***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 Targeting the vascular endothelial growth factor or the epidermal growth factor receptor ( EGFR ) has shown efficacy in advanced colorectal cancer ( ACC ) , but no data are available on the combination of these strategies with chemotherapy in the first-line treatment . The CAIRO2 study evaluates the effect of adding cetuximab , a chimeric mAb against EGFR , to capecitabine , oxaliplatin and bevacizumab in the first-line treatment of ACC . PATIENTS AND METHODS In all , 755 patients were r and omly assigned between treatment with capecitabine , oxaliplatin and bevacizumab with or without cetuximab . The primary end point is progression-free survival . We here present the toxicity results in the first 400 patients that entered the study . RESULTS The incidence of overall grade 3 - 4 toxicity was significantly higher in arm B compared with arm A ( 81 % versus 72 % , P = 0.03 ) . This difference is fully attributed to cetuximab-related skin toxicity . The addition of cetuximab did not result in an increase of gastrointestinal toxicity or treatment-related mortality . CONCLUSIONS The addition of cetuximab to capecitabine , oxaliplatin and bevacizumab in the first-line treatment of ACC appears to be safe and feasible . No excessive or unexpected toxicity in the cetuximab-containing treatment arm was observed Patients treated with platinum compounds are subject to hypersensitivity reactions . Our study has highlighted the reactions related to oxaliplatin ( OHP ) infusion . One hundred and twenty-four patients affected by advanced colorectal cancer were treated with different schedules containing OHP , at the Institute of Haematology and Medical Oncology ‘ L. and A. Seragnoli ’ of Bologna and at the Medical Oncology Division of Livorno Hospital . Seventeen patients ( 13 % ) showed hypersensitivity reactions after a few minutes from the start of the OHP infusion . Usually , these reactions were seen after 2–17 exposures to OHP ( Mean±s.e . : 9.4±1.07 ) . No patient experienced allergic reactions at his/her first OHP infusion . Eight patients developed a mild reaction consisting of flushing and swelling of the face and h and s , itching , sweating and lachrymation . The remaining nine patients showed a moderate – severe reaction with dyspnoea , wheezing , laryngospasm , psycho-motor agitation , tachycardia , precordial pain , diffuse erythema , itching and sweating . Six patients out of 17 were re-exposed to the drug with premedication of steroids and all except one developed the hypersensitivity reaction again . The cumulative dose , the time of exposure to OHP and the clinical features are variable and unpredictable . The risk of developing hypersensitivity reactions in patients treated with a short infusion of OHP can not be underestimated INTRODUCTION The aim of this study was to evaluate the efficacy and tolerance of cetuximab ( Cx ) in patients with irinotecan-refractory metastatic colorectal cancer ( IRMCRC ) treated routinely at five university hospitals . PATIENTS AND METHODS Data from all patients treated with Cx ( N=105 ) during the study period ( between January 2004 and September 2005 ) were included in the analysis . RESULTS Median number of  Cx  infusions was 12 ( range : 1 to 62 ) . Objective response rate was 24.8 % ; stable disease in 23.8 % ; progression in 34.3 % ; 17.1 % of the patients were not evaluable . Digestive and hematological adverse events were grade III in 20 % and 12 % , respectively , and grade IV in 12 % and 11 % , respectively . Response rates were higher in patients with acne-like rashes than in patients without ( P=0.005 ) . Median time to tumor progression ( TTP ; intention-to-treat ) was 3.9 months ( 95 % CI : 2.6 - 4.8 ) . Median overall survival after Cx initiation was 8.3 months ( 95 % CI : 6.310.7 ) . Four prognostic factors were significantly associated with a shorter TTP : center ( Center 4 : HR=2.25 , 95 % CI : 1.16 - 4.35 , P=0.017 ) ; absence of hepatic metastases ( HR=2.5 , 95 % CI : 1.434.37 , P=0.001 ) ; WHO performance status ( HR=1.47 , 95 % CI : 1.10 - 1.96 , P=0.008 ) ; and number of metastatic sites ( HR=1.30 , 95 % CI : 1.05 - 1.60 , P=0.014 ) . CONCLUSION This analysis of a r and om population of IRMCRC patients supports Cx efficacy and feasibility , and is in agreement with the results of the BOND study Introduction : Despite the extensive clinical experience with irinotecan , significant concerns remain regarding its toxicity . In a phase I trial , we modulated irinotecan pharmacokinetics by inhibiting biliary excretion of SN-38 , the active metabolite of irinotecan , using cyclosporine . The modulation appeared to decrease the gastrointestinal toxicity of irinotecan and suggested that irinotecan activity might also be retained . Hence , we conducted this phase II trial in patients with colorectal cancer ( CRC ) to further evaluate the toxicity and activity of irinotecan modulated with cyclosporine . Patients and Methods : Sixteen patients with 5-fluorouracil refractory CRC were treated .  Cyclosporine ( 5 mg/kg ) was administered as a 6-h infusion and irinotecan ( 60 mg/m2/day , 90-min infusion ) was started 3 h after initiation of the Cyclosporine . Both agents were given weekly for 4 weeks , every 6 weeks . Responses were assessed every 12 weeks , and toxicity was monitored weekly . Results : Sixteen patients were evaluable for toxicity and 11 for response . There was 1 partial response ( 6 % ) . Five patients had SD lasting a median of 12 weeks . Grade 3/4 diarrhea was observed in only 13 % of the patients . Conclusion : Pharmacokinetic modulation of irinotecan using parenteral cyclosporine appears to decrease the incidence of diarrhea in CRC patients . Given the modest activity of irinotecan monotherapy , a larger study would be required to assess if the modulation improves the toxicity without compromising this activity . The available clinical data suggest that pharmacokinetic modulation of irinotecan should be evaluated further to define its optimal clinical utility Goals of workTargeted monoclonal antibodies ( MoAbs ) have become a promising treatment option for patients with cancer . However , there is a risk of developing infusion reactions ( IRs ) with MoAbs . This study was conducted to evaluate the impact of IRs on staff time and costs among patients receiving an initial infusion of cetuximab ( Erbitux ® ) and rituximab ( Rituxan ® ) . Patients and methods A prospect i ve multicenter study involving time and motion and activity sampling methods was conducted among patients with cancer receiving their first outpatient infusion of cetuximab or rituximab .  Patients were observed from initiation of MoAb infusion to the end of the clinic visit . IRs were classified as absent , mild/moderate , and severe/life threatening . Staff time and costs were estimated for preparation and administration of MoAb , other chemotherapy agents , and for management of IRs . Re source costs were compared across IR groups within each MoAb . Main results Among 161 patients enrolled , 32 % of 71 patients on cetuximab and 39 % of 90 patients on rituximab experienced IRs . Treatment of patients who experienced IRs required more staff time ( 31–80 % more time ) and result ed in higher human re source costs ( increase of 17–65 US dollars ) than patients who did not experience IRs . Conclusions IRs following cetuximab and rituximab administration are common and are associated with measurably increased costs of care . The frequency of IRs suggests the importance of identifying clinical guidelines for intervention and management PURPOSE We evaluated the safety and efficacy of concurrent administration of two monoclonal antibodies , cetuximab and bevacizumab , in patients with metastatic colorectal cancer . PATIENTS AND METHODS This was a r and omized phase II study in patients with irinotecan-refractory colorectal cancer . All patients were naïve to both bevacizumab and cetuximab .  Patients in arm A received irinotecan at the same dose and schedule as last received before study entry , plus cetuximab 400 mg/m2 loading dose , then weekly cetuximab 250 mg/m2 , plus bevacizumab 5 mg/kg administered every other week . Patients in arm B received the same cetuximab and bevacizumab as those in arm A but without irinotecan . RESULTS Forty-three patients received cetuximab , bevacizumab , and irinotecan ( CBI ) and 40 patients received cetuximab and bevacizumab  alone ( CB ) . Toxicities were as would have been expected from the single agents . For the CBI arm , time to tumor progression ( TTP ) was 7.3 months and the response rate was 37 % ; for the CB arm , TTP was 4.9 months and the response rate was 20 % . The overall survival for the CBI arm was 14.5 months and the overall survival for the CB-alone arm was 11.4 months . CONCLUSION Cetuximab and bevacizumab can be administered concurrently , with a toxicity pattern that seems to be similar to that which would be expected from the two agents alone . This combination plus irinotecan also seems to be feasible . The activity seen with the addition of bevacizumab to cetuximab , or to cetuximab plus irinotecan , seems to be favorable when compared with historical controls of cetuximab or cetuximab/irinotecan in patients who are naïve to bevacizumab PURPOSE To evaluate the antitumor activity and toxicity of single-agent cetuximab in patients with chemotherapy-refractory colorectal cancer whose tumors express the epidermal growth factor receptor . PATIENTS AND METHODS Phase II , open-label clinical trial . Patients were required to have EGFr expression demonstrated on formalin-fixed paraffin-embedded tumor tissue by immunohistochemical staining before study participation . Patients were required to have received irinotecan , either alone or in a combination regimen , and to have demonstrated clinical failure on this regimen before study entry . Cetuximab was administered weekly by intravenous infusion . The first dose of 400 mg/m(2 ) was given during the course of 2 hours . Subsequent weekly treatments were given at a dose of 250 mg/m(2 ) during the course of 1 hour . RESULTS Fifty-seven eligible patients were treated . All were assessable for toxicity and response . The most commonly encountered grade 3 to 4 adverse events , regardless of relationship to study drug , were an acne-like skin rash , predominantly on the face and upper torso ( 86 % with any grade ; 18 % with grade 3 ) , and a composite of asthenia , fatigue , malaise , or lethargy ( 56 % with any grade , 9 % with grade 3 ) . Two patients ( 3.5 % ) experienced grade 3 allergic reactions requiring discontinuation of study treatment . A third patient experienced a grade 3 allergic reaction that resolved , and the patient continued on the study . Neither diarrhea nor neutropenia were dose limiting in any of the 57 patients treated . Five patients ( 9 % ; 95 % CI , 3 % to 19 % ) achieved a partial response . Twenty-one additional patients had stable disease or minor responses . The median survival in these previously treated patients with chemotherapy-refractory colorectal cancer is 6.4 months . CONCLUSION Cetuximab on this once-weekly schedule has modest activity and is well-tolerated as a single agent in patients with chemotherapy-refractory colorectal cancer whose tumors express the epidermal growth factor receptor . Further studies of cetuximab will evaluate the use of cetuximab in conjunction with first-line and adjuvant treatments for this disease 
    Output:
    
The incidence of IRs varies among different mAbs ; and IRs may cause treatment disruption and require costly medical interventions