***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: BACKGROUND Current estimates of the costs of cancer care in the United States are based on data from 2003 and earlier . However , incidence , survival , and practice patterns have been changing for the majority of cancers . METHODS Cancer prevalence was estimated and projected by phase of care ( initial year following diagnosis , continuing , and last year of life ) and tumor site for 13 cancers in men and 16 cancers in women through 2020 . Cancer prevalence was calculated from cancer incidence and survival models estimated from Surveillance , Epidemiology , and End Results ( SEER ) Program data . Annualized net costs were estimated from recent SEER-Medicare linkage data , which included cl aims through 2006 among beneficiaries aged 65 years and older with a cancer diagnosis . Control subjects without cancer were identified from a 5 % r and om sample of all Medicare beneficiaries residing in the SEER areas to adjust for expenditures not related to cancer . All cost estimates were adjusted to 2010 dollars . Different scenarios for assumptions about future trends in incidence , survival , and cost were assessed with sensitivity analysis . RESULTS Assuming constant incidence , survival , and cost , we projected 13.8 and 18.1 million cancer survivors in 2010 and 2020 , respectively , with associated costs of cancer care of 124.57 and 157.77 billion 2010 US dollars . This 27 % increase in medical costs reflects US population changes only . The largest increases were in the continuing phase of care for prostate cancer ( 42 % ) and female breast cancer ( 32 % ) . Projections of current trends in incidence ( declining ) and survival ( increasing ) had small effects on 2020 estimates . However , if costs of care increase annually by 2 % in the initial and last year of life phases of care , the total cost in 2020 is projected to be $ 173 billion , which represents a 39 % increase from 2010 . CONCLUSIONS The national cost of cancer care is substantial and expected to increase because of population changes alone . Our findings have implication s for policy makers in planning and allocation of re sources Summary Background Therapeutic antibodies targeting EGFR have activity in advanced colorectal cancer , but results from clinical trials are inconsistent and the population in which most benefit is derived is uncertain . Our aim was to assess the addition of panitumumab to irinotecan in pretreated advanced colorectal cancer . Methods In this open-label , r and omised trial , we enrolled patients who had advanced colorectal cancer progressing after fluoropyrimidine treatment with or without oxaliplatin from 60 centres in the UK . From December , 2006 until June , 2008 , molecularly unselected patients were recruited to a three-arm design including irinotecan ( control ) , irinotecan plus ciclosporin , and irinotecan plus panitumumab ( IrPan ) groups . From June 10 , 2008 , in response to new data , the trial was amended to a prospect ively stratified design , restricting panitumumab r and omisation to patients with KRAS wild-type tumours ; the results of the comparison between the irinotcan and IrPan groups are reported here . We used a computer-generated r and omisation sequence ( stratified by previous EGFR targeted therapy and then minimised by centre , WHO performance status , previous oxaliplatin , previous bevacizumab , previous dose modifications , and best previous response ) to r and omly allocate patients to either irinotecan or IrPan . Patients in both groups received 350 mg/m2 intravenous irinotecan every 3 weeks ( 300 mg/m2 if aged ≥70 years or a performance status of 2 ) ; patients in the IrPan group also received intravenous panitumumab 9 mg/kg every 3 weeks . The primary endpoint was overall survival in KRAS wild-type patients who had not received previous EGFR targeted therapy , analysed by intention to treat . Tumour DNA was pyrosequenced for KRASc.146 , BRAF , NRAS , and PIK3CA mutations , and predefined molecular subgroups were analysed for interaction with the effect of panitumumab . This study is registered , number IS RCT N93248876 . Results Between Dec 4 , 2006 , and Aug 31 , 2010 , 1198 patients were enrolled , of whom 460 were included in the primary population of patients with KRASc.12–13,61 wild-type tumours and no previous EGFR targeted therapy . 230 patients were r and omly allocated to irinotecan and 230 to IrPan . There was no difference in overall survival between groups ( HR 1·01 , 95 % CI 0·83–1·23 ; p=0·91 ) , but individuals in the IrPan group had longer progression-free survival ( 0·78 , 0·64–0·95 ; p=0·015 ) and a greater number of responses ( 79 [ 34 % ] patients vs 27 [ 12 % ] ; p<0·0001 ) than did individuals in the irinotecan group . Grade 3 or worse diarrhoea ( 64 [ 29 % ] of 219 patients vs 39 [ 18 % ] of 218 patients ) , skin toxicity ( 41 [ 19 % ] vs none ) , lethargy ( 45 [21]% vs 24 [ 11 % ] ) , infection ( 42 [ 19 % ] vs 22 [ 10 % ] ) and haematological toxicity ( 48 [ 22 % ] vs 27 [ 12 % ] ) were reported more commonly in the IrPan group than in the irinotecan group . We recorded five treatment-related deaths , two in the IrPan group and three in the irinotecan group . Interpretation Adding panitumumab to irinotecan did not improve the overall survival of patients with wild-type KRAS tumours . Further refinement of molecular selection is needed for substantial benefits to be derived from EGFR targeting agents . Funding Cancer Research UK , Amgen PURPOSE We performed this phase III study to compare the irinotecan , leucovorin ( LV ) , and fluorouracil ( FU ) regimen ( FOLFIRI ) versus the oxaliplatin , LV , and FU regimen ( FOLFOX4 ) in previously untreated patients with advanced colorectal cancer . PATIENTS AND METHODS A total of 360 chemotherapy-naive patients were r and omly assigned to receive , every 2 weeks , either arm A ( FOLFIRI : irinotecan 180 mg/m(2 ) on day 1 with LV 100 mg/m(2 ) administered as a 2-hour infusion before FU 400 mg/m(2 ) administered as an intravenous bolus injection , and FU 600 mg/m(2 ) as a 22-hour infusion immediately after FU bolus injection on days 1 and 2 [ LV5FU2 ] ) or arm B ( FOLFOX4 : oxaliplatin 85 mg/m(2 ) on day 1 with LV5FU2 regimen ) . RESULTS One hundred sixty-four and 172 patients were assessable in arm A and B , respectively . Overall response rates ( ORR ) were 31 % in arm A ( 95 % CI , 24.6 % to 38.3 % ) and 34 % in arm B ( 95 % CI , 27.2 % to 41.5 % ; P = .60 ) . In both arms A and B , median time to progression ( TTP ; 7 v 7 months , respectively ) , duration of response ( 9 v 10 months , respectively ) , and overall survival ( OS ; 14 v 15 months , respectively ) were similar , without any statistically significant difference . Toxicity was mild in both groups : alopecia and gastrointestinal disturbances were the most common toxicities in arm A ; thrombocytopenia and neurosensorial were the most common toxicities in arm B. Grade 3 to 4 toxicities were uncommon in both arms , and no statistical significant difference was observed . CONCLUSION There is no difference in ORR , TTP , and OS for patients treated with the FOLFIRI or FOLFOX4 regimen . Both therapies seemed effective as first-line treatment in these patients . The difference between these two combination therapies is mainly in the toxicity profile This study compared the costs and effects of insecticide (permethrin)-treated bed net ( ITN ) use in children less than five years of age in an area of intense , perennial malaria transmission in western Kenya . The data were derived from a group-r and omized controlled trial of ITNs conducted between 1996 and 1999 . The annual net cost per life-year gained was 34 U.S. dollars and the net annual cost per all-cause sick child clinic visit averted was 49 U.S. dollars . After taking into account a community effect ( protection from malaria afforded to non-ITN users who lived within 300 meters from users ) these estimates decreased to 25 U.S. dollars and 38 U.S. dollars , respectively . This study provides further evidence that ITNs are a highly cost-effective use of scarce health care re sources BACKGROUND To compare the efficacy and safety of pharmacokinetically ( PK ) guided fluorouracil ( 5-FU ) dose adjustment vs. st and ard body-surface-area ( BSA ) dosing in a FOLFOX ( folinic acid , fluorouracil , oxaliplatin ) regimen in metastatic colorectal cancer ( mCRC ) . PATIENTS AND METHODS A total of 118 patients with mCRC were administered individually determined PK-adjusted 5-FU in first-line FOLFOX chemotherapy . The comparison arm consisted of 39 patients , and these patients were also treated with FOLFOX with 5-FU by BSA . For the PK-adjusted arm 5-FU was monitored during infusion , and the dose for the next cycle was based on a dose-adjustment chart to achieve a therapeutic area under curve range ( 5-FU(ODPM Protocol ) ) . RESULTS The objective response rate was 69.7 % in the PK-adjusted arm , and median overall survival and median progression-free survival were 28 and 16 months , respectively . In the traditional patients who received BSA dosage , objective response rate was 46 % , and overall survival and progression-free survival were 22 and 10 months , respectively . Grade 3/4 toxicity was 1.7 % for diarrhea , 0.8 % for mucositis , and 18 % for neutropenia in the dose-monitored group ; they were 12 % , 15 % , and 25 % , respectively , in the BSA group . CONCLUSIONS Efficacy and tolerability of PK-adjusted FOLFOX dosing was much higher than traditional BSA dosing in agreement with previous reports for 5-FU monotherapy PK-adjusted dosing . Analysis of these results suggests that PK-guided 5-FU therapy offers added value to combination therapy for mCRC PURPOSE Severe toxicity is commonly observed in cancer patients receiving irinotecan . UDP-glucuronosyltransferase 1A1 ( UGT1A1 ) catalyzes the glucuronidation of the active metabolite SN-38 . This study prospect ively evaluated the association between the prevalence of severe toxicity and UGT1A1 genetic variation . PATIENTS AND METHODS Sixty-six cancer patients with advanced disease refractory to other treatments received irinotecan 350 mg/m(2 ) every 3 weeks . Toxicity and pharmacokinetic data were measured during cycle 1 . UGT1A1 variants ( -3279G > T , -3156G > A , promoter TA indel , 211G > A , 686C > A ) were genotyped . RESULTS The prevalence of grade 4 neutropenia was 9.5 % . Grade 4 neutropenia was much more common in patients with the TA indel 7/7 genotype ( 3 of 6 patients ; 50 % ) compared with 6/7 ( 3 of 24 patients ; 12.5 % ) and 6/6 ( 0 of 29 patients ; 0 % ) ( P = .001 ) . The TA indel genotype was significantly associated with the absolute neutrophil count nadir ( 7/7 < 6/7 < 6/6 , P = .02 ) . The relative risk of grade 4 neutropenia was 9.3 ( 95 % CI , 2.4 to 36.4 ) for the 7/7 patients versus the rest of the patients . Pretreatment total bilirubin levels ( mean + /- st and ard deviation ) were significantly higher in patients with grade 4 neutropenia ( 0.83 + /- 0.08 mg/dL ) compared to those without grade 4 neutropenia ( 0.47 + /- 0.03 mg/dL ; P < .001 ) . The -3156G > A variant seemed to distinguish different phenotypes of total bilirubin within the TA indel genotypes . The -3156 genotype and the SN-38 area under the concentration versus time curve were significant predictors of ln(absolute neutrophil count nadir ; r(2 ) = 0.51 ) . CONCLUSION UGT1A1 genotype and total bilirubin levels are strongly associated with severe neutropenia , and could 
    Output:
    
Older agents such as 5-fluorouracil , irinotecan , and oxaliplatin provide high-value treatments .
More modern agents targeting the EGFR or VEGF pathways , such as bevacizumab , cetuximab , and panitumumab , do not appear to be cost-effective treatments at their current costs .
Drugs recently approved by the US Food and Drug Administration for mCRC are not cost-effective , and this is primarily driven by high drug costs