***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: OBJECTIVE Carboplatin-based combinations are commonly used in platinum-sensitive ovarian cancer ( PSOC ) .  Pemetrexed in combination with carboplatin has been shown to be feasible in a phase I study in PSOC . The primary objective of this subsequent phase II study was to determine the overall response rate ( ORR ; defined by Response Evaluation Criteria in Solid Tumors ) of this combination in patients with recurrent PSOC . Secondary objectives included progression-free survival ( PFS ) , overall survival ( OS ) , and toxicity . METHODS Patients with PSOC ( defined by recurrence ≥ 6 months after completion of up to two lines of prior platinum-based therapy ) , measurable disease , Eastern Cooperative Oncology Group performance status of 0 to 2 , and adequate organ function were eligible .  Pemetrexed 500 mg/m(2 ) was administered as a 10-minute infusion followed by carboplatin AUC 6 as a 30-minute infusion on day 1 of a 21-day cycle . RESULTS Sixty-six patients were treated . Of the 61 patients evaluable for response , there were 20 responders ( one complete response and 19 partial responses ) , for an ORR of 32.8 % ( 95 % CI : 21.3 % , 46.0 % ) . For the intent-to-treat population ( all 66 patients ) , the median PFS was 9.4 months ( 95 % CI : 8.3 , 11.1 ) , with 22.7 % censoring . Median OS was not reached due to the high censoring rate . There was one drug-related death ( multi-organ failure ) . The most common drug-related grade 3/4 toxicities were neutropenia ( 39.4 % ) , thrombocytopenia ( 24.2 % ) , carboplatin hypersensitivity ( 9.1 % ) , nausea ( 6.1 % ) , and vomiting ( 6.1 % ) . CONCLUSIONS Carboplatin AUC 6 and pemetrexed 500 mg/m(2 ) has a low incidence of serious toxicities . Defining the platinum-based combination with the best therapeutic index would require a prospect i ve phase III study OBJECTIVE We aim ed to evaluate the efficacy and safety of combination bevacizumab/pemetrexed for the treatment of recurrent epithelial ovarian cancer ( EOC ) . METHODS Platinum-sensitive or -resistant patients with recurrent or persistent EOC were eligible if they had received up to 2 prior chemotherapy regimens , including a platinum/taxane regimen without prior bevacizumab . Pemetrexed 500 mg/m(2 ) IV and bevacizumab 15 mg/kg IV were administered every 3 weeks . The primary endpoint was 6-month progression-free survival ( PFS ) ; other endpoints included toxicities , PFS and overall survival ( OS ) . RESULTS Thirty-four patients received a median of 7 treatment cycles ( range , 2 - 26 ) . Median follow-up was 25.7 months ( range , 3.0 - 47.2 ) . Six month progression-free survival ( PFS ) was 56 % ( 95 % CI : 38 - 71 ) . The following response rates were documented ( % ; 95 % CI ) : 0 complete response , 14 partial responses ( 41 % ; 25 - 59 ) , 18 stable disease ( 53 % ; 35 - 70 ) and 2 progressive disease ( 6 % ; 1 - 20 ) . Median PFS was 7.9 months ( 95 % CI , 4.6 - 10.9 ) , with a median OS of 25.7 months ( 95 % CI , 15.4 - 29.8 ) . Twenty-two patients ( 64.7 % ) had a platinum-free interval ( PFI ) of > 6 months prior to enrollment . Grade 3 - 4 hematologic toxicities included neutropenia ( 50 % ) , leukopenia ( 26 % ) , thrombocytopenia ( 12 % ) and anemia ( 9 % ) . Non-hematologic grade 3 - 4 toxicities included metabolic ( 29 % ) , constitutional ( 18 % ) , pain ( 18 % ) and gastrointestinal ( 15 % ) . Two patients developed hematologic malignancies within one year of treatment . CONCLUSIONS Combination bevacizumab/pemetrexed is an active option for both platinum-sensitive and -resistant recurrent EOC . Further investigation of cost and novel toxicities associated with this regimen may be warranted BACKGROUND This phase I and pharmacokinetic study of pemetrexed in combination with oxaliplatin was performed to determine the maximum tolerated dose ( MTD ) , and to evaluate safety and pharmacokinetics in patients with metastatic solid tumors . PATIENTS AND METHODS Pemetrexed was administered as a 10- min i.v . infusion followed 30 min later by oxaliplatin as a 2- h infusion , once every 21 days . Up to two previous chemotherapy regimens were allowed . Vitamin B(12 ) supplementation and folic acid were not included in this study . RESULTS Thirty-six patients were treated in six escalating dose levels . Dose-limiting toxicities at dose level 6 ( pemetrexed 500 mg/m(2 ) plus oxaliplatin 130 mg/m(2 ) ) were febrile neutropenia , grade 3 - 4 diarrhea and grade 3 paresthesia . The MTD was not reached . The most common toxicity was neutropenia , with grade 3 - 4 occurring in 61 % of patients . The pharmacokinetics of this pemetrexed-oxaliplatin combination are consistent with those following single-agent administration . Five responses ( all partial ) were observed over a broad range of solid tumors . CONCLUSIONS This pemetrexed-oxaliplatin combination ( without vitamin supplementation ) every 21 days can be administered using full therapeutic doses of each agent with acceptable tolerability and no overlapping toxicity . The recommended regimen for phase II studies is pemetrexed 500 mg/m(2 ) plus oxaliplatin 120 mg/m(2 ) Disease Control Rate ( DCR ) and Clinical Benefit Rate ( CBR ) are defined as the percentage of patients with advanced or metastatic cancer who have achieved complete response , partial response and stable disease to a therapeutic intervention in clinical trials of anticancer agents .  DCR and CBR are commonly reported in many clinical trials in abstract s , papers , meeting presentations and media releases . The frequent use of these measures of drug activity presents the question of whether DCR and CBR are useful additional endpoints in early clinical trials , and if they can reasonably predict the success of an agent in subsequent , adequately powered , r and omized trials . There are no comprehensive analyses to demonstrate that CBR and DCR add to the value of traditional response/activity endpoints in early clinical trials . Data from phase II clinical trials in which the DCR or CBR are reported suggest that DCR or CBR provides ambiguous information that likely exaggerates the anticancer activity of the therapy . The terms ' disease control ' and ' clinical benefit ' in the context of non-r and omized trials are themselves disingenuous because neither tumor regression nor stable disease , defined without any consideration of duration of effect or reduction of symptoms appropriate for the specific patient population , are evidence of these endpoints in an individual patient PURPOSE Patients with malignant pleural mesothelioma , a rapidly progressing malignancy with a median survival time of 6 to 9 months , have previously responded poorly to chemotherapy . We conducted a phase III trial to determine whether treatment with pemetrexed and cisplatin results in survival time superior to that achieved with cisplatin alone . PATIENTS AND METHODS Chemotherapy-naive patients who were not eligible for curative surgery were r and omly assigned to receive pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1 , or cisplatin 75 mg/m2 on day 1 . Both regimens were given intravenously every 21 days . RESULTS A total of 456 patients were assigned : 226 received pemetrexed and cisplatin , 222 received cisplatin alone , and eight never received therapy .  Median survival time in the pemetrexed/cisplatin arm was 12.1 months versus 9.3 months in the control arm ( P = .020 , two-sided log-rank test ) . The hazard ratio for death of patients in the pemetrexed/cisplatin arm versus those in the control arm was 0.77 . Median time to progression was significantly longer in the pemetrexed/cisplatin arm : 5.7 months versus 3.9 months ( P = .001 ) . Response rates were 41.3 % in the pemetrexed/cisplatin arm versus 16.7 % in the control arm ( P < .0001 ) . After 117 patients had enrolled , folic acid and vitamin B12 were added to reduce toxicity , result ing in a significant reduction in toxicities in the pemetrexed/cisplatin arm . CONCLUSION Treatment with pemetrexed plus cisplatin and vitamin supplementation result ed in superior survival time , time to progression , and response rates compared with treatment with cisplatin alone in patients with malignant pleural mesothelioma . Addition of folic acid and vitamin B12 significantly reduced toxicity without adversely affecting survival time Purpose : This phase I trial evaluated intraperitoneal ( i.p . ) pemetrexed , cisplatin , and paclitaxel in optimally debulked ovarian cancer . Experimental Design : Dose escalation of day 1 i.p . pemetrexed accrued three patients to each of five dose levels ( 60–1,000 mg/m2 ) , along with day 2 i.p . cisplatin ( 75 mg/m2 ) and day 8 i.p . paclitaxel ( 60 mg/m2 ) . The goals were to determine maximum tolerated dose ( MTD ) , 18-month progression-free survival ( PFS ) , and pharmacokinetics of i.p . pemetrexed . Results : Cycles , given every 21 days , had an 80 % 6-cycle completion rate . There was minimal grade III toxicity in the first 4 dose levels and remarkably an almost complete absence of peripheral neuropathy and alopecia . At the highest dose level , two of three patients experienced ≥ grade III and dose-limiting toxicity ( DLT ; hematologic , infection , gastrointestinal ) . There was a pharmacokinetic advantage for i.p . pemetrexed with an intraperitoneal : plasma area under the concentration – time curve ratio of 13-fold . Neither analysis of pharmacokinetic nor homocysteine levels explains the unexpected severity of toxicity in those two patients . On the basis of plasma C24h levels , the 42 cycles at ≥500 mg/m2 i.p . pemetrexed without DLT , the MTD appears to be 500 mg/m2 . Median PFS is 30.1 months ; 18-month PFS is 78.6 % ( median follow-up 22.4 months ) . Conclusions : This i.p.-only regimen in front-line ovarian cancer is feasible with PFS in line with recent literature . We suggest phase II trials of this regimen in this population with i.p . pemetrexed at 500 mg/m2 . The favorable toxicity profile at doses < 1,000 mg/m2 , which needs to be confirmed , appears to compare well with st and ard combination i.v./i.p . platinum/taxane chemotherapy in this disease . Clin Cancer Res ; 18(9 ) ; 2668–78 . © 2012 AACR Background Carboplatin-based combinations are established in platinum-sensitive recurrent ovarian cancer . To improve the therapeutic index , new platinum-based combinations are required . Pemetrexed is a multi-targeted antifolate inhibiting thymidylate synthase . The aim of this study was to determine the maximally tolerated dose ( MTD ) and dose-limiting toxicity ( DLT ) and to characterize toxicities of the combination of pemetrexed ( Pem ) and carboplatin ( Cb ) . Design A st and ard three-patient cohort dose escalation was performed starting at Cb AUC-5 and Pem 500 mg/m2 . Patients with platinum-sensitive recurrent ovarian cancer were eligible . Two levels of Cb ( AUC-5 , 6 ) and five levels of Pem ( 500 , 600 , 700 , 800 , and 900 mg/m2 ) were evaluated . DLTs were based on cycle 1 . Results Twenty patients were enrolled . The median age was 57.4 years ( 37.3–75.3 ) and the median platinum-free interval was 26.2 months ( 7.2–124.4 ) . There was one DLT at dose level 3 in cycle one . No serious adverse events related to the study therapy were observed . The 20 patients completed 112 cycles of Cb ( 104 were planned ) and 
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Again , pemetrexed was relatively well tolerated .