Systemic Therapy for Stage IV Non-Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. Treatment of stage III non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Treatment of stage II non-small cell lung cancer. Subsequent chemotherapy improves survival outcome in advanced non-small-cell lung cancer with acquired tyrosine kinase inhibitor resistance. Sequential chemoradiotherapy versus radiotherapy in the management of locally advanced non-small-cell lung cancer Protocol for the CONVERT trial—Concurrent ONce-daily VErsus twice-daily RadioTherapy: an international 2-arm randomised controlled trial of concurrent chemoradiotherapy comparing twice-daily and once-daily radiotherapy schedules in patients with limited stage small cell lung cancer (LS-SCLC) and goo Erlotinib Monotherapy for Stage IIIB/IV Non-small Cell Lung Cancer: A Multicenter Trial by the Korean Cancer Study Group A multicenter, open-label, phase II trial of S-1 plus carboplatin in advanced non-small cell lung cancer patients with interstitial lung disease. Randomized controlled trial of S-1 versus docetaxel in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy (East Asia S-1 Trial in Lung Cancer) Prognostic Factors and Survival in Non-Small Cell Lung Cancer Patients Treated with Chemoradiotherapy Systemic Therapy for Stage IV Non-Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. Impact of new chemotherapeutic and targeted agents on survival in stage IV non-small cell lung cancer. Phase III trial of two versus four additional cycles in patients who are nonprogressive after two cycles of platinum-based chemotherapy in non small-cell lung cancer. Eligibility of patients with advanced non-small cell lung cancer for phase III chemotherapy trials Dose escalation of accelerated hypofractionated three-dimensional conformal radiotherapy (at 3 Gy/fraction) with concurrent vinorelbine and carboplatin chemotherapy in unresectable stage III non-small-cell lung cancer: a phase I trial Phase I clinical and pharmacokinetic study of sorafenib in combination with carboplatin and paclitaxel in patients with advanced non–small cell lung cancer Phase I study of ipilimumab in phased combination with paclitaxel and carboplatin in Japanese patients with non-small-cell lung cancer
Purpose Provide evidence -based recommendations updating the 2015 ASCO guideline on systemic therapy for patients with stage IV non-small-cell lung cancer ( NSCLC ) . Methods The ASCO NSCLC Expert Panel made recommendations based on a systematic review of r and omized controlled trials from February 2014 to December 2016 plus the Cancer Care Ontario Program in Evidence -Based Care 's up date of a previous ASCO search . Results This guideline up date reflects changes in evidence since the previous guideline up date . Fourteen r and omized controlled trials provide the evidence base ; earlier phase trials also informed recommendation development . Recommendations New or revised recommendations include the following . Regarding first-line treatment for patients with non-squamous cell carcinoma or squamous cell carcinoma ( without positive markers , eg , EGFR/ALK /ROS1 ) , if the patient has high programmed death lig and 1 ( PD-L1 ) expression , pembrolizumab should be used alone ; if the patient has low PD-L1 expression , clinicians should offer st and ard chemotherapy . All other clinical scenarios follow 2015 recommendations . Regarding second-line treatment in patients who received first-line chemotherapy  , without prior immune checkpoint therapy , if NSCLC tumor is positive for PD-L1 expression , clinicians should use single-agent nivolumab , pembrolizumab , or atezolizumab ; if tumor has negative or unknown PD-L1 expression , clinicians should use nivolumab or atezolizumab . All immune checkpoint therapy is recommended alone plus in the absence of contraindications . For patients who received a prior first-line immune checkpoint inhibitor , clinicians should offer st and ard chemotherapy . For patients who can not receive immune checkpoint inhibitor after chemotherapy , docetaxel is recommended ; in patients with nonsquamous NSCLC , pemetrexed is recommended . In patients with a sensitizing EGFR mutation , disease progression after first-line epidermal growth factor receptor tyrosine kinase inhibitor therapy , and T790 M mutation , osimertinib is recommended ; if NSCLC lacks the T790 M mutation , then chemotherapy is recommended . Patients with ROS1 gene rearrangement without prior crizotinib may be offered crizotinib , or if they previously received crizotinib , they may be offered chemotherapy OBJECTIVES Stage III non-small cell lung cancer ( NSCLC ) describes a heterogeneous population with disease presentation ranging from apparently resectable tumors with occult microscopic nodal metastases to unresectable , bulky nodal disease . This review up date s the published clinical trials since the last American College of Chest Physicians guidelines to make treatment recommendations for this controversial subset of patients . METHODS Systematic search es were conducted through MEDLINE , Embase , and the Cochrane Data base for Systematic Review up to December 2011 , focusing primarily on r and omized trials , selected meta-analyses , practice guidelines , and review s. RESULTS For individuals with stage IIIA or IIIB disease , good performance scores , and minimal weight loss , treatment with combined chemoradiotherapy results in better survival than radiotherapy alone . Consolidation chemotherapy or targeted therapy following definitive chemoradiation for stage IIIA is not supported . Neoadjuvant therapy followed by surgery is neither clearly better nor clearly worse than definitive chemoradiation . Most of the arguments made regarding patient selection for neoadjuvant therapy and surgical resection provide evidence for better prognosis but not for a beneficial impact of this treatment strategy ; however , weak comparative data suggest a possible role if only lobectomy is needed in a center with a low perioperative mortality rate . The evidence supports routine platinum-based adjuvant chemotherapy following complete resection of stage IIIA lung cancer encountered unexpectedly at surgery . Postoperative radiotherapy  improves local control without improving survival . CONCLUSIONS Multimodality therapy is preferable in most subsets of patients with stage III lung cancer . Variability in the patients included in r and omized trials limits the ability to combine results across studies and thus limits the strength of recommendations in many scenarios . Future trials are needed to investigate the roles of individualized chemotherapy , surgery in particular cohorts or setting s , prophylactic cranial radiation , and adaptive radiation Based on clinical assessment alone , patients with stage II non-small cell lung cancer ( NSCLC ) comprise only 5 % of all patients with NSCLC . In addition , patients with stage II NSCLC represent a heterogeneous group , since stage II consists of patients with T1 - 2N1 or T3N0 tumors . By definition , patients with tumor invading the chest wall apex , mediastinum , diaphragm , or even the mainstem bronchus may all have T3 tumors . The extent of the data available regarding treatment of each of these different groups is therefore limited . The quality of the data is limited as well , because information often comes from small series of patients . Studies of adjuvant therapy after complete resection of stage II NSCLC are an important exception to this generalization , since data from large , r and omized studies of adjuvant radiation therapy , chemotherapy , or a combination of the two are available for analysis . Superior sulcus tumors are discussed elsewhere in these guidelines BACKGROUND Epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitors ( TKIs ) provide promising effect against non-small-cell lung cancer ( NSCLC ) , although most tumors acquire resistance . Our objective was to assess the survival outcome of patients with NSCLC with or without subsequent chemotherapy after acquired TKI resistance . PATIENTS AND METHODS A total of 114 patients with pathologically confirmed stage IIIB or IV NSCLC who had had disease control with TKIs were retrospectively review ed . After acquired TKI resistance , patients received either best supportive care ( BSC ) only or BSC plus subsequent chemotherapy . Both groups were well balanced in regard to performance status , age , sex , histology subtype , and smoking status . RESULTS Sixty-seven patients ( 58.8 % ) received subsequent chemotherapy , and 47 patients ( 41.2 % ) received BSC only . The median overall survival ( OS ) and progression-free survival ( PFS ) from the time of TKI resistance in the subsequent-chemotherapy group ( 11.2 months and 3.5 months , respectively ) were longer than those of the BSC group ( 3.8 months and 1.5 months , respectively ; P < .01 ) . Patients who subsequently received taxane-based chemotherapy exhibited higher a response rate and disease control rate ( 48.7 % and 79.5 % , respectively ) than patients treated with a nontaxane regimen ( 21.4 % and 53.5 % , respectively ; P < .05 ) . Overall survival and PFS in patients after taxane-based subsequent chemotherapy ( 12.7 months and 5.1 months , respectively ) were longer than those of patients given a nontaxane regimen ( 7 months and 1.8 months , respectively ; P < .01 ) . CONCLUSION This study suggests that acquired TKI resistance should be managed aggressively . The higher antitumor response and survival outcome with a taxane-based regimen in this retrospective study could encourage further prospect i ve investigation to confirm the efficacy of taxane over nontaxane chemotherapy in patients with NSCLC whose disease progresses with EGFR TKI treatment This prospect i ve r and omized trial compared neoadjuvant chemotherapy followed by local-regional radiotherapy ( study group ) with radiotherapy alone ( control group ) in 506 patients with locally advanced non-small-cell lung cancer . The study group received three cycles of cisplatin , ifosfamide with Mesna , and mitomycin C at 21-day intervals . Radiotherapy was delivered up to a dose of 60 Gy . Evaluable patients numbered 460 . In the study group , 228 patients were assessed for tumor response after chemotherapy : 13 ( 5.7 % ) had a complete response ; 103 ( 43.2 % ) , a partial response ; 48 ( 21 % ) showed no change ; and 74 patients ( 31.1 % ) had progressive disease . These patients then received chest irradiation , which was well tolerated . On completion of radiotherapy , 16.2 % of the study group and 6 % of the control group had a complete response . No change was seen in 10.1 % of study patients and 15.5 % of control patients . Respective rates for disease progression were 27.6 % and 42.3 % . Actuarial 2-year survival was 20 % in the study group and 7.4 % in the control group Introduction Concurrent ONce-daily VErsus twice-daily RadioTherapy ( CONVERT ) is the only multicentre , international , r and omised , phase III trial open in Europe and Canada looking at optimisation of chemoradiotherapy ( RT ) in limited stage small cell lung cancer ( LS-SCLC ) . Following on from the Turrisi trial of once-daily versus twice-daily ( BD ) concurrent chemoradiotherapy , there is a real need for a new phase III trial using modern conformal RT techniques and investigating higher once-daily radiation dose . This trial has the potential to define a new st and ard chemo-RT regimen for patients with LS-SCLC and good performance status . Methods and analysis 447 patients with histologically or cytologically proven diagnosis of SCLC were recruited from 74 centres in eight countries between 2008 and 2013 . Patients were r and omised to receive either concurrent twice-daily RT(45 Gy in 30 twice-daily fractions over 3 weeks ) or concurrent once-daily RT(66 Gy in 33 once-daily fractions over 6.5 weeks ) both starting on day 22 of cycle 1 . Patients are followed up until death . The primary end point of the study is overall survival and secondary end points include local progression-free survival , metastasis-free survival , acute and late toxicity based on the Common Terminology Criteria for Adverse Events V.3.0 , chemotherapy and RTdose intensity . Ethics and dissemination The trial received ethical approval from NRES Committee North West — Greater Manchester Central ( 07/H1008/229 ) . There is a trial steering committee , including independent members and an independent data monitoring committee . Results will be published in a peer- review ed journal and presented at international conferences . Trial registration number IS RCT N91927162 ; Pre- results Background : Erlotinib ( Tarceva , OSI Pharmaceuticals , Melville , NY ) is an oral , epidermal growth factor receptor tyrosine kinase inhibitor that has antitumor activity and good tolerability in non-small cell lung cancer ( NSCLC ) . In particular , higher response rates have been reported in Asian patients than in Western patients . The aim of this study conducted by the Korean Cancer Study Group was to evaluate the efficacy and tolerability of erlotinib monotherapy as a palliative treatment for advanced NSCLC patients in Korea . Patients and Methods : Patients with histologically or cytologically confirmed stage IIIB or IV NSCLC including recurrent or metastatic disease , with performance status from 0 to 3 , were eligible either if they had received any anticancer treatment except epidermal growth factor receptor inhibitors or if they were unsuitable for chemotherapy because of poor performance status . Enrolled patients were treated with oral erlotinib at a dose of 150 mg daily until disease progression or development of intolerable toxicity . Results : A total of 120 patients were enrolled between January 2005 and May 2006 . Forty-four patients ( 36.7 % ) were female and 72 patients were current or former smoker . Fifty percent of patients had received one prior palliative chemotherapy regimens and 34.2 % had two or more prior palliative regimens . The overall tumor response rate was 24.2 % ( 95 % confidence interval [ CI ] , 16.8–32.8 % ) with 4 complete responses and 25 partial responses , and the disease control rate was 56.7 % . The favorable clinical variables for tumor response were female ( P = 0.001 ) , never smokers ( P = 0.041 ) , and adenocarcinoma ( P = 0.001 ) . The most common adverse event was skin rash ( 78 % of which grade 3 or 4 skin rash occurred in 13.3 % of the patients ) . With a median follow-up of 23.6 months , the median time to progression was 2.7 months ( 95 % CI , 2.2–3.2 ) , and the median overall survival was 12.9 months ( 95 % CI , 6.9–18.8 ) . By multivariate analysis , female and development of skin rash were significantly associated with longer time to progression and overall survival . Conclusion : Erlotinib monotherapy showed significant antitumor activity and an acceptable tolerability profile as a palliative treatment in advanced NSCLC patients in Korea , especially in females , never smokers , and patients with adenocarcinoma histology OBJECTIVES The clinical benefit of chemotherapy and the appropriate regimen for non-small-cell lung cancer ( NSCLC ) patients with interstitial lung disease ( ILD ) remain unclear . To fulfill this unmet medical need , we conducted a phase II study to eluci date the efficacy of S-1 in combination with carboplatin ( CBDCA ) in NSCLC patients with ILD . MATERIAL S AND METHODS A total of 33 advanced or recurrent NSCLC patients with ILD were prospect ively enrolled in this multicenter , open-label , phase II study . Every 4 weeks , CBDCA at a dose of AUC 5 on day 1 and S-1 at a dose of 80 mg/m2 daily for 14 days were administered . The primary endpoint was the investigator-assessed objective response rate . RESULTS The median age at initiating chemotherapy was 70 . Sixteen patients ( 48.5 % ) had squamous cell carcinoma histology . With respect to the types of ILD , the usual interstitial pneumonia pattern was dominant ( 66.7 % ) . The median number of cycles administered was 3 , and the overall response rate and disease control rate were 33.3 % and 78.8 % , respectively . The median progression-free survival , the median survival time and the 1-year survival rate were 4.8 months , 12.8 months and 51.4 % , respectively . Acute exacerbation of ILD caused by chemotherapy was noted in 2 patients ( 6.1 % ) . CONCLUSION This is the first prospect i ve study design ed to evaluate the efficacy of a specific chemotherapeutic regimen as the primary endpoint in patients with advanced NSCLC with ILD . The combination of S-1 with CBDCA may be a treatment option for advanced NSCLC patients with ILD ( The clinical trial registration number : UMIN000011046 ) Abstract Background Chemotherapy remains a viable option for the management of advanced non-small-cell lung cancer ( NSCLC ) despite recent advances in molecular targeted therapy and immunotherapy . We evaluated the efficacy of oral 5-fluorouracil-based S-1 as second- or third-line therapy compared with st and ard docetaxel therapy in patients with advanced NSCLC . Patients and methods Patients with advanced NSCLC previously treated with ≥1 platinum-based therapy were r and omized 1 : 1 to docetaxel ( 60 mg/m2 in Japan , 75 mg/m2 at all other study sites ; day 1 in a 3-week cycle ) or S-1 ( 80–120 mg/day , depending on body surface area ; days 1–28 in a 6-week cycle ) . The primary endpoint was overall survival . The non-inferiority margin was a hazard ratio ( HR ) of 1.2 . Results A total of 1154 patients ( 577 in each arm ) were enrolled , with balanced patient characteristics between the two arms . Median overall survival was 12.75 and 12.52 months in the S-1 and docetaxel arms , respectively [ HR 0.945 ; 95 % confidence interval ( CI ) 0.833–1.073 ; P = 0.3818 ] . The upper limit of 95 % CI of HR fell below 1.2 , confirming non-inferiority of S-1 to docetaxel  . Difference in progression-free survival between treatments was not significant ( HR 1.033 ; 95 % CI 0.913–1.168 ; P = 0.6080 ) . Response rate was 8.3 % and 9.9 % in the S-1 and docetaxel arms , respectively . Significant improvement was observed in the EORTC QLQ-C30 global health status over time points in the S-1 arm . The most common adverse drug reactions were decreased appetite ( 50.4 % ) , nausea ( 36.4 % ) , and diarrhea ( 35.9 % ) in the S-1 arm , and neutropenia ( 54.8 % ) , leukocytopenia ( 43.9 % ) , and alopecia ( 46.6 % ) in the docetaxel arm . Conclusion S-1 is equally as efficacious as docetaxel and offers a treatment option for patients with previously treated advanced NSCLC . Clinical trial number Japan Pharmaceutical Information Center , JapicCTI-101155 BACKGROUND : According to the literature , performance status , stage-tumor dimension and nodal status , weight loss , were the most important prognostic factors for survival in patients with locally advanced non-small cell lung cancer . AIM : To evaluate the treatment results and the prognostic variables in our patients treated with sequential and concurrent chemoradiotherapy .  MATERIAL AND METHODS : In the study 85 patients were r and omly assigned to one of the two treatment arms . In the sequential arm , 45 patients had previously received  sequential chemotherapy with 4 cycles of and etoposide followed by conformal radiotherapy ( RT ) . In the second concurrent group , 40 patients received  concomitant chemotherapy of cisplatine and etoposide and conformal RT , followed by two cycles of consolidation chemotherapy of carboplatine and etoposide . We described all phases of the conformal three dimensional ( 3-D ) RT . RESULTS : From October 2005 to March 2008 , 93 patients were enrolled . Eight patients were not eligible , seven had stage IV and one patient had pleural effusion . They were all initially considered to have stage IIIB disease . The median survival was 13 months for the patients in the sequential arm and 19 months for those in the concurrent treatment arm . The differences were statistically significant ( log-rank test p=0.0039 ) . The disease-free survival was 9 months in the sequential arm and 16 months in the concurrent treatment group . The differences were statistically significant ( log-rank test p=0.0023 ) . We found that the following prognostic factors significantly influenced the survival in lung cancer patients treated with conservative method : - age , p<0.05 ; - performant status , p<0.001 ; - weight loss , p<0.001 ; tumor dimension , p<0.05 ; and - nodal involvement , p<0.05 . CONCLUSION : In our study , the dose-limiting toxicity , esophagitis was reduced by performing conformal radiotherapy . Conformal thoracic radiotherapy and new radiotherapy technics , such as respiratory gated radiotherapy , allow dose escalating and may probably improve survival and local control in lung cancer patients Purpose To provide evidence -based recommendations to up date the American Society of Clinical Oncology guideline on systemic therapy for stage IV non – small-cell lung cancer ( NSCLC ) . Methods An Up date Committee of the American Society of Clinical Oncology NSCLC Expert Panel based recommendations on a systematic review of r and omized controlled trials from January 2007 to February 2014 . Results This guideline up date reflects changes in evidence since the previous guideline . Recommendations There is no cure for patients with stage IV NSCLC . For patients with performance status ( PS ) 0 to 1 ( and appropriate patient cases with PS 2 ) and without an EGFR-sensitizing mutation or ALK gene rearrangement , combination cytotoxic chemotherapy is recommended , guided by histology , with early concurrent palliative care . Recommendations for patients in the first-line setting include platinum-doublet therapy for those with PS 0 to 1 ( bevacizumab may be added to carboplatin plus paclitaxel if no contraindications ) ; combination or single-agent chemotherapy or palliative care alone for those with PS 2 ; afatinib , erlotinib , or gefitinib for those with sensitizing EGFR mutations ; crizotinib for those with ALK or ROS1 gene rearrangement ; and following first-line recommendations or using platinum plus etoposide for those with large-cell neuroendocrine carcinoma . Maintenance therapy includes pemetrexed continuation for patients with stable disease or response to first-line pemetrexed-containing regimens , alternative chemotherapy , or a chemotherapy break . In the second-line setting , recommendations include docetaxel , erlotinib , gefitinib , or pemetrexed for patients with nonsquamous cell carcinoma ; docetaxel , erlotinib , or gefitinib for those with squamous cell carcinoma ; and chemotherapy or ceritinib for those with ALK rearrangement who experience progression after crizotinib . In the third-line setting , for patients who have not received erlotinib or gefitinib , treatment with erlotinib is recommended . There are insufficient data to recommend routine third-line cytotoxic therapy . Decisions regarding systemic therapy should not be made based on age alone . Additional information can be found at http://www.asco.org/ guidelines /nsclc and http://www.asco.org/ guidelines wiki . J Clin Oncol 33:3488 - 3515 . © 2015 by American Society of Clinical e18015 Background : Significant advances in the systemic management of metastatic non-small cell lung cancer ( NSCLC ) have occurred over the past decade , with options now including multiple lines of chemotherapy , EGFR inhibitors , and anti-angiogenic agents . Improvements in overall survival have been demonstrated in r and omized controlled trials comparing these newer agents to best supportive care ( BSC ) or st and ard therapy . This study examined uptake of these therapies in general practice and their impact on survival . METHODS This retrospective cohort study compared demographic , treatment and survival data among 987 patients diagnosed with stage IV NSCLC at two institutions in 1998 , 2003 , and 2008 . Cohorts were selected based on intervals when doublet chemotherapy , second line chemotherapy , and targeted agents were incorporated into the st and ard treatment regimen . RESULTS The proportion of patients receiving systemic therapy increased over time ( 20 % in 1998 , 42 % in 2008 ) . Treated patients diagnosed in 2008 were more likely to receive ≥2 lines of systemic therapy ( 60 % vs. 7 % in 1998 ) . Overall survival improved significantly across cohorts ( P < 0.001 ) , with 2 year survival rates of 0.3 % in 1998 , 4 % in 2003 , and 15 % in 2008 . After controlling for other variables , risk of death was diminished by 55 % in patients receiving 1 line of systemic therapy and 72 % in those receiving ≥2 lines , compared with BSC alone . Elderly patients ( age ≥70 years ) were also more likely to receive systemic therapy over time , with improved overall survival ( P < 0.001 ) . CONCLUSIONS Over the past decade , there has been increased use of systemic therapy in stage IV NSCLC patients , including the elderly . This has been associated with significantly improved overall survival PURPOSE This trial was conducted to determine the optimal duration of chemotherapy in Korean patients with advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Patients with stages IIIB to IV NSCLC who had not progressed after two cycles of chemotherapy were r and omly assigned to receive either four ( arm A ) or two ( arm B ) more cycles of third-generation , platinum-doublet treatment . RESULTS Of the 452 enrolled patients , 314 were r and omly assigned to the groups . One-year survival rates were 59.0 % in arm A and 62.4 % in arm B , and the difference of 3.4 % ( 95 % CI , -8.0 to 4.8 ) met the predefined criteria for noninferiority . The median time to progression ( TTP ) , however , was 6.2 months ( 95 % CI , 5.7 to 6.7 months ) in arm A and 4.6 months ( 95 % CI , 4.4 to 4.8 months ) in arm B , the difference of which is statistically significant ( P = .001 ) . The frequencies of hematologic and nonhematologic toxicities were similar in the two arms . CONCLUSION This study confirms the noninferiority of overall survival with four cycles compared with six cycles of chemotherapy for the first-line treatment of advanced NSCLC and supports the current American Society of Clinical Oncology guidelines . Notably , patients receiving six cycles of chemotherapy compared with four cycles showed a favorable TTP , suggesting that further investigation of the new strategies of maintenance therapy with less toxic agents after three to four cycles of induction chemotherapy might be warranted to improve survival , with consideration of both ethnicity and pharmacogenomic signatures Background Evidence that chemotherapy improves survival and quality of life in patients with stage IIIB & IV non small cell lung cancer ( NSCLC ) is based on large r and omized controlled trials . The purpose of this study was to determine eligibility of patients with advanced NSCLC for major chemotherapy trials . Methods Physicians treating stage IIIB/IV NSCLC at Sydney Cancer Centre assessed patient eligibility for the E1594 , SWOG9509 and TAX326 trials for patients presenting from October 2001 to December 2002 . A review of the centre 's registry was used to obtain missing data . Results 199 patients with advanced NSCLC were registered during the 14-month period . Characteristics of 100 patients were defined prospect ively , 85 retrospectively : 77 % males , median age 68 ( range 32–88 ) , 64 % stage IV disease . Only 35 % met trial eligibility for E1594 and 28 % for SWOG9509 and TAX326 . Common reasons for in eligibility were : co-morbidities 75(40 % ) ; ECOG Performance Status ≥2 72(39 % ) ; symptomatic brain metastasis 15(8 % ) ; and previous cancers 21(11 % ) . Many patients were ineligible by more than one criterion . Conclusion The majority of patients with advanced NSCLC were ineligible for the large chemotherapy trials . The applicability of trial results to advanced lung cancer population s may be limited . Future trials should be conducted in a more representative population Background Accelerated hypofractionated radiotherapy can shorten total treatment time and overcome the accelerated re population of tumour cells during radiotherapy . This therapeutic approach has demonstrated good efficacy in the treatment of locally advanced non-small-cell lung cancer ( NSCLC ) . However , the optimal fractionation scheme remains uncertain . The purpose of this phase I trial was to explore the maximum tolerated dose ( MTD ) of accelerated hypofractionated three-dimensional conformal radiotherapy ( 3-DCRT ) ( at 3 Gy/fraction ) administered in combination with concurrent vinorelbine ( NVB ) and carboplatin ( CBP ) chemotherapy for unresectable stage III NSCLC . Methods Previously untreated cases of unresectable stage III NSCLC received accelerated hypofractionated 3-DCRT , delivered at 3 Gy per fraction , once daily , with five fractions per week . The starting dose was 66 Gy and an increment of 3 Gy was utilized . Higher doses continued to be tested in patient groups until the emergence of dose-limiting toxicity ( DLT ) . The MTD was regarded as the dose that was one step below the dose at which DLT occurred . Patients received at least one cycle of a concurrent two-drug chemotherapy regimen of NVB and CBP . Results A total of 13 patients were enrolled and progressed through three dose escalation groups : 66 Gy , 69 Gy , and 72 Gy . No treatment-related deaths occurred . The major adverse events included radiation oesophagitis , radiation pneumonitis , and neutropenia . Nausea , fatigue , and anorexia were commonly observed , although the magnitude of these events was typically relatively minor . Among the entire group , four instances of DLT were observed , including two cases of grade 3 radiation oesophagitis , one case of grade 3 radiation pneumonitis , and one case of grade 4 neutropenia . All of these cases of DLT occurred in the 72 Gy group . Therefore , 72 Gy was design ated as the DLT dose level , and the lower dose of 69 Gy was regarded as the MTD . Conclusions For unresectable stage III NSCLC 69 Gy ( at 3 Gy/fraction ) was the MTD of accelerated hypofractionated 3-DCRT administered in combination with concurrent NVB and CBP chemotherapy . The toxicity of this chemoradiotherapy regimen could be tolerated . A phase II trial is recommended to further evaluate the efficacy and safety of this regimen Summary Objectives Unsatisfactory efficacy of current treatments for advanced lung cancer has prompted the search for new therapies , with sorafenib , a multikinase inhibitor , being one c and i date drug . This phase I trial was conducted to evaluate drug safety and pharmacokinetics as well as tumor response of sorafenib in combination with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer ( NSCLC ) . Methods Eligible patients received paclitaxel ( 200 mg/m2 ) and carboplatin ( area under the curve [AUC]of 6 mg min mL−1 ) on day 1 and sorafenib ( 400 mg , twice daily ) on days 2 through 19 of a 21-day cycle . Results Four of the initial six patients ( cohort 1 ) experienced dose-limiting toxicities ( DLTs ) , result ing in amendment of the treatment protocol . An additional seven patients ( cohort 2 ) were enrolled , two of whom developed DLTs . DLTs included erythema multiforme , h and -foot skin reaction , and elevated plasma alanine aminotransferase in cohort 1 as well as gastrointestinal perforation at a site of metastasis and pneumonia in cohort 2 . Most adverse events were manageable . One complete and six partial responses were observed among the 12 evaluable patients . Coadministration of the three drugs had no impact on their respective pharmacokinetics . Conclusion The present study confirmed that sorafenib at 400 mg once daily in combination with carboplatin AUC 5 mg min mL−1 and paclitaxel 200 mg/m2 is feasible in Japanese patients with advanced NSCLC . The results of this study also showed that this combination therapy had encouraging antitumor activity and was not associated with relevant pharmacokinetic interaction in Japanese NSCLC patients Summary Background Ipilimumab is an antibody that targets the cytotoxic T-lymphocyte antigen-4 to potentiate an antitumor response . Adding ipilimumab 10 mg/kg to paclitaxel ( PTX ) and carboplatin ( CBDCA ) in a phased schedule improved progression-free survival in a phase II non-small-cell lung cancer ( NSCLC ) study . Methods This dose-escalating , phase I study was design ed to identify the recommended dose of ipilimumab ( 3 or 10 mg/kg ) by evaluating dose-limiting toxicity ( DLT ; Cycles 3 and 4 ) in phased combination with PTX ( 175 mg/m2 ) and CBDCA ( area under the curve = 6 ) in Japanese patients with advanced NSCLC . Treatment was administered intravenously every 3 weeks initially , followed by some eligible patients receiving maintenance ipilimumab once every 12 weeks . Additional endpoints included safety , tumor response , pharmacokinetics , and immunogenicity . Results Fifteen patients were enrolled and 12 received ipilimumab ( n = 6 , 3 mg/kg ; n = 6 , 10 mg/kg ) in combination with PTX and CBDCA .  DLTs occurred in 2 patients ( ipilimumab 3 mg/kg ) and 1 patient ( ipilimumab 10 mg/kg ) . The most common grade 3/4 adverse events ( AEs ) were decreased hemoglobin , leukopenia , and neutropenia . The most common immune-related AEs affected the skin , gastrointestinal , and nervous system . The safety profile was similar in both cohorts . Three patients in each cohort achieved a partial response . The pharmacokinetic ( PK ) profile of ipilimumab in Japanese patients was similar to that observed in previous studies in non-Japanese patients . Conclusions The recommended dose of ipilimumab in phased combination with PTX and CBDCA in Japanese patients with NSCLC was identified as 10 mg/kg . The safety profile was consistent with the previously defined AE profile
We believe that this attempt enables clinicians to choose appropriate treatment easier .
According to rapid development of chemotherapy in advanced non-small cell lung cancer ( NSCLC ) , the Japan Lung Cancer Society has been up date d its own guideline annually since 2010 .
Recently , we have had various types of chemotherapeutic drugs like kinase inhibitors or immune-checkpoint inhibitors .
Thus , the guideline proposes to categorize patients into three entities : ( 1 ) driver oncogene-positive , ( 2 ) PD-L1 ≥ 50 % , and ( 3 ) others .
Here , we report an English version of the Japan Lung Cancer Society Guidelines 2018 for NSCLC , stages IV