 male , 27 female ) patients were enrolled ( one patient ineligible ) , with a median age of 69 years ( range 41–83 years ) . Fifty patients were evaluable for  toxicity  and 46 patients were evaluable for efficacy  . The overall response rate to the GC regimen was 30.5 % . With a median follow-up of 24 months , the median progression-free survival was 18 weeks ( 4.2 months ) and the median overall survival was 34 weeks ( 7.8 months ) . The frequency of grade 3 or 4 toxicity was low . Nausea/vomiting was the most common side effect , but was usually only mild in severity . Uncomplicated neutropenia ( 14 % ) , thrombocytopenia ( 10 % ) and anaemia ( 8 % ) were the most common causes of grade 3–4 toxicity . The regimen was very well tolerated , particularly in the elderly . The GC regimen is an active regimen in CUP with excellent tolerability and should be considered particularly for elderly patients with CUP The aim of this study was to assess the activity and toxicity of a platinum-based treatment on a group of patients with unknown primary tumours ( UPTs ) . Patients with a diagnosis of UPT underwent a st and ard diagnostic procedure . Treatment was started within 2 weeks from diagnosis and consisted of carboplatin 400 mg m−2 day 1 , doxorubicin 50 mg m−2 day 1 , etoposide 100 mg m−2 days 1–3 , every 21 days . Response was evaluated after three courses and treatment continued in case of objective response ( OR ) or symptom control . A total of 102 patients were eligible . The median age was 59 years , sex male/female 54/48 , histology was mainly adenocarcinoma or poorly differentiated carcinoma . Nodes , bone , liver and lung were the most frequently involved sites . In all , 79 patients received at least three courses of treatment ; 26 patients received six courses or more . Six complete responses and 21 partial responses were observed , for a total of 27 of 102 ORs or 26.5 % ( 95 % confidence interval 18.2–36.1 % ) . The median survival was 9 months and median progression-free survival was 4 months . Toxicity was moderate to severe , with 57.8 % of patients experiencing grade III – IV haematological toxicity , mainly leucopenia . The regimen employed has shown activity in tumours of unknown primary site , but was associated with significant toxicity . Such toxicity may be considered unjustified , given the large proportion of patients with tumours not likely to respond . Efforts should therefore be addressed to identify predictors of response to chemotherapy , thus limiting aggressive treatment to those patients who could benefit from it Carcinoma of unknown primary site ( CUP ) is rarely encountered in clinical practice and optimal chemotherapy has not yet been established . This phase II study was conducted to evaluate the efficacy and toxicity of combined irinotecan+carboplatin therapy in chemotherapy-naive patients with CUP .  Irinotecan was administered at 60 mg m−2 as a 90-min intravenous infusion on days 1 , 8 and 15 . Carboplatin was administered at an area-under-the curve of 5 mg ml−1 min as a 60-min intravenous infusion on day 1 . This cycle was repeated every 28 days for up to six cycles . Forty-five patients were enrolled in the study . An intent-to-treat analysis revealed an objective response rate to the treatment of 41.9 % ( 95 % confidence interval , 27.0–57.9 % ) . The median time to progression was 4.8 months and the median survival was 12.2 months . The 1- and 2-year survival rates were 44 and 27 % , respectively . The most frequent grade 3 or more severe adverse events were leukopaenia ( 21 % ) , neutropaenia ( 33 % ) , anaemia ( 25 % ) and thrombocytopaenia ( 20 % ) . Thus , the combination of irinotecan plus carboplatin was found to be active in patients with CUP . Therefore , the regimen may be one of the potentially available chemotherapeutic options for community st and ard of care in patients with a good performance status BACKGROUND The aim of this phase II study was to determine toxicity , response rate , time to progression , and overall survival of cisplatin , etoposide and gemcitabine in patients with carcinoma of unknown primary tumour site . PATIENTS AND METHODS Thirty patients with no previous chemotherapy and not belonging to a treatable group were treated with cisplatin 70 mg/m(2 ) on day 1 , etoposide 70 mg/m(2 ) on days 1 and 2 , and gemcitabine 700 mg m(2 ) on days 1 and 8 , administered every 3 weeks . Stable or responding patients received a maximum of eight cycles . Twenty patients ( 67 % ) had more than three affected sites , and 25 patients ( 84 % ) had adenocarcinomas . RESULTS Overall response rate was 36.6 % ( 11 patients ) , including four complete responses ( 13.3 % ) and seven partial responses ( 23.3 % ) , with a 95 % confidence interval of 19.9 - 56 . Median survival was 7.21 months and eight patients remained alive for > 1 year . Myelosuppression was the most important toxicity , with grade 3 - 4 neutropenia in 18 patients ( 60 % ) in 32 % of the cycles : eight patients had neutropenic fever and 10 patients had thrombopenia in 11 % of cycles . No non-haematological grade 4 toxicity occurred . CONCLUSIONS Cisplatin , etoposide and gemcitabine is an active combination , inducing objective responses in a subset of heavily advanced disease patients with carcinoma of unknown primary site . The role of adding gemcitabine to cisplatin and etoposide remains to be resolved as to the best schedule to diminish toxicity for the three-drug combination Background : Cisplatin-based combination chemotherapy is commonly used in the treatment of carcinoma of unknown primary site .  Paclitaxel has shown promising activity as a single agent in a number of malignancies . This study was conducted to evaluate the efficacy and toxicity of combination carboplatin and paclitaxel in patients with adenocarcinoma of unknown primary site ( ACUP ) . Methods : Twenty-two patients with ACUP were enrolled in the study . Patients were treated with 200 mg/m2 paclitaxel intravenously ( IV ) over 3 hours followed by carboplatin IV with a targeted plasma area under the curve ( AUC ) of 5 mg/h/mL. Results : A total of 73 treatment courses were administered with a median of 5 courses per patient . Five of the 22 registered patients had a major response for an objective response rate of 23 % ( 90 % confidence interval [ CI ] , 0.11–0.40 ) by intention-to-treat analysis . The median response duration was 4.1 months ( 90 % CI , 3.6–7.1 ) . The median survival time was 6.5 months ( 90 % CI , 5.5–10.1 ) and the 1-year survival rate was 27 % ( 90 % CI , 0.11–0.42 ) . The major toxicity observed was neutropenia , with grade 3–4 neutropenia occurring in 3 patients ( 14 % ) . There were no treatment-related deaths . Conclusions : The combination of carboplatin and paclitaxel is a tolerable and moderately active regimen in ACUP Current therapy for patients with carcinoma of an unknown primary site ( CUP ) is inadequate . To develop less toxic and more effective therapies for patients with CUP , a multicenter , r and omized , Phase II study was conducted . Patients with CUP received either carboplatin and etoposide ( CE ) or a combination of paclitaxel , 5‐fluorouracil , and leucovorin ( TFL ) Background Cancer of unknown primary ( CUP ) lacks established therapy although it affects 3 % of cancer patients . We evaluated the irinotecan – oxaliplatin combination ( IROX regimen ) in previously untreated patients with non-favorable subsets of unknown primary carcinomas . Methods This was a multicenter phase-II trial . Protocol treatment consisted of oxaliplatin 80 mg/m2 followed by irinotecan 160 mg/m2 administered every 3 weeks . The primary end points were response rate and toxicity , and secondary end points were time to progression and survival . Results Forty-seven patients with liver , bone or multiple visceral metastases entered into the trial and received a median 6 chemotherapy cycles ( 1–11 ) . The regimen was very well tolerated with one febrile neutropenia case and six cases with diarrhea grade 3 ( 16 % ) . In intent-to-treat analysis the tumor response rate was 13 % ( 95 % CI = 4.8–25.7 % ) and 12 patients ( 27 % , 95%CI 13.9–40.4 % ) had at least 4 months ’ duration of disease stabilization . The median time to progression was 2.7 months and the median survival was 9.5 months , with 40 % of patients alive at 1 year . Conclusions The IROX regimen demonstrated similar efficacy and a favorable toxicity profile compared to other more toxic chemotherapy combinations in patients with poor-prognosis CUP Background : Carcinomas of unknown primary ( CUP ) account for approximately 2–5 % of all cancer diagnoses . Except for some subsets with favorable prognosis , for most of these patients treatment options are limited , and no st and ard first-line regimen has been identified . We performed a phase II study with oxaliplatin ( OX ) and capecitabine ( CAP ) as first-line treatment for patients with histo-or cytologically proven adeno- or undifferentiated CUP . Patients and Methods : Protocol treatment in this multicenter trial consisted of CAP 1,000 mg/m2 twice daily orally ( days 1–14 ) and OX 130 mg/m2 intravenously ( day 1 ) , repeated every 21 days at a maximum of 6 cycles . The primary endpoint was the response rate ( RR ) . Secondary endpoints were progression-free survival ( PFS ) , overall survival ( OS ) , and safety . Results : 51 patients with CUP ( 71 % with poorly differentiated adenocarcinoma ; 41 % ECOG performance status ( PS ) 0 , 39 % PS 1 , 10 % PS 2 , 55 % with elevated lactate dehydrogenase ( LDH ) , and 39 % with liver metastases ) were enrolled in this study . We observed an objective RR of 11.7 % and a median PFS of 2.5 months as well as an OS of 7.5 months with a good toxicity profile . Conclusion : CAP/OX did not reach higher RR compared to a st and ard regimen with paclitaxel/carboplatin , which discourages further investigation of this schedule in CUP Abstract Background . The present study was conducted to evaluate the efficacy and toxicity of a combination of paclitaxel , cisplatin and gemcitabine in patients with carcinoma of unknown primary site ( CUP ) . Patients and methods . Patients with CUP , ECOG performance status 0–1 and age between 18 and 65 years old were treated with paclitaxel 175 mg/m2 day 1 , cisplatin 75 mg/m2 day 1 and gemcitabine 1000 mg/m2 day 1 and 8 in a three-week schedule . Results . Ninety-eight patients were enrolled between 1998 and 2008 . Ninety-one patients had target lesions according to the RECIST guidelines . The overall response rate was 42.9 % ( 39 patients ) , including five complete responses ( 5.5 % ) and 34 partial responses ( 37.4 % ) . The median survival time was 10.7 months , and the survival rates at one and two years were 42 % and 14 % , respectively . The most frequent grade 3 or more adverse events were neutropenia and thrombocytopenia . There were 3 treatment-related deaths . Conclusions . Combination of paclitaxel , cisplatin and gemcitabine is an active regimen in patients with CUP with response and survival rates at least similar to other platinum- and taxane-containing regimens . The treatment was well tolerated by most patients although neutropenia and thrombocytopenia were relatively common . The present regimen represents an attractive regimen in younger CUP patients with a good performance status PURPOSE To evaluate the efficacy and toxicity of the novel chemotherapy combination that includes gemcitabine , carboplatin , and paclitaxel in the treatment of patients with carcinoma of unknown primary site . PATIENTS AND METHODS One hundred twenty patients were treated with the following regimen , administered every 21 days for a planned four courses : gemcitabine 1,000 mg/m(2 ) intravenously ( i.v . ) on days 1 and 8 , carboplatin at an estimated area under the concentration-time curve of 5 mg min/mL i.v . on day 1 , and paclitaxel 200 mg/m(2 ) i.v . on day 1 . After four courses , stable and responding patients were given weekly paclitaxel 70 mg/m(2 ) i.v . for 6 weeks for three 8-week courses . All patients had relatively poor prognostic features . Sixty-three patients had well-differentiated adenocarcinoma , 56 patients had poorly differentiated carcinoma , and 104 patients had performance status of 0 or 1 . RESULTS Twenty-eight ( 25 % ) of 113 assessable patients ( 95 % confidence interval , 22 % to 30 % ) had major objective responses to treatment . Response rates were similar in the two major histologic types . Response rate did not seem to be improved by continued therapy with weekly paclitaxel . The median progression-free survival time was 6 months . Median survival for the entire group was 9 months , and the actuarial survival at 1 and 2 years was 42 % and 23 % , respectively . CONCLUSION Combination chemotherapy with gemcitabine , carboplatin , and paclitaxel followed by weekly paclitaxel is an active and tolerable treatment for patients with carcinoma of unknown primary site . The survival seen in this poor-prognosis group of patients in this multicenter community-based trial is notable and similar to other taxane-based regimens for these patients . Study of additional combinations or sequences of newer drugs , as well as the exploration of targeted biologic agents for patients with an identified target in their tumors , is warranted Background : Because of specific method ological difficulties in conducting r and omized trials , surgical research remains dependent predominantly on observational or non‐r and omized studies . Few vali date d instruments are available to determine the method ological quality of such studies either from the reader 's perspective or for the purpose of meta‐ analysis . The aim of the present study was to develop and vali date such an instrument & NA ; The purpose of this report is to evaluate toxicity , response , and survival of the cyclophosphamide‐doxorubicin‐cisplatin ( CAP ) chemotherapy regimen in patients with adenocarcinoma of unknown primary site ( ACUP ) . Twenty‐two patients with ACUP were eligible for this study between June 1992 and April 1999 . There were 13 men ( 59 % ) and 9 women ( 41 % ) with a median age of 53.5 years ( range : 29–78 years ) . Lung ( seven ) , liver ( six ) , vertebral bone site ( six ) , and abdominal nodes ( six ) were the most common metastatic sites . Treatment consisted of doxorubicin 50 mg/m2 , cyclophosphamide 1,000 mg/m2 , and cisplatin 100 mg/m2 ( CAP ) , administered every 3 weeks ; a total of six courses were planned . Twenty‐two patients were assessable for toxicity and 20 patients were assessable for response . Grade III to IV neutropenia was observed in 14 patients ( 64 % ) ; febrile neutropenia occurred in 6 patients ( 27 % ) and in 10 cycles ( 12.5 % ) . Grade III to IV anemia and thrombocytopenia were found in 12 ( 54.5 % ) and 9 patients ( 41 % ) , respectively . Grade III to IV nausea and vomiting was observed in 9 patients ( 41 % ) . Ten patients , 50 % of the assessable population , obtained an objective response , including 3 complete ( 15 % ) and 7 partial ( 35 % ) responses . The median response duration was 3.9 months ( range : 0.5–13.3 months ) . One patient ( 5 % ) had stable disease and 5 patients ( 25 % ) had progressive disease . The median overall survival and the median time to progression were 10.7 months ( range : 0.4–56.9 months ) and 8.8 months ( range : 6.6–16.5 months ) , respectively . The CAP regimen in patients with ACUP had significant activity . This chemotherapy regimen induced a high level of grade III to IV toxicities and could not be considered as a treatment of reference . However , the emergence of long‐term survivors among responder patients highlighted the need to search for an active treatment for patients with ACUP The purpose s of this study were to evaluate efficacy and toxicity of the combination of carboplatin , gemcitabine , and capecitabine in patients with carcinoma of unknown primary site ( CUP ) PURPOSE To evaluate the natural history , vali date previous observations , and identify prognostic factors in patients with unknown primary carcinoma ( UPC ) . PATIENTS AND METHODS Nine hundred twenty-seven consecutive patients referred to the M.D. And erson Cancer Center with a preliminary diagnosis of UPC were prospect ively identified . A st and ardized evaluation narrowed the study population to 657 patients with UPC . All data were recorded and computerized for storage , retrieval , and analysis . The primary end point for the study was survival , which was calculated from the first day of patient registration . Survival curves were estimated using the Kaplan-Meier method and compared using the Cox-Mantel log-rank test . To identify important prognostic factors , univariate and multivariate analyses were conducted . RESULTS The demographics of the UPC patient population mirrored those of the general population of patients referred to our cancer center except for an excess of men among the UPC patients . Most patients had histologic or cytologic evidence of adenocarcinoma and had more than one organ site metastatically involved . Univariate and multivariate analyses identified numerous important prognostic factors with a significant influence on survival , including sex , number of organ sites involved , specific organ sites involved , and pathologic subtypes . CONCLUSION This study vali date d previously identified important prognostic factors for survival in UPC . Additional variables that had an impact on survival were identified and the complex interaction of the factors was explored . As patient numbers increase , this data base will be able to provide further analyses of patient subsets and potentially relate specific clinical features to the evolving molecular and biochemical underst and ing of these malignancies To date , the st and ard treatment for patients who have carcinoma of unknown primary site has not been established The current study was performed to evaluate the efficacy and toxicity of a noncisplatin‐based chemotherapy regimen combining gemcitabine and docetaxel as front‐line chemotherapy for patients with carcinoma of an unknown primary site Patients with carcinoma of unknown primary site account for up to 15 % of cancer diagnoses but chemotherapy has disappointing response rates and little impact on overall survival [ 1,2 ] . Cisplatin-based regimens are the mainstay of treatment [ 3 ] . The combination of epirubicin , cisplatin and continuous infusion 5-fluorouracil ( 5-FU ) has been shown to be very active and reasonably well tolerated in the treatment of metastatic breast cancer , esophagogastric and pancreatic adenocarcinomas [ 4 , 5 ] . There has been a report of this combination for cancer of unknown primary that suggests further evaluation [ 6 ] Purpose : To compare the results of empiric first-line therapy with paclitaxel/carboplatin/etoposide ( PCE ) versus gemcitabine/irinotecan , both followed by single-agent gefitinib , in patients with carcinoma of unknown primary site . Patients and Methods : Patients with previously untreated carcinoma of unknown primary site were r and omized to receive either PCE or gemcitabine/irinotecan .  Responding and stable patients continued treatment for 4 to 6 cycles . Patients with no evidence of tumor progression at that time received single-agent gefitinib until tumor progression . The trial was design ed to detect an improvement in the 2-year survival rate from 20 % to 30 % . Results : Between September 2003 and July 2008 , 198 patients entered this multicenter , community-based trial . Because of slow accrual , the trial was stopped short of its target accrual of 320 patients . Clinical characteristics were comparable for patients receiving PCE ( N = 93 ) and gemcitabine/irinotecan ( N = 105 ) . PCE and gemcitabine/irinotecan produced similar 2-year survival ( 15 % vs. 18 % ) , median survival ( 7.4 months vs. 8.5 months ) , median progression-free survival ( 3.3 months vs. 5.3 months ) , and response rate ( 18 % vs. 18 % ) . Grade 3/4 neutropenia , thrombocytopenia , anemia , febrile neutropenia , and red blood cells transfusions were more common with PCE ;  diarrhea was more common with gemcitabine/irinotecan . The median duration of gefitinib maintenance was 3 months , suggesting no role as a maintenance therapy in this setting . Discussion : The PCE and gemcitabine/irinotecan regimens have comparable efficacy in the first-line treatment of patients with carcinoma of unknown primary site .  Gemcitabine/irinotecan is the preferable regimen , due to its favorable toxicity profile . However , the moderate efficacy of both regimens underscores the need for novel treatment approaches in this patient population PURPOSE To evaluate the efficacy and toxicity of novel chemotherapy combinations including cisplatin with gemcitabine ( GC ) or irinotecan ( IC ) for patients with carcinomas of an unknown primary site . PATIENTS AND METHODS Eighty patients were r and omly assigned to receive GC or IC .  In the GC arm , chemotherapy consisted of cycles combining gemcitabine 1,250 mg/m2 intravenously ( IV ) on days 1 and 8 , and cisplatin 100 mg/m2 IV on day 1 at 3-week intervals . Patients in the IC arm originally received 3-week cycles of irinotecan 200 mg/m2 IV on day 1 and cisplatin 80 mg/m2 IV on day 1 . After the inclusion of 15 patients in that arm , the toxicity profile required the irinotecan doses to be reduced to 150 mg/m2 per cycle . Independent histologic and radiologic review s were done . RESULTS A total of 78 patients were assessable for efficacy and toxicity . The median number of cycles was four in each arm . Objective responses were observed in 21 patients ( 55 % ) in the GC arm ( 95 % CI , 34 % to 66 % ) and in 15 patients ( 38 % ) in the IC arm ( 95 % CI , 23 % to 54 % ) . Treatment had to be stopped because of toxicity in seven patients in the GC arm and in eight patients in the IC arm . With a median follow-up of 22 months , the median survivals were 8 and 6 months in the GC and IC arms , respectively . CONCLUSION This study demonstrates the activity of both the GC and IC regimens . There was toxicity associated with both regimens . Additional studies of combination chemotherapy regimens are required PURPOSE To evaluate the efficacy of the carboplatin/paclitaxel combination in patients with carcinoma of unknown primary site ( CUP ) . PATIENTS AND METHODS Seventy-seven consecutive CUP patients ( 45 women and 32 men ; median age , 60 years ) were treated with carboplatin at target area under the curve 6 mg/mL/min followed by paclitaxel 200 mg/m(2 ) as a 3-hour infusion and granulocyte colony-stimulating factor from days 5 to 12 . Treatment courses were repeated every 3 weeks to a maximum of eight cycles . Forty-seven patients had adenocarcinomas , 27 had undifferentiated carcinomas , and three had squamous cell carcinomas . Thirty-three patients presented with liver , bone , or multiple organ metastases , 23 with predominantly nodal/pleural disease , and 19 ( 16 women ) with peritoneal carcinomatosis . RESULTS The overall response rate by intent-to-treat analysis was 38.7 % ( 95 % confidence interval , 27.5 % to 49.9 % ) . There were no differences in response between adenocarcinomas and undifferentiated carcinomas , but efficacy varied among clinical subsets . The response rates and median survival times in the three clinical ly defined subsets were 47.8 % and 13 months , respectively , for patients with predominantly nodal/pleural disease , 68.4 % and 15 months , respectively , in women with peritoneal carcinomatosis , and 15.1 % and 10 months , respectively , in patients with visceral or disseminated metastases . Chemotherapy was well-tolerated . CONCLUSION Carboplatin plus paclitaxel combination chemotherapy is effective in patients with predominantly nodal/pleural metastases of unknown primary carcinoma and in women with peritoneal carcinomatosis . However , in patients with liver , bone , or multiple organ involvement , the combination offers limited benefit . The investigation of novel treatment approaches is highly warranted for this group of patients No st and ard regimen has been identified for patients with a carcinoma of unknown primary ( CUP ) . This study compared protracted venous infusion 5-fluorouracil ( PVI 5-FU ) with or without mitomycin C ( MMC ) in patients with CUP in a multicentre , prospect ively r and omised study . 88 patients were r and omised to PVI 5-FU  ( 300 mg/m(2)/day for a maximum of 24 weeks ) + /-MMC ( 7 mg/m(2 ) 6 weekly for four courses ) . The overall response rate was 11.6 % for PVI 5-FU alone compared with 20.0 % for PVI 5-FU plus MMC ( P=0.29 ) . Median failure-free survival ( FFS ) was 4.1 months for PVI 5-FU and 3.6 months for PVI 5-FU plus MMC ( P=0.78 ) with an equivalent overall survival ( OS ) ( 6.6 versus 4.7 months , P=0.60 ) . Symptomatic benefit was observed in most patients in each arm . PVI 5-FU is a well tolerated outpatient treatment regimen for patients with CUP , although the addition of MMC provides little extra benefit . PVI 5-FU may be a potential reference regimen in r and omised trials with newer chemotherapy agents in patients with CUP Objectives : Evaluation of the safety and efficacy of docetaxel and cisplatin in the treatment of unknown primary cancer . Patients and Methods : Inclusion criteria included histologic evidence of carcinoma originating in an unknown primary organ , no prior chemotherapy , age range 20 to 75 years , WHO PS ≤3 , measurable or evaluable lesions , and adequate organ function .  Docetaxel ( 60 mg/m2 ) followed by cisplatin ( 80 mg/m2 ) was administered intravenously every 3 weeks . Patients were assessed for tumor response after 2 cycles of chemotherapy , and 4 additional cycles were administered unless disease progression was demonstrated . Results : Between September 1997 and September 2002 , 45 patients were enrolled . The median age was 56.5 years ( 28–73 years ) , and their performance status ( PS ) were 0 ( 11 patients ) , 1 ( 26 patients ) , and 2 ( 6 patients ) , respectively , ( 2 patients were removed from the trial after initial enrolment ) . A total of 26 patients ( 60 % ) presented with lymphadenopathy , 14 patients ( 33 % ) with visceral disease , and 3 ( 7 % ) with bone and soft-tissue metastases . The overall response rate was 65.1 % ( 4 complete response , 24 partial response , 8 NC , 7 progressive diseases : 95 % confidence interval , 48.0–78.4 ) . The median time to progression was 5.0 months . The median survival time was 11.8 months . No treatment-related deaths were observed . Commonly observed side effects included neutropenia ( grade 3–4 , 16 patients ) , nausea ( grade 3 , 13 patients ) , and nephrotoxicity ( grade 2 , 5 patients ) . Conclusions : These results indicate that the combination of docetaxel and cisplatin is a safe and effective regimen for patients with unknown primary cancer
Background : Although chemotherapeutic regimens containing a taxane or platinum agent have been widely recommended for unfavourable carcinoma of unknown primary ( CUP ) , no evidence exists for the superiority of any administered regimens .
To date , the efficacy has been mostly assessed in the limited setting of phase II trials , and few attempts have been made to synthesis e all available data for survival outcomes .