***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    Input: BACKGROUND Economic information is necessary for rational decision-making in health care . Many European countries require financial impact statements prior to drug approval , and many health care organizations in the USA consider cost-effectiveness when making formulary decisions . We report the findings and discuss the policy implication s of an economic evaluation based on an international , r and omized controlled trial of salvage therapy for epithelial ovarian cancer , wherein topotecan and pegylated liposomal doxorubicin ( PLD ) were found to have similar efficacy but differing toxicities . PATIENTS AND METHODS Direct costs to the payer were estimated for 235 North American and 239 European trial participants who had relapsed or failed platinum-based therapy .  Unit costs were obtained from national sources or previously reported economic analyses . Sensitivity analyses were also performed . RESULTS Total cost per person in the topotecan arm was 12,325 dollars ( 95 % CI 9445 dollars to 15,415 dollars ; P > 0.05 ) higher in the USA-based analysis and 2909 dollars ( 95 % CI 779 dollars to 3415 dollars ; P < 0.05 ) higher in the UK-based analysis than for PLD . Pegylated liposomal doxorubicin was cost saving over a wide range of assumptions . The main differences ( per person ) in toxicity management following PLD compared with topotecan in Europe were for blood transfusions ( 1190 dollars versus 181 dollars , respectively ) and hospitalizations ( 1197 dollars versus 280 dollars , respectively ) . In North America , differences were mainly for granulocyte colony stimulating factors ( 1936 dollars versus 419 dollars micro g , respectively ) , erythropoietin ( 3493 dollars versus 308 dollars , respectively ) and blood transfusions ( 1346 dollars versus 140 dollars , respectively ) . CONCLUSIONS Policy makers who evaluate pharmacoeconomic studies should consider international differences in health care delivery . Cost assessment s based on information obtained from one country may not be relevant for policy makers in a different country INTRODUCTION Topotecan inhibits the topoisomerase-I enzyme result ing its stabilisation on the DNA and the suspension of replication and transcription . AIMS The authors summarized their first experience on second-line topotecan treatment in a prospect i ve non-r and omized study . METHOD Topotecan was given for recurrent epithelial ovarian cancer in the dose of 1.5 mg/m2/d for 5 days repeated in every 3 weeks in a 30-minute infusion intravenously . RESULTS Twenty five recurrent ovarian cancer patients were treated between March , 1999 and March , 2001 .  Complete and partial response rates were found 12 % and 12 % , respectively . Stable disease was observed in 48 % of patients for 4 - 8 courses , then progression continued . In these 3 groups of patients the median progression free interval was shown as 12 weeks . CONCLUSION When comparing to previous chemotherapies , topotecan treatment failed to show a definitive improvement in the outcome of recurrent ovarian cancer The dose-limiting toxicities of the DNA topoisomerase I inhibitor topotecan are hematological . We prospect ively analyzed the platelet toxicity pattern in patients receiving topotecan  to optimize the clinical management of topotecan hematotoxicity .  Twenty-one advanced ovarian cancer patients , all pretreated with cisplatin and paclitaxel  , were treated with 1.25 mg/m2/day topotecan as a 30 min infusion for 5 days , every 3 weeks . No prophylactic granulocyte colony stimulating factor ( G-CSF ) was given . No topotecan dose reduction was planned according to hematologic toxicity . One hundred and thirty-three topotecan courses were administered ( median per patient 6 ; range : 1 - 15 ) . Despite no dose reduction , the mean platelet nadir values were significantly less pronounced at cycle 2 than at cycle 1 ( 82 versus 46 x 10(3)/mm3 , p=0.0007 ) . Similar differences were found between cycle 1 and any following cycle . The percent of patients experiencing grade 4 thrombocytopenia decreased from 43 % at the first cycle , to 15 and 19 % at the second and third courses , respectively ( p=0.058 ) . We conclude that the currently recommended topotecan schedule is feasible in heavily pretreated ovarian cancer patients without prophylactic G-CSF . The severity of topotecan-induced  thrombocytopenia is maximal at the first cycle but significantly decreases from the second cycle in the absence of dose reduction PURPOSE To evaluate oral topotecan as single-agent , second-line therapy in patients with ovarian cancer previously treated with a platinum-based regimen . PATIENTS AND METHODS Patients ( N = 116 ) received oral topotecan 2.3 mg/m2 daily for 5 days every 21 days . Eligibility criteria included histologic diagnosis of International Federation of Gynecology and Obstetrics stage III or IV epithelial ovarian cancer , bidimensionally measurable disease , prior platinum-containing chemotherapy , age > or = 18 years , performance status < or = 2 , and life expectancy > or = 12 weeks . RESULTS Overall response rate was 21.6 % ( 25 of 116 patients ) . Median duration of response was 25.0 weeks ; median time to response was 8.4 weeks . Median time to progression was 14.1 weeks ; median survival was 62.2 weeks . Grade 4 neutropenia was experienced by 50.4 % of patients in 13.4 % of courses administered . Grade 4 thrombocytopenia was experienced by 22.1 % of patients in 5.1 % of courses . Grade 3 or 4 anemia was experienced by 29.2 % of patients in 8.5 % of courses . Most frequent nonhematologic toxicities were predominantly ( > 90 % ) grade 1 or 2 and included nausea , alopecia , diarrhea , and vomiting . CONCLUSION Second-line oral topotecan administered at 2.3 mg/m2 for 5 days every 21 days demonstrated activity in patients with progressive or recurrent ovarian cancer after first-line platinum-based chemotherapy . This activity was comparable to that seen in previous studies with intravenous topotecan . Grade 4 neutropenia was less frequent with oral topotecan than previously reported for intravenous topotecan . Oral topotecan is an active , tolerable , and convenient formulation of an established agent for the second-line treatment of advanced epithelial ovarian cancer and may also facilitate exploring prolonged treatment schedules BACKGROUND We have continued to monitor the survival of patients r and omised in a previously reported multicentre phase III study of topotecan versus paclitaxel in patients with advanced epithelial ovarian cancer who had failed one prior platinum-based regimen . PATIENTS AND METHODS Patients with bidimensionally measurable disease were r and omised to topotecan  ( 1.5 mg/m(2)/day for 5 days ) or paclitaxel ( 175 mg/m(2)/day as a 3-h infusion ) every 21 days . Patients were eligible for treatment with the alternate therapy at third line . The European Organisation for Research and Treatment of Cancer Quality of Life ( EORTC QOL)-C30 question naire was also used to measure eight symptoms at baseline and during each course ( pain , anorexia , diarrhoea , fatigue , nausea and vomiting , dyspnea , constipation and insomnia ) . RESULTS A total of 226 patients were evaluable for response . Demographic characteristics were similar in both treatment groups , as were results of the EORTC QOL-30 question naire . For the topotecan group , median time to progression was 18.9 weeks ( range < 1 to 92.6 + weeks ; 25 % censored ) , and , for paclitaxel , 14.7 weeks ( range < 1 to 137.3 + weeks ; 12.3 % censored ) ; P = 0.076 . At 4 years post-r and omisation , median survival in the topotecan group was 63.0 weeks ( range < 1 to 238.4 + weeks ; 20.5 % censored ) and , for paclitaxel , 53.0 weeks ( range < 1 to 226.3 + weeks ; 12.3 % censored ) ; P = 0.44 . CONCLUSION Topotecan continues to demonstrate comparable efficacy and survival to paclitaxel with manageable and non-cumulative haematological toxicity . Non-haematological toxicity was generally mild for both groups . The long-term survival rate indicates substantial therapeutic benefit for this group of patients receiving topotecan at relapse of ovarian cancer Topotecan , administeredintravenously at a dose of 1.5 mg/m2 per day for 5 days every 21 days , is an established regimen in the treatment of recurrent ovarian carcinoma . Alternate dosing strategies have sought to improve toxicity . The authors evaluated the tolerability and antitumor activity of a 3‐day topotecan regimen A phase II programme was carried out in both Europe and North America to evaluate the activity of topotecan administered as a 21-day continuous intravenous infusion to patients with recurrent ovarian cancer . The European results are reported here . Patients who had failed first line therapy with a platinum-based regimen received topotecan 0.4 mg/m2/day , as a 21-day infusion every 28 days . Patients were only permitted one prior regimen . 35 patients were enrolled and evaluable for response . 3 patients ( 8.6 % ) had a partial response to treatment ( 95 % CI 1.8 % , 23.1 % ) with a median time to response of 8.1 weeks and a median duration of response of 17.6 weeks . Response was also evaluated by CA125 and was also found to be 8 % . For all 35 patients , median time to progression was 16.1 weeks and median survival was 43.6 weeks . The principal toxicity was myelosuppression although grade 4 neutropenia occurred in only 8.8 % of patients ( 2.1 % of courses ) and infectious complications were relatively infrequent . Non-haematological toxicity was generally mild and mainly consisted of gastrointestinal events , alopecia and fatigue . A prolonged infusion of topotecan was well tolerated with a low incidence of severe neutropenia . Responses were seen in both North American and European patients . Response rates varied between the 2 studies possibly due to differences in patient demographics . © 2001 Cancer Research PURPOSE As topotecan is S-phase-specific , its efficacy is likely schedule-dependent . Therefore , a r and omized study using a " pick the winner " design was undertaken to compare two schedules in patients with recurrent ovarian cancer . PATIENTS AND METHODS Patients with recurrent epithelial ovarian cancer previously treated with no more than two separate regimens of chemotherapy , one of which had to be platinum-containing  , were  r and omized  to either topotecan 1.5 mg/m2 intravenously ( i.v . ) over 30 minutes daily for 5 days repeated every 21 days ( arm A , the st and ard arm ) , or topotecan 1.75 mg/m2 as a 24-hour infusion once a week for 4 weeks repeated every 6 weeks ( arm B , the experimental arm ) . RESULTS Sixty-six patients were eligible and 63 were assessable for response . The response rate in arm A was 22.6 % ( 95 % confidence interval [ CI ] , 9.6 % to 41.2 % ) , which was significantly superior to that in arm B , 3.1 % ( 95 % CI , 0.1 % to 16 % ) ( P = .026 ) . The regimens were not equitoxic , with 94 % of patients on arm A experiencing grade 3 or 4 granulocytopenia as opposed to 52 % on arm B. CONCLUSION The weekly 24 hour infusion of topotecan at 1.75 mg/m2 was ineffective in relapsed ovarian cancer . The daily-times-five schedule remains the schedule of choice . As the regimens were not equitoxic , one can not differentiate between an ineffective schedule and an ineffective dose as the reason for the differing response rates . However , the degree of myelotoxicity that already occurs will preclude any substantially higher dosing with the weekly regimen The objectives of this study were to investigate the tolerability of a novel high-dose chemotherapy ( HDC ) regimen with peripheral blood progenitor cell ( PBPC ) support in patients with pretreated advanced ovarian cancer and to determine the maximum-tolerated dose ( MTD ) of topotecan in this setting . Advanced ovarian cancer patients previously treated with platinum-based first-line therapy were enrolled . After PBPC mobilization and harvesting , patients received three consecutive cycles of HDC with PBPC support . Cycle 1 was carboplatin area under the concentration curve 20 and paclitaxel 250 mg/m2 . Cycle 2 was topotecan starting at 5 mg/m2 , dose escalated in 2 mg/m2 increments , and etoposide 600 mg/m2 . Cycle 3 was 
    Output:
    
Small tumor diameter , sensitivity to platinum-based chemotherapy was associated with better prognosis .
Topotecan appears to have a similar level of effectiveness as paclitaxel and PLD , though with different patterns of side effects .