***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 
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    Input: Erlotinib combined with gemcitabine has not been evaluated in Japanese patients with unresectable pancreatic cancer . This two‐step phase II study assessed the safety and pharmacokinetics of erlotinib 100 mg/day ( oral ) plus gemcitabine 1000 mg/m2 ( i.v . days 1 , 8 , 15 ) in a 28‐day cycle in the first step , and efficacy and safety in the second step . The primary end‐point was safety . One hundred and seven patients were enrolled ( first step , n = 6 ; second step , n = 101 ) . The most common adverse event was RASH ( compiled using the preferred terms rash , acne , exfoliative rash , dermatitis acneiform , erythema , eczema , dermatitis and pustular rash ) in 93.4 % of patients . One treatment‐related death occurred . While interstitial lung disease‐like events were reported in nine patients ( 8.5 % ; grade 1/2/3 , 3.8/2.8/1.9 % ) , all patients recovered or improved . The median overall survival , the 1‐year survival rate and median progression‐free survival were 9.23 months , 33.0 % and 3.48 months , respectively . The overall response and disease control rates were 20.3 % and 50.0 % , respectively . In Japanese patients with unresectable pancreatic cancer  , erlotinib plus gemcitabine  had acceptable toxicity and efficacy that was not inferior to that seen in Western patients . ( Cancer Sci 2011 ; 102 : 425–431 Objectives This retrospective study examined pancreatic cancer patients who received combination gemcitabine and erlotinib  to determine if the association between rash and outcomes observed in clinical trials would be observed in ‘ real-world ’ community oncology setting s. Methods Medical records from 10 community oncology practice s were used to identify eligible patients . Rash severity was classified as High ( moderate/severe ) versus Low ( absent/mild ) based on medical record review . Kaplan-Meier analysis assessed progression-free survival ( PFS ) and overall survival ( OS ) by rash status from a l and mark of 42 days after treatment initiation . Cox regression with time-varying covariates tested whether high-severity rash predicted longer OS and PFS . Results The High Severity group ( n = 34 ) had longer median OS from the l and mark than the Low Severity group ( n = 134 ; 7.58 months vs 5.03 months , P = 0.0339 ) . Cox regression analysis ( n = 174 ) confirmed a reduced risk of death with High Rash Severity ( hazard ratio [ HR ] = 0.67 , P = 0.0389 ) . Progression-free survival results showed a similar pattern ( median PFS 2.37 months from l and mark vs 2.04 months for High vs Low Severity groups , P = 0.0485 ) . Conclusions Results from this community sample were consistent with findings from r and omized clinical trials , showing that longer OS is predicted by high-severity rash in erlotinib-treated pancreatic cancer patients BACKGROUND Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics : both tumour shrinkage ( objective response ) and disease progression are useful endpoints in clinical trials . Since RECIST was published in 2000 , many investigators , cooperative groups , industry and government authorities have adopted these criteria in the assessment of treatment outcomes . However , a number of questions and issues have arisen which have led to the development of a revised RECIST guideline ( version 1.1 ) . Evidence for changes , summarised in separate papers in this special issue , has come from assessment of a large data warehouse ( > 6500 patients ) , simulation studies and literature review s. HIGHLIGHTS OF REVISED RECIST 1.1 : Major changes include : Number of lesions to be assessed : based on evidence from numerous trial data bases merged into a data warehouse for analysis purpose s , the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total ( and from five to two per organ , maximum ) . Assessment of pathological lymph nodes is now incorporated : nodes with a short axis of 15 mm are considered measurable and assessable as target lesions . The short axis measurement should be included in the sum of lesions in calculation of tumour response . Nodes that shrink to < 10 mm short axis are considered normal . Confirmation of response is required for trials with response primary endpoint but is no longer required in r and omised studies since the control arm serves as appropriate means of interpretation of data . Disease progression is clarified in several aspects : in addition to the previous definition of progression in target disease of 20 % increase in sum , a 5 mm absolute increase is now required as well to guard against over calling PD when the total sum is very small . Furthermore , there is guidance offered on what constitutes ' unequivocal progression ' of non-measurable/non-target disease , a source of confusion in the original RECIST guideline . Finally , a section on detection of new lesions , including the interpretation of FDG-PET scan assessment is included . Imaging guidance : the revised RECIST includes a new imaging appendix with up date d recommendations on the optimal anatomical assessment of lesions . FUTURE WORK A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI . It was concluded that , at present , there is not sufficient st and ardisation or evidence to ab and on anatomical assessment of tumour burden . The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression . As is detailed in the final paper in this special issue , the use of these promising newer approaches requires appropriate clinical validation studies BACKGROUND In a phase 1 - 2 trial of albumin-bound paclitaxel ( nab-paclitaxel ) plus gemcitabine , substantial clinical activity was noted in patients with advanced pancreatic cancer . We conducted a phase 3 study of the efficacy and safety of the combination versus gemcitabine monotherapy in patients with metastatic pancreatic cancer . METHODS We r and omly assigned patients with a Karnofsky performance-status score of 70 or more ( on a scale from 0 to 100 , with higher scores indicating better performance status ) to nab-paclitaxel ( 125 mg per square meter of body-surface area ) followed by gemcitabine  ( 1000 mg per square meter ) on days 1 , 8 , and 15 every 4 weeks or gemcitabine monotherapy ( 1000 mg per square meter ) weekly for 7 of 8 weeks ( cycle 1 ) and then on days 1 , 8 , and 15 every 4 weeks ( cycle 2 and subsequent cycles ) . Patients received the study treatment until disease progression . The primary end point was overall survival ; secondary end points were progression-free survival and overall response rate . RESULTS A total of 861 patients were r and omly assigned to nab-paclitaxel plus gemcitabine ( 431 patients ) or gemcitabine  ( 430 ) . The median overall survival was 8.5 months in the nab-paclitaxel-gemcitabine group as compared with 6.7 months in the gemcitabine group ( hazard ratio for death , 0.72 ; 95 % confidence interval [ CI ] , 0.62 to 0.83 ; P<0.001 ) . The survival rate was 35 % in the nab-paclitaxel-gemcitabine group versus 22 % in the gemcitabine group at 1 year , and 9 % versus 4 % at 2 years . The median progression-free survival was 5.5 months in the nab-paclitaxel-gemcitabine group , as compared with 3.7 months in the gemcitabine group ( hazard ratio for disease progression or death , 0.69 ; 95 % CI , 0.58 to 0.82 ; P<0.001 ) ; the response rate according to independent review was 23 % versus 7 % in the two groups ( P<0.001 ) . The most common adverse events of grade 3 or higher were neutropenia ( 38 % in the nab-paclitaxel-gemcitabine group vs. 27 % in the gemcitabine group ) , fatigue ( 17 % vs. 7 % ) , and neuropathy ( 17 % vs. 1 % ) . Febrile neutropenia occurred in 3 % versus 1 % of the patients in the two groups . In the nab-paclitaxel-gemcitabine group , neuropathy of grade 3 or higher improved to grade 1 or lower in a median of 29 days . CONCLUSIONS In patients with metastatic pancreatic adenocarcinoma , nab-paclitaxel plus gemcitabine significantly improved overall survival , progression-free survival , and response rate , but rates of peripheral neuropathy and myelosuppression were increased . ( Funded by Celgene ; Clinical Trials.gov number , NCT00844649 . ) Purpose To evaluate the feasibility , toxicity and efficacy of the combination regimen consisting of gemcitabine-FDR infusion plus erlotinib , in ACP patients . Methods Forty-two patients with histologically confirmed , locally advanced or metastatic pancreatic cancer were included in this phase II trial . Main objectives were to assess the efficacy and safety of this regimen . Therapeutic regimen consisted of gemcitabine 1,200 mg/m2 in 120-min infusion on days 1 , 8 and 15 , plus erlotinib 100 mg orally once daily . Cycles were repeated every 28 days . Results A total of 160 courses of gemcitabine-FDR erlotinib were administered ( median 3.8 courses per patient ) . The most common grade 3–4 AEs were neutropenia ( 21 % ) , thrombocytopenia ( 10 % ) , skin rash ( 10 % ) and asthenia ( 10 % ) . Complete response was achieved in one patient ( 2 % ) and 11 ( 26 % ) achieved a partial response . Stable disease and progression disease were observed in 11 patients ( 26 % ) and 19 ( 45 % ) , respectively . Median time to progression was 5 months ( 95%CI : 3.9–5.8 months ) and median overall survival was 8 months ( 95 % CI : 5.1–10.8 ) . One-year survival rate was 35 % . Conclusions A regimen consisting of gemcitabine-FDR infusion plus erlotinib is active and well tolerated in APC patients . However , the results do not justify the conduct of a Phase III trial Objective To analyze the efficacy of gemcitabine with or without erlotinib for pancreatic cancer , and to determine the predictive role of epidermal growth factor receptor ( EGFR ) and KRAS mutations in these patients . Methods This was a single-center , r and omized , open-label , prospect i ve trial . Eighty-eight chemotherapy-naïve metastatic pancreatic cancer patients were r and omized for treatment with gemcitabine or gemcitabine plus erlotinib . EGFR and KRAS mutations were analyzed , respectively . The primary endpoint was the disease control rate . Results Disease control rate ( 64 % vs. 25 % ; P < 0.001 ) , progression-free survival ( median 3.8 vs. 2.4 months ; P < 0.001 ) , and overall survival ( median 7.2 vs. 4.4 months ; P < 0.001 ) were better in the gemcitabine plus erlotinib group than in the gemcitabine alone group . In the gemcitabine plus erlotinib group , disease control ( 85 % vs. 33 % ; P = 0.001 ) , progression-free survival ( median 5.9 vs. 2.4 months ; P = 0.004 ) , and overall survival ( median 8.7 vs. 6.0 months ; P = 0.044 ) were better in patients with EGFR mutations than in those without EGFR mutations . KRAS mutation was not associated with treatment response or survival . Conclusions Gemcitabine plus erlotinib is more effective than gemcitabine alone for treating metastatic pancreatic cancer patients , especially those with EGFR mutations . Clinical Trials.gov number , NCT01608841 We report on the results of a prospect i ve treatment of 30 proven metastatic pancreatic cancer patients with the recently described combination of gemcitabine and erlotinib ( GEM+E ) ( 24 × 1st line therapy , 8 × 2nd line therapy ) . Eight of these patients received GEM+E for treatment of metastastic tumour recurrence after previous resective surgery , followed by adjuvant chemotherapy with gemcitabine . In 2 patients GEM+E was given as 1st line treatment and later , after complete response which was followed by a new recurrence , also as a second line therapy . The evaluation of RASH severity grade s , the course of the serum tumour marker CA19 - 9 were determined every 14 days and the evaluation of the imaging methods CT or MRT , evaluated every 6 - 8 weeks , revealed the following results : there was a tendency for RASH grade s to correlate with the tumour response , however , with observed exceptions . The decision for interruption or maintenance of GEM+E , therefore , should not be based on the RASH phenomenon , but on a detailed follow-up with imaging methods and 
    Output:
    
Conclusion Skin rash was associated with better OS and PFS in APC patients treated with gemcitabine plus erlotinib .