***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 Erlotinib and gefitinib are weak base drugs whose absorption and clinical efficacy may be impaired by concomitant gastric acid suppressive ( AS ) therapy , yet proton pump inhibitors ( PPIs ) and histamine-2 receptor antagonists ( H2As ) are widely indicated in non-small cell lung cancer ( NSCLC ) patients for the prevention and treatment of erlotinib-induced gastrointestinal injury and corticosteroid-associated gastric irritation . We assessed the clinical relevance of this potential drug-drug interaction ( DDI ) in a retrospective cohort of EGFR-mutant NSCLC patients . Results The AS usage rate was 35 % . In the overall cohort , AS users did not experience poorer OS ( HR : 1.47 , 95 % CI : 0.92 – 2.35 , P = 0.10 ; median , 11.4 versus 17.5 months ) or PFS ( HR = 1.37 , 95 % CI : 0.89 – 2.12 , P = 0.16 ; median , 7.6 versus 8.7 months ) compared with non-users in multivariate Cox regression analysis . However , subgroup analyses indicated that AS usage was associated with significantly poorer OS and PFS in patients who had fewer or milder comorbidities ( Charlson comorbidity index ≤ 2 ) , those with Karnofsky performance status < 90 , and never-smokers . Material s and Methods A retrospective data base analysis of 157 patients given erlotinib or gefitinib for EGFR-mutant advanced NSCLC from two institutions was conducted . Patients were classified as AS-users if the periods of AS and anti-EGFR therapy overlapped by ≥ 30 % . Overall survival ( OS ) and progression-free survival ( PFS ) were assessed according to AS usage . Conclusions Concomitant AS therapy did not have an adverse impact on OS and /or PFS in the overall cohort . Our subgroup findings should be regarded exploratory and require replication in a large prospect i ve cohort BACKGROUND Non-small-cell lung cancer with sensitive mutations of the epidermal growth factor receptor ( EGFR ) is highly responsive to EGFR tyrosine kinase inhibitors such as gefitinib , but little is known about how its efficacy and safety profile compares with that of st and ard chemotherapy . METHODS We r and omly assigned 230 patients with metastatic , non-small-cell lung cancer and EGFR mutations who had not previously received chemotherapy to receive gefitinib or carboplatin-paclitaxel .  The primary end point was progression-free survival ; secondary end points included overall survival , response rate , and toxic effects . RESULTS In the planned interim analysis of data for the first 200 patients , progression-free survival was significantly longer in the gefitinib group than in the st and ard-chemotherapy group ( hazard ratio for death or disease progression with gefitinib , 0.36 ; P<0.001 ) , result ing in early termination of the study . The gefitinib group had a significantly longer median progression-free survival ( 10.8 months , vs. 5.4 months in the chemotherapy group ; hazard ratio , 0.30 ; 95 % confidence interval , 0.22 to 0.41 ; P<0.001 ) , as well as a higher response rate ( 73.7 % vs. 30.7 % , P<0.001 ) . The median overall survival was 30.5 months in the gefitinib group and 23.6 months in the chemotherapy group ( P=0.31 ) . The most common adverse events in the gefitinib group were rash ( 71.1 % ) and elevated aminotransferase levels ( 55.3 % ) , and in the chemotherapy group , neutropenia ( 77.0 % ) , anemia ( 64.6 % ) , appetite loss ( 56.6 % ) , and sensory neuropathy ( 54.9 % ) . One patient receiving gefitinib  died from interstitial lung disease . CONCLUSIONS First-line gefitinib for patients with advanced non-small-cell lung cancer who were selected on the basis of EGFR mutations improved progression-free survival , with acceptable toxicity , as compared with st and ard chemotherapy . ( UMIN-CTR number , C000000376 . BACKGROUND Proton pump inhibitors ( ppis ) are a commonly used medication . A limited number of studies have identified a weak-to-moderate association between ppi use and colorectal cancer ( crc ) risk , but none to date have identified an effect of ppi use on crc survival . We therefore postulated that an association between ppi use and crc survival might potentially exist . METHODS We performed a retrospective chart review of 1304 crc patients diagnosed from January 2005 to December 2011 and treated at the Cancer Centre of Southeastern Ontario . Kaplan-Meier analysis and Cox proportional hazards regression models were used to evaluate overall survival ( os ) . RESULTS We identified 117 patients ( 9.0 % ) who were taking ppis at the time of oncology consult . Those taking a ppi were also more often taking asa or statins  ( or both ) and had a statistically significantly increased rate of cardiac disease . No identifiable difference in tumour characteristics was evident in the two groups , including tumour location , differentiation , lymph node status , and stage . Univariate analysis identified a statistically nonsignificant difference in survival , with those taking a ppi experiencing lesser 1-year ( 82.1 % vs. 86.7 % , p = 0.161 ) , 2-year ( 70.1 % vs. 76.8 % , p = 0.111 ) , and 5-year os ( 55.2 % vs. 62.9 % , p = 0.165 ) . When controlling for patient demographics and tumour characteristics , multivariate Cox regression analysis identified a statistically significant effect of ppi in our patient population ( hazard ratio : 1.343 ; 95 % confidence interval : 1.011 to 1.785 ; p = 0.042 ) . CONCLUSIONS Our results suggest a potential adverse effect of ppi use on os in crc patients . These results need further evaluation in prospect i ve analyses BACKGROUND Erlotinib has been shown to improve progression-free survival compared with chemotherapy when given as first-line treatment for Asian patients with non-small-cell lung cancer ( NSCLC ) with activating EGFR mutations . We aim ed to assess the safety and efficacy of erlotinib compared with st and ard chemotherapy for first-line treatment of European patients with advanced EGFR-mutation positive NSCLC . METHODS We undertook the open-label , r and omised phase 3 EURTAC trial at 42 hospitals in France , Italy , and Spain . Eligible participants were adults ( > 18 years ) with NSCLC and EGFR mutations ( exon 19 deletion or L858R mutation in exon 21 ) with no history of chemotherapy for metastatic disease ( neoadjuvant or adjuvant chemotherapy ending ≥ 6 months before study entry was allowed ) . We r and omly allocated participants ( 1:1 ) according to a computer-generated allocation schedule to receive oral erlotinib 150 mg per day or 3 week cycles of st and ard intravenous chemotherapy of cisplatin 75 mg/m(2 ) on day 1 plus docetaxel ( 75 mg/m(2 ) on day 1 ) or gemcitabine ( 1250 mg/m(2 ) on days 1 and 8) . Carboplatin ( AUC 6 with docetaxel 75 mg/m(2 ) or AUC 5 with gemcitabine 1000 mg/m(2 ) ) was allowed in patients unable to have cisplatin . Patients were stratified by EGFR mutation type and Eastern Cooperative Oncology Group performance status ( 0 vs 1 vs 2 ) . The primary endpoint was progression-free survival ( PFS ) in the intention-to-treat population . We assessed safety in all patients who received study drug ( ≥ 1 dose ) . This study is registered with Clinical Trials.gov , number NCT00446225 . FINDINGS Between Feb 15 , 2007 , and Jan 4 , 2011 , 174 patients with EGFR mutations were enrolled . One patient received treatment before r and omisation and was thus withdrawn from the study ; of the remaining patients , 86 were r and omly assigned to receive erlotinib and 87 to receive st and ard chemotherapy . The preplanned interim analysis showed that the study met its primary endpoint ; enrolment was halted , and full evaluation of the results was recommended . At data cutoff ( Jan 26 , 2011 ) , median PFS was 9·7 months ( 95 % CI 8·4 - 12·3 ) in the erlotinib group , compared with 5·2 months ( 4·5 - 5·8 ) in the st and ard chemotherapy group ( hazard ratio 0·37 , 95 % CI 0·25 - 0·54 ; p < 0·0001 ) . Main grade 3 or 4 toxicities were rash ( 11 [ 13 % ] of 84 patients given erlotinib vs none of 82 patients in the chemotherapy group ) , neutropenia ( none vs 18 [ 22 % ] ) , anaemia ( one [ 1 % ] vs three [ 4 % ] ) , and increased amino-transferase concentrations ( two [ 2 % ] vs 0 ) . Five ( 6 % ) patients on erlotinib  had treatment-related severe adverse events compared with 16 patients ( 20 % ) on chemotherapy . One patient in the erlotinib group and two in the st and ard chemotherapy group died from treatment-related causes . INTERPRETATION Our findings strengthen the rationale for routine baseline tissue-based assessment of EGFR mutations in patients with NSCLC and for treatment of mutation-positive patients with EGFR tyrosine-kinase inhibitors . FUNDING Spanish Lung Cancer Group , Roche Farma , Hoffmann-La Roche , and Red Temática de Investigacion Cooperativa en Cancer Temozolomide , a new oral cytotoxic agent , has been given to 28 patients with primary brain tumours . Treatment was given at a dose of 150 mg/m2/day for 5 days ( i.e. total dose 750 mg/m2 ) escalating , if no significant myelosuppression was noted on day 22 , to 200 mg/m2/day for 5 days ( i.e. total dose 1000 mg/m2 ) for subsequent courses at 4 week intervals . A major improvement in computer tomography ( CT ) scan was noted in 5/10 patients with astrocytomas recurrent after radiotherapy , with a major clinical improvement but minor improvement on CT scan in one further patient . Reduction in the size of the CT lesion was also observed in 4/7 patients with newly diagnosed high grade astrocytomas given 2 - 3 courses of temozolomide prior to irradiation . 1 patient with recurrent medulloblastoma had a clinical response in bone metastases . Temozolomide was well tolerated with little subjective toxicity and usually predictable myelosuppression and is a promising new drug in the treatment of primary brain tumours PURPOSE Erlotinib depends on stomach pH for its bioavailability . When erlotinib is taken concurrently with a proton pump inhibitor ( PPI ) , stomach pH increases , which results in a clinical ly relevant decrease of erlotinib bioavailability . We hypothesized that this drug-drug interaction is reversed by taking erlotinib with the acidic beverage cola . The effects of cola on erlotinib bioavailability in patients not treated with a PPI were also studied . PATIENTS AND METHODS In this r and omized , cross-over , pharmacokinetic study in patients with non-small-cell lung cancer , we studied intrapatient differences in absorption ( area under the plasma concentration time curve [ AUC0 - 12h ] ) after a 7-day period of concomitant treatment with erlotinib , with or without esomeprazole , with either cola or water . At the 7th and 14th day , patients were hospitalized for 1 day for pharmacokinetic sampling . RESULTS Twenty-eight evaluable patients were included in the analysis . In patients treated with erlotinib and esomeprazole with cola , the mean AUC0 - 12h increased 39 % ( range , -12 % to 136 % ; P = .004 ) , whereas in patients not treated with the PPI , the mean AUC0 - 12h was only slightly higher ( 9 % ; range , -10 % to + 30 % ; P = .03 ) after erlotinib intake with cola . CONCLUSION Cola intake led to a clinical ly relevant and statistically significant increase in the bioavailability of erlotinib during esomeprazole treatment . In patients not treated with the PPI , the effects of cola were marginal . These findings can be used to optimize the management of drug-drug interactions between PPIs and erlotinib Purpose Several cases have been reported in which central nervous system ( CNS ) metastases of non-small cell lung cancer ( NSCLC ) resistant to gefitinib were improved by erlotinib . However , there has been no study in which cerebrospinal fluid ( CSF ) concentrations of gefitinib and erlotinib 
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Only studies of EGFR ( epidermal growth factor receptor ) mutated NSCLC patients receiving TKIs and those with colorectal cancer receiving oral chemotherapy showed a significant correlation between GAS and poor survival .
Our study supports the evidence of a possible negative impact of concomitant GAS therapy on survival outcomes of patients receiving oral anti-cancer drugs