***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: PURPOSE To investigate the potential gain of the concomitant use of radiotherapy and chemotherapy in improving local control and reducing the need for colostomy , a r and omized phase III trial was performed in patients with locally advanced anal cancer . MATERIAL S AND METHODS From 1987 to 1994 , 110 patients were r and omized between radiotherapy alone and a combination of radiotherapy and chemotherapy .  The patients had T3 - 4NO-3 or T1 - 2N1 - 3 anal cancer .  Radiotherapy consisted of 45 Gy given in 5 weeks , with a daily dose of 1.8 Gy . After a rest period of 6 weeks , a boost of 20 or 15 Gy was given in case of partial or complete response , respectively . Surgical resection as part of the primary treatment was performed if possible in patients who had not responded 6 weeks after 45 Gy or with residual palpable disease after the completion of treatment . Chemotherapy was given during radiotherapy : 750 mg/m2 daily fluorouracil as a continuous infusion on days 1 to 5 and 29 to 33 , and a single dose of mitomycin 15 mg/m2 administered on day 1 . RESULTS The addition of chemotherapy to radiotherapy result ed in a significant increase in the complete remission rate from 54 % for radiotherapy alone to 80 % for radiotherapy and chemotherapy , and from 85 % to 96 % , respectively , if results are considered after surgical resections . This led to a significant improvement of locoregional control and colostomy-free interval ( P = .02 and P = .002 , respectively ) , both in favor of the combined modality treatment . The locoregional control rate improved by 18 % at 5 years , while the colostomy-free rate at that time increased by 32 % by the addition of chemotherapy to radiotherapy . No significant difference was found when severe side effects were considered , although anal ulcers were more frequently observed in the combined-treatment arm . The survival rate remained similar in both treatment arms . Skin ulceration , nodal involvement , and sex were the most important prognostic factors for both local control and survival . These remained significant after multivariate analysis . The improvement seen in local control by adding chemotherapy to radiotherapy also remained significant after adjusting for prognostic factors in the multivariate analysis . Event-free survival , defined as free of locoregional progression , no colostomy , and no severe side effects or death , showed significant improvement ( P = .03 ) in favor of the combined-treatment modality . The 5-year survival rate was 56 % for the whole patient group . CONCLUSION The concomitant use of radiotherapy and chemotherapy result ed in a significantly improved locoregional control rate and a reduction of the need for colostomy in patients with locally advanced anal cancer without a significant increase in late side effects Ifosfamide ( IFOS ) 5 g/m2 and its parent analog Cyclophosphamide ( CYCLO ) 1.5 g/m2 were studied in a r and omized phase II study , accruing 171 patients with advanced soft tissue sarcoma . Both drugs were administered as 24 hr infusions , every 3 weeks , with comcomitant Mesna 400 mg/m2 i.v . bolus 4 hourly X 9 doses . Twenty-four patients were ineligible and 12 were not evaluable . The groups were well matched for age , previous chemotherapy ( 42 % of the total ) or radiotherapy , the presence of distant metastases and performance status , but there were more females ( 59 % vs. 45 % ) in the IFOS arm . Among the 68 evaluable patients receiving IFOS , there were 2 CR , 10 PR ( overall response 18 % ) , 27 SD and 29 PD . For CYCLO , the corresponding results in 67 patients were 1 CR , 4 PR ( overall response 8 % ) , 23 SD and 39 PD . Using the chi-square test the P values for response rate and linear trend were 0.13 and 0.04 respectively . Response rates were higher for females ( 20 % vs. 5 % , P = 0.01 ) and patients who had not received previous chemotherapy ( 19 % vs. 4 % , P = 0.01 ) . Fourteen of the 17 responses came from a group of 43 females , who had not received previous chemotherapy , for whom the overall response rate was 37.5 % . Remissions were noted in only 4 histological subtypes ( central ly review ed material ) , i.e. , 5 of 17 synovial sarcomas , 7 of 13 mixed mesodermal sarcomas and 2 of 7 fibrosarcomas . One of the 31 leiomyosarcomas responded to Cyclophosphamide .  Duration s of response did not differ significantly between the 2 arms -- median 26 , range 10 - 81 + weeks . Leucopenia was significantly more severe on CYCLO , particularly in patients who had received previous chemotherapy ( P = 0.007 ) . Serious infections occurred in approx . 7 % of patients with no difference between the two drugs , although there was one toxic death on CYCLO .  Nausea and vomiting were significantly worse on  IFOS  and alopecia , related in extent to dose , was seen in both arms . Other side-effects , such as hematuria or rises in serum creatinine and encephalopathy , were infrequent and mild . A higher response rate with less myelosuppression suggests that IFOS may have advantages over CYCLO in combination therapy Introduction : Previous data suggest that women may live longer with advanced non-small cell lung cancer ( NSCLC ) than men . We evaluated whether sex affected survival in the Eastern Cooperative Oncology Group ( ECOG ) E1594 trial . E1594 r and omized patients with advanced NSCLC to one of four platinum doublets and found that all four regimens had comparable efficacy . Patients and Methods : Patients in the E1594 data base were divided into male and female cohorts ; response and survival were calculated separately for each cohort . Known prognostic factors and differences in toxicity profiles were compared between the two cohorts . Results : All 1157 eligible patients ( 431 women , 726 men ) from E1594 were included in this analysis . There was no statistically significant difference in performance status , weight loss of > 10 % , stage , or incidence of brain metastases between women and men . Response rates were similar ( 19 % for both ; P = 0.15 ) . The median survival time for women , however , was significantly longer at 9.2 months ( 95 % CI , 8.1–10.4 months ) versus only 7.3 months for men ( 95 % CI , 6.8–8.0 months ) ( P = 0.004 log-rank test ) . Toxicity was generally greater in women than in men . Conclusions : Women in ECOG 1594 had a 1.9-month statistically significant improvement in median survival compared with men , despite similar response rates and greater toxicity and no difference in other known prognostic factors . These data strongly support the significance of sex as a separate prognostic factor in advanced NSCLC and emphasize the importance of sex as a stratification factor in future phase III NSCLC trials UNLABELLED Currently , available chemotherapy regimens for patients with advanced or recurrent endometrial cancer are generally not curative . Thus , there is a need to identify more active single agents in this disease . In this study patients pre-treated and not pre-treated with first line combination chemotherapy  were entered into a r and omized phase II study of either cyclophosphamide ( CYCLO ) or Ifosfamide ( IFOS ) . PATIENTS AND METHOD Sixty one eligible patients with recurrent or metastatic histologically proven , adenocarcinoma of the uterine corpus entered the study . The median age at entry was 62 ( range 40 - 74 ) years . Twenty patients ( 33 % ) had prior hormonal treatment and 31 ( 51 % ) prior chemotherapy .  CYCLO was given at a dose of 1200 mg/m2 and IFOS at a dose of 5 g/m2 . Both drugs were administered i.v . over 24 hours on day one every three weeks . Adequate pre- and post hydration as well as use of Mesna in the Ifosfamide arm were m and atory . RESULTS A median of two treatment cycles ( range 1 - 12 ) per patient were given . In the chemotherapy-naive patients , in the CYCLO arm two PRs ( RR 14 % , C.I. 2 - 43 % ) were seen and in the IFOS arm two CRs , two PRs , ( RR 25 % , C.I. 7 - 52 % ) were observed . No responses were seen in pre-treated patients . The duration of responses were : 15 + , 7 + months for the CRs , 15 + and 5 months for PRs in IFOS arm and 67 + , 4 months in CYCLO arm . The hematological toxicity was dose-limiting and similar in both treatment arms . No serious non hematological toxicities were reported , but a transient increase of the creatinine blood level was seen in two IFOS patients ( 6 % ) . CONCLUSION Ifosfamide is an active drug in the treatment of chemotherapy-naive patients with advanced endometrial cancer and its application in currently used ( combination ) regimens should be considered BACKGROUND Based on the r and omised Euro-EWING99-R1 trial , vincristine , adriamycin , cyclophosphamide ( VAC ) may be able to replace vincristine , adriamycin , ifosfamide ( VAI ) in the treatment of st and ard-risk Ewing sarcoma . However some heterogeneity of treatment effect by gender was observed . The current exploratory study aim ed at investigating the influence of gender on treatment efficacy and acute toxicity . PATIENTS AND METHODS Impact of gender on event-free survival ( EFS ) , acute toxicity by course , switches between treatment arms and cumulative dose of alkylating agents was evaluated in multivariable models adjusted for age including terms to test for heterogeneity of treatment effect by gender . The analysis of the EFS was performed on the intention-to-treat population . RESULTS EFS did not significantly differ between the 509 males and 347 females ( p=0.33 ) , but an interaction in terms of efficacy was suspected between treatment and gender ( p=0.058 ) : VAC was associated with poorer EFS than VAI in males , hazard ratio ( HR ) (VAC/VAI)=1.37 [ 95 % confidence interval ( CI ) , 0.98 - 1.90 ] , contrasting with HR=0.81 [ 95%CI , 0.53 - 1.24 ] in females . Severe toxicity was more frequent in females , whatever the toxicity type . Thirty patients switched from VAI to VAC ( 9/251 males , 4 % , and 21/174 females , 12 % ) mostly due to renal toxicity , and three from VAC to VAI ( 2/258 males , 0.8 % , and 1/173 females , 0.6 % ) . A reduction of alkylating agent cumulative dose > 20 % was more frequent in females ( 15 % versus 9 % , p=0.005 ) , with no major difference between VAC and VAI ( 10 % versus 13 % , p=0.15 ) . CONCLUSION Differences of acute toxicity rate and cumulative doses of alkylating agents could not explain the marginal interaction observed in the Euro-EWING99-R1 trial data . Effects of gender-dependent polymorphism/activity of metabolic enzymes ( e.g. known for CYP2B6 ) of ifosfamide versus cyclophosphamide should be explored . External data are required to further evaluate whether there is heterogeneity of alkylating agent effect by gender . TRIAL NUMBERS NCT00987636 and EudraCT 2008 - 003658 - 13 BACKGROUND ALCL99 protocol including six courses of chemotherapy derived from the NHL-BFM protocol is widely used for the treatment of paediatric anaplastic large-cell lymphoma . In the ALCL99 trial , patients were r and omised to receive MTX 1 g/m² in 24 hr with intrathecal injection ( MTX1 ) versus MTX 3 g/m² in 3 hr without intrathecal ( MTX3 ) ; then to receive or not vinblastine ( high-risk patients ) . The present study provides information about the acute adverse reactions ( ARs ) during the six courses of the ALCL99 treatment , assesses risk factors for ARs and evaluates the risk of overweight related to treatment . METHODS Data concerning ARs were assessed using CTCv2 and analysed overall and according to the type of course . RESULTS Between 1999 and 2005 , 352 patients were recruited . Toxicity assessed after 2050 courses included grade 4 neutropaenia ( 70 % of courses ) , grade 3 - 4 stomatitis ( 13 % ) , grade 3 - 4 transaminase elevation ( 10 % ) and grade 3 - 4 infection ( 5 % ) . Four patients ( 1 % ) died of toxicity . The toxicity profile differed between courses-A ( significantly more haematological toxicity ) and courses-B ( significantly more stomatitis ) . The percentage of ARs was higher after the first course than after subsequent courses . Severe toxicity was more frequent after MTX1 than after MTX3 courses but did not differ between courses with or without vinblast 
    Output:
    
Our meta- analysis did not confirm the hypothesis of a treatment-by-sex interaction on efficacy or toxicity outcomes