title: Concomitant chemoradiation versus radical radiotherapy in advanced squamous cell carcinoma of oropharynx and nasopharynx using weekly cisplatin: a phase II randomized trial. Lack of Cumulative Toxicity Associated With Cabazitaxel Use in Prostate Cancer Feasibility study of docetaxel with cyclophosphamide as adjuvant chemotherapy for Japanese breast cancer patients. Randomised phase III study of neoadjuvant chemotherapy with methotrexate, doxorubicin, vinblastine and cisplatin followed by radical cystectomy compared with radical cystectomy alone for muscle-invasive bladder cancer: Japan Clinical Oncology Group Study JCOG0209. Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stage III colon cancer. Eligibility of patients with advanced non-small cell lung cancer for phase III chemotherapy trials Influence of comorbidities and age on risk of death without recurrence: a retrospective analysis of the Arimidex, Tamoxifen Alone or in Combination trial. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. Effect of age and comorbidity in postmenopausal breast cancer patients aged 55 years and older. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. Preoperative chemoradiotherapy for esophageal or junctional cancer. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. Epirubicin increases long-term survival in adjuvant chemotherapy of patients with poor-prognosis, node-positive, early breast cancer: 10-year follow-up results of the French Adjuvant Study Group 05 randomized trial. Dose and dose intensity as determinants of outcome in the adjuvant treatment of breast cancer. The Cancer and Leukemia Group B. Docetaxel and carboplatin is an active regimen in advanced non-small-cell lung cancer: a phase II study in Caucasian and Asian patients. Induction chemotherapy with docetaxel, cisplatin, fluorouracil and l-leucovorin for locally advanced head and neck cancers: a modified regimen for Japanese patients Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. Outcomes and toxicity in african-american and caucasian patients in a randomized adjuvant chemotherapy trial for colon cancer. Phase III study of cisplatin, etoposide, and concurrent chest radiation with or without consolidation docetaxel in patients with inoperable stage III non-small-cell lung cancer: the Hoosier Oncology Group and U.S. Oncology. Capecitabine as adjuvant treatment for stage III colon cancer. Relationship between toxicity and obesity in women receiving adjuvant chemotherapy for breast cancer: results from cancer and leukemia group B study 8541. Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2 × 2 factorial trial. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. Chemoradiation comparing cisplatin versus carboplatin in locally advanced nasopharyngeal cancer: randomised, non-inferiority, open trial. Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) as neoadjuvant chemotherapy for patients with muscle‐invasive transitional cell carcinoma of the bladder
abstract: BACKGROUND To know the effectiveness and tolerance of weekly cisplatin added to radiotherapy ( RT ) in advanced carcinoma of oropharynx and nasopharynx . PATIENTS AND METHODS Stage II-IV cancer patients were r and omly assigned to either radical RT , 70 Gy/35 fractions over 7 weeks ( RT arm ) , or chemoradiotherapy ( CRT ) , cisplatin 40 mg/m² weekly for seven doses plus RT . Primary end points were ( i ) the responses , ( ii ) toxicity profile , and ( iii ) overall survival ( OS ) in two groups . Study period was from June 2003 to July 2005 . RESULTS One hundred and fifty-three patients were r and omly allocated to the study , 76 in RT arm and 77 in CRT arm . Seventy-one in each arm completed the planned treatment ; complete response ( CR ) : 67.1 % versus 80.5 % in RT and CRT arms ( P = 0.04 ) . Grade III and IV toxicity were 16 % and 40 % in RT and CRT arms , respectively ( P = 0.01 ) . There were frequent treatment interruptions ( 9.3 % versus 28.9 % ; P = 0.003 ) and hospitalization ( 20 % versus 40.8 % ) in the CRT group . OS was superior in the CRT arm ( P = 0.02 ) : 27 months [ 95 % confidence interval ( CI ) 15.2 - 36.8 ] for RT versus not reached for CRT . Three-year OS was 42 % for RT and 62 % for CRT group . CRT and CR were independent prognostic factors . CONCLUSION This trial on Indian head and neck squamous cell carcinoma patients confirms that the use of weekly cisplatin is safe and CRT is superior to RT alone result ing in higher OS Abstract Cabazitaxel provided a survival advantage compared with mitoxantrone in patients with castration-resistant prostate cancer refractory to docetaxel .  Grade 3 to 4 ( G3–4 ) neutropenia and febrile neutropenia were relatively frequent in the registrative XRP6258 Plus Prednisone Compared to Mitoxantrone Plus Prednisone in Hormone Refractory Metastatic Prostate Cancer ( TROPIC ) trial , but their incidence was lower in the Exp and ed Access Program ( EAP ) . Although cumulative doses of docetaxel are associated with neuropathy , the effect of cumulative doses of cabazitaxel is unknown . In this retrospective review of prospect ively collected data , the authors assessed “ per cycle ” incidence and predictors of toxicity in the Italian cohort of the EAP , with a focus on the effect of cumulative doses of cabazitaxel . The study population consisted of 218 Italian patients enrolled in the cabazitaxel EAP . The influence of selected variables on the most relevant adverse events identified was assessed using a Generalized Estimating Equations model at univariate and multivariate analysis .“Per cycle ” incidence of G 3 to 4 neutropenia was 8.7 % , whereas febrile neutropenia was reported in 0.9 % of cycles . All events of febrile neutropenia occurred during the first 3 cycles . Multivariate logistic regression analysis showed that higher prior dose of cabazitaxel was associated with decreased odds of having G3 to 4 neutropenia ( OR = 0.90 ; 95 % CI : 0.86–0.93 ; P < 0.01 ) , febrile neutropenia ( OR = 0.52 ; 95 % CI : 0.34–0.81 ; P < 0.01 ) and G3 to 4 anemia ( OR = 0.93 ; 95 % CI : 0.86–1 ; P = 0.07 ) . Patients with a body surface area > 2 m2 presented increased odds of having G 3 to 4 neutropenia ( OR = 0.93 ; 95 % CI : 0.86–1 ; P = 0.07 ) , but decreased odds of having G3 to 4 anemia . Among the toxicities assessed , the authors did not identify any that appeared to be associated with a higher number of cabazitaxel cycles delivered . Prior cumulative dose was associated with reduced G3 to 4 neutropenia and anemia . The apparent protective effect associated with higher doses of cabazitaxel is likely to be affected by early dose reduction and early toxicity-related treatment discontinuation . Because this analysis is limited by its retrospective design , prospect i ve trials are required to assess the optimal duration of cabazitaxel treatment OBJECTIVE The 7-year follow-up of the US oncology 9735 trial demonstrated the superiority of TC [ docetaxel (DTX)/cyclophosphamide ( CPA ) ] to doxorubicin/CPA therapy . To introduce TC therapy in Japan , the verification of the safety and tolerability is essential . We performed a collaborative prospect i ve safety study with Okayama University to introduce TC therapy . METHODS The subjects were 53 patients aged from 33 to 67 years at intermediate risk based on the St Gallen risk classification who underwent radical surgery for primary breast cancer between August 2007 and December 2008 . As post-operative adjuvant chemotherapy , four cycles of TC ( DTX 75 mg/m(2 ) + CPA 600 mg/m(2 ) ) were administered at 3-week intervals . Adverse events were evaluated based on National Cancer Institute-Common Terminology Criteria for Adverse Events ver . 3.0 . The safety and completion rate were evaluated as the primary and secondary endpoints , respectively . RESULTS Regarding hematological toxicity , Grade ( G ) 4 neutropenia occurred in 71.7 % and G3 in 26.4 % . G3 - 4 leukopenia developed in 32.1 % and 56.6 % , respectively , G4 anemia in 1.9 % and G1 - 2 anemia in 26.4 % . Regarding non-hematological toxicity , systemic malaise , skin eruption , edema , myalgia , arthralgia and nausea were noted in most patients . The completion rate was 94.3 % , dose reduction was necessary in 7.5 % and granulocyte colony-stimulating factor ( G-CSF ) support was required in 17.0 % . On comparison between patients aged 65 years or older and younger than 65 years , the completion rate , dose reduction and incidence of febrile neutropenia ( FN ) were higher in the elderly patients . G-CSF support was more often needed in this subgroup . CONCLUSIONS TC therapy is tolerable for Japanese patients , but attention should be paid to the development of FN and neutropenia . The completion rate was lower in the elderly patients , showing that tolerability was not necessarily favorable BACKGROUND This study aim ed to determine the clinical benefit of neoadjuvant methotrexate , doxorubicin , vinblastine , and cisplatin ( MVAC ) in patients with muscle-invasive bladder cancer ( MIBC ) treated with radical cystectomy . PATIENTS AND METHODS Patients with MIBC ( T2 - 4aN0M0 ) were r and omised to receive two cycles of neoadjuvant MVAC followed by radical cystectomy ( NAC arm ) or radical cystectomy alone ( RC arm ) . The primary end point was overall survival ( OS ) . Secondary end points were progression-free survival , surgery-related complications , adverse events during chemotherapy , proportion with no residual tumour in the cystectomy specimens , and quality of life . To detect an improvement in 5-year OS from 45 % in the RC arm to 57 % in the NAC arm with 80 % power , 176 events were required per arm . RESULTS Patients ( N = 130 ) were r and omly assigned to the RC arm ( N = 66 ) and the NAC arm ( N = 64 ) . The patient registration was terminated before reaching the initially planned number of patients because of slow accrual . At the second interim analysis just after the early stoppage of patient accrual , the Data and Safety Monitoring Committee recommended early publication of the results because the trial did not have enough power to draw a confirmatory conclusion . OS of the NAC arm was better than that of the RC arm , although the difference was not statistically significant [ hazard ratio 0.65 , multiplicity adjusted 99.99 % confidence interval 0.19 - 2.18 , one-sided P = 0.07 ] . In the NAC arm and the RC arm , 34 % and 9 % of the patients had pT0 , respectively ( P < 0.01 ) . In subgroup analyses , OS in almost all subgroups was in favour of NAC . CONCLUSIONS This trial showed a significantly increased pT0 proportion and favourable OS of patients who received neoadjuvant MVAC . NAC with MVAC can still be considered promising as a st and ard treatment . UMIN CLINICAL TRIALS REGISTRY IDENTIFIER C000000093 PURPOSE This multicenter , r and omized trial compared capecitabine plus oxaliplatin ( XELOX ) with bolus fluorouracil ( FU ) and folinic acid ( FA ) as adjuvant therapy for patients with stage III colon cancer . PATIENTS AND METHODS Patients who had undergone curative resection were r and omly assigned to XELOX ( oxaliplatin 130 mg/m(2 ) on day 1 plus capecitabine 1,000 mg/m(2 ) twice daily on days 1 to 14 every 3 weeks for 24 weeks ) or a st and ard bolus FU/FA adjuvant regimen ( Mayo Clinic for 24 weeks or Roswell Park for 32 weeks ) . The primary study end point was disease-free survival ( DFS ) . RESULTS The intention-to-treat population comprised 1,886 patients ; 944 patients were r and omly assigned to XELOX and 942 to FU/FA ( Mayo Clinic , n = 664 ; Roswell Park , n = 278 ) . After 57 months of follow-up for the primary analysis , 295 patients ( 31.3 % ) in the XELOX group had relapsed , developed a new primary colon cancer , or died compared with 353 patients ( 37.5 % ) in the FU/FA group ( hazard ratio [ HR ] for DFS , 0.80 ; 95 % CI , 0.69 to 0.93 ; P = .0045 ) . The 3-year DFS rate was 70.9 % with XELOX and 66.5 % with FU/FA . The HR for overall survival ( OS ) for XELOX compared to FU/FA was 0.87 ( 95 % CI , 0.72 to 1.05 ; P = .1486 ) . The 5-year OS for XELOX and FU/FA were 77.6 % and 74.2 % , respectively . Follow-up is ongoing . Preplanned multivariate and subgroup analyses supported the robustness of these findings . CONCLUSION The addition of oxaliplatin to capecitabine improves DFS in patients with stage III colon cancer . XELOX is an additional adjuvant treatment option for these patients 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 PURPOSE The Arimidex , Tamoxifen Alone or in Combination ( ATAC ) study was a double-blind r and omized trial in which postmenopausal women with early-stage breast cancer were assigned to receive anastrozole , tamoxifen , or the combination . We have conducted a retrospective analysis to examine the effects of comorbidities and age on treatment received , breast cancer-related mortality , and competing causes of mortality . PATIENTS AND METHODS The current analyses were based on 10-year median follow-up data in the two monotherapy arms ( anastrozole  , n = 3,092  ; tamoxifen  , n = 3,094 ) of the ATAC study . Baseline comorbidities and tumor and treatment characteristics were compared between women age less than 70 years and women age ≥ 70 years . The cumulative incidence of breast cancer-related and non-breast cancer-related mortality was assessed according to age and comorbidities . RESULTS One thous and six hundred sixty-two patients ( 27 % ) were age ≥ 70 years at study entry . Older women were more likely to undergo mastectomy ( odds ratio [ OR ] , 1.92 ; 95 % CI , 1.71 to 2.16 ) and less likely to receive radiotherapy ( OR , 0.49 ; 95 % CI , 0.44 to 0.55 ) or chemotherapy ( OR , 0.24 ; 95 % CI , 0.18 to 0.29 ) . Women age ≥ 70 years had an increased risk of recurrence compared with women age less than 70 years ( hazard ratio [ HR ] , 1.21 ; 95 % CI , 1.08 to 1.37 ) and a substantially increased risk of death without recurrence ( HR , 4.13 ; 95 % CI , 3.53 to 4.83 ) . The risk of death without recurrence increased with comorbidity score ( 10-year estimates of 8.4 % , 20.0 % , and 30.4 % for Satariano score 0 , 1 , and 2 + , respectively ; P < .001 ) . CONCLUSION Age influences the risk of recurrence , and age and comorbidities significantly influence the risk of death without recurrence . Formal assessment of comorbidities should be incorporated into decisions regarding adjuvant therapies CONTEXT Adjuvant fluorouracil has been shown to be of benefit for patients with resected pancreatic cancer .  Gemcitabine is known to be the most effective agent in advanced disease as well as an effective agent in patients with resected pancreatic cancer . OBJECTIVE To determine whether fluorouracil or gemcitabine is superior in terms of overall survival as adjuvant treatment following resection of pancreatic cancer . DESIGN , SETTING , AND PATIENTS The European Study Group for Pancreatic Cancer (ESPAC)-3 trial , an open-label , phase 3 , r and omized controlled trial conducted in 159 pancreatic cancer centers in Europe , Australasia , Japan , and Canada . Included in ESPAC-3 version 2 were 1088 patients with pancreatic ductal adenocarcinoma who had undergone cancer resection ; patients were r and omized between July 2000 and January 2007 and underwent at least 2 years of follow-up . INTERVENTIONS Patients received either fluorouracil plus folinic acid ( folinic acid , 20 mg/m(2 ) , intravenous bolus injection , followed by fluorouracil , 425 mg/m(2 ) intravenous bolus injection given 1 - 5 days every 28 days ) ( n = 551 ) or gemcitabine ( 1000 mg/m(2 ) intravenous infusion once a week for 3 of every 4 weeks ) ( n = 537 ) for 6 months . MAIN OUTCOME MEASURES Primary outcome measure was overall survival ; secondary measures were toxicity , progression-free survival , and quality of life . RESULTS Final analysis was carried out on an intention-to-treat basis after a median of 34.2 ( interquartile range , 27.1 - 43.4 ) months ' follow-up after 753 deaths ( 69 % ) . Median survival was 23.0 ( 95 % confidence interval [ CI ] , 21.1 - 25.0 ) months for patients treated with fluorouracil plus folinic acid and 23.6 ( 95 % CI , 21.4 - 26.4 ) months for those treated with gemcitabine ( chi(1)(2 ) = 0.7 ; P = .39 ; hazard ratio , 0.94 [ 95 % CI , 0.81 - 1.08 ] ) . Seventy-seven patients ( 14 % ) receiving fluorouracil plus folinic acid had 97 treatment-related serious adverse events , compared with 40 patients ( 7.5 % ) receiving gemcitabine , who had 52 events ( P < .001 ) . There were no significant differences in either progression-free survival or global quality -of-life scores between the treatment groups . CONCLUSION Compared with the use of fluorouracil plus folinic acid , gemcitabine did not result in improved overall survival in patients with completely resected pancreatic cancer . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00058201 BACKGROUND Whether adjuvant chemotherapy improves survival of patients with non-small-cell lung cancer ( NSCLC ) is not known . We aim ed to compare the effect of adjuvant vinorelbine plus cisplatin versus observation on survival in patients with completely resected NSCLC . METHODS 840 patients with stage IB-IIIA NSCLC from 101 centres in 14 countries were r and omly assigned to observation ( n=433 ) or to 30 mg/m(2 ) vinorelbine plus 100 mg/m(2 ) cisplatin ( n=407 ) . Postoperative radiotherapy was not m and atory and was undertaken according to every centre 's policy . The primary endpoint was overall survival . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N95053737 . FINDINGS 367 patients in the chemotherapy group and 431 in the control group received their assigned treatment . 301 ( 36 % ) patients had stage IB disease , 203 ( 24 % ) had stage II disease , and 325 ( 39 % ) had stage IIIA disease . Tolerance to chemotherapy mainly included neutropenia in 335 ( 92 % ) patients and febrile neutropenia in 34 ( 9 % ) ; seven ( 2 % ) toxic deaths were also recorded . Compliance was greater with cisplatin than with vinorelbine ( median dose intensity 89 % [ range 17 - 108 ] vs 59 % [ 17 - 100 ] ) . After a median follow-up of 76 months ( range 43 - 116 ) , median survival was 65.7 months ( 95 % CI 47.9 - 88.5 ) in the chemotherapy group and 43.7 ( 35.7 - 52.3 ) months in the observation group . Adjusted risk for death was significantly reduced in patients assigned chemotherapy compared with controls ( hazard ratio 0.80 [ 95 % CI 0.66 - 0.96 ] ; p=0.017 ) . Overall survival at 5 years with chemotherapy improved by 8.6 % , which was maintained at 7 years ( 8.4 % ) . INTERPRETATION Adjuvant vinorelbine plus cisplatin extends survival in patients with completely resected NSCLC , better defining indication of adjuvant chemotherapy BACKGROUND We conducted a multinational , r and omized study to compare radiotherapy alone with radiotherapy plus cetuximab , a monoclonal antibody against the epidermal growth factor receptor , in the treatment of locoregionally advanced squamous-cell carcinoma of the head and neck . METHODS Patients with locoregionally advanced head and neck cancer were r and omly assigned to treatment with high-dose radiotherapy alone ( 213 patients ) or high-dose radiotherapy plus weekly cetuximab  ( 211 patients ) at an initial dose of 400 mg per square meter of body-surface area , followed by 250 mg per square meter weekly for the duration of radiotherapy . The primary end point was the duration of control of locoregional disease ; secondary end points were overall survival , progression-free survival , the response rate , and safety . RESULTS The median duration of locoregional control was 24.4 months among patients treated with cetuximab plus radiotherapy and 14.9 months among those given radiotherapy alone ( hazard ratio for locoregional progression or death , 0.68 ; P=0.005 ) . With a median follow-up of 54.0 months , the median duration of overall survival was 49.0 months among patients treated with combined therapy and 29.3 months among those treated with radiotherapy alone ( hazard ratio for death , 0.74 ; P=0.03 ) . Radiotherapy plus cetuximab significantly prolonged progression-free survival ( hazard ratio for disease progression or death , 0.70 ; P=0.006 ) . With the exception of acneiform rash and infusion reactions , the incidence of grade 3 or greater toxic effects , including mucositis , did not differ significantly between the two groups . CONCLUSIONS Treatment of locoregionally advanced head and neck cancer with concomitant high-dose radiotherapy plus cetuximab improves locoregional control and reduces mortality without increasing the common toxic effects associated with radiotherapy to the head and neck . ( Clinical Trials.gov number , NCT00004227 . CONTEXT Postmenopausal women aged 55 years and older have 66 % of incident breast tumors and experience 77 % of breast cancer mortality , but other age-related health problems may affect tumor prognosis and treatment decisions . OBJECTIVE To document the comorbidity burden of postmenopausal breast cancer patients and evaluate its relationship with age on disease stage , treatment , and early mortality . DESIGN AND SETTING Data were collected on breast cancer patients ' comorbidities by retrospective hospital medical records review and merged with information on patients ' tumor characteristics collected from 6 regional National Cancer Institute Surveillance , Epidemiology , and End Results cancer registries . Patients were followed up until death or for 30 months from breast cancer diagnosis . PARTICIPANTS Population -based r and om sample of 1800 postmenopausal breast cancer patients diagnosed in 1992 stratified by 3 age groups : 55 to 64 years , 65 to 74 years , and 75 years and older . MAIN OUTCOME MEASURES Extent of disease , therapy received , comorbidity , cause of death , and survival . RESULTS Seventy-three percent ( 1312 of 1800 ) of the sample was diagnosed with stage I and II breast cancer , 10 % ( n = 188 ) with stage III and IV breast cancer , and 17 % ( n = 300 ) did not have a stage assignment . Of the 1017 patients with stage I and stage II node-negative breast cancer , 95 % received therapy in agreement with the National Institutes of Health consensus statement recommendation for early-stage breast cancer . Patients in older age groups were less likely to receive therapy consistent with the consensus statement ( P<.001 ) , and women aged 70 years and older were significantly less likely to receive axillary lymph node dissection as determined by logistic regression analysis ( P<.01 ) . Diabetes , renal failure , stroke , liver disease , a previous malignant tumor , and smoking were significant in predicting early mortality in a statistical model that included age and disease stage . Breast cancer was the underlying cause of death for 135 decedents ( 51.3 % ) . Heart disease ( n = 45 , 17.1 % ) and previous cancers ( n = 22 , 8.4 % ) were the next major underlying causes . In the 30-month follow-up period , 263 patients ( 15 % ) died . CONCLUSION Patient care decisions occur in the context of breast cancer and other age-related conditions . Comorbidity in older patients may limit the ability to obtain prognostic information ( ie , axillary lymph node dissection ) , tends to minimize treatment options ( eg , breast-conserving therapy ) , and increases the risk of death from causes other than breast cancer CONTEXT The role of adjuvant therapy in resectable pancreatic cancer is still uncertain , and no recommended st and ard exists . OBJECTIVE To test the hypothesis that adjuvant chemotherapy with gemcitabine administered after complete resection of pancreatic cancer improves disease-free survival by 6 months or more . DESIGN , SETTING , AND PATIENTS Open , multicenter , r and omized controlled phase 3 trial with stratification for resection , tumor , and node status . Conducted from July 1998 to December 2004 in the outpatient setting at 88 academic and community-based oncology centers in Germany and Austria . A total of 368 patients with gross complete ( R0 or R1 ) resection of pancreatic cancer and no prior radiation or chemotherapy were enrolled into 2 groups . INTERVENTION Patients received adjuvant chemotherapy with 6 cycles of gemcitabine on days 1 , 8 , and 15 every 4 weeks ( n = 179 ) , or observation ( [ control ] n = 175 ) . MAIN OUTCOME MEASURES Primary end point was disease-free survival , and secondary end points were overall survival , toxicity , and quality of life . Survival analysis was based on all eligible patients ( intention-to-treat ) . RESULTS More than 80 % of patients had R0 resection . The median number of chemotherapy cycles in the gemcitabine group was 6 ( range , 0 - 6 ) . Grade 3 or 4 toxicities rarely occurred with no difference in quality of life ( by Spitzer index ) between groups . During median follow-up of 53 months , 133 patients ( 74 % ) in the gemcitabine group and 161 patients ( 92 % ) in the control group developed recurrent disease . Median disease-free survival was 13.4 months in the gemcitabine group ( 95 % confidence interval , 11.4 - 15.3 ) and 6.9 months in the control group ( 95 % confidence interval , 6.1 - 7.8 ; P<.001 , log-rank ) . Estimated disease-free survival at 3 and 5 years was 23.5 % and 16.5 % in the gemcitabine group , and 7.5 % and 5.5 % in the control group , respectively . Subgroup analyses showed that the effect of gemcitabine on disease-free survival was significant in patients with either R0 or R1 resection . There was no difference in overall survival between the gemcitabine group ( median , 22.1 months ; 95 % confidence interval , 18.4 - 25.8 ; estimated survival , 34 % at 3 years and 22.5 % at 5 years ) and the control group ( median , 20.2 months ; 95 % confidence interval , 17 - 23.4 ; estimated survival , 20.5 % at 3 years and 11.5 % at 5 years ; P = .06 , log-rank ) . CONCLUSIONS Postoperative gemcitabine significantly delayed the development of recurrent disease after complete resection of pancreatic cancer compared with observation alone . These results support the use of gemcitabine as adjuvant chemotherapy in resectable carcinoma of the pancreas . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N34802808 BACKGROUND The role of neoadjuvant chemoradiotherapy in the treatment of patients with esophageal or esophagogastric-junction cancer is not well established . We compared chemoradiotherapy followed by surgery with surgery alone in this patient population . METHODS We r and omly assigned patients with resectable tumors to receive surgery alone or weekly administration of carboplatin ( doses titrated to achieve an area under the curve of 2 mg per milliliter per minute ) and paclitaxel ( 50 mg per square meter of body-surface area ) for 5 weeks and concurrent radiotherapy ( 41.4 Gy in 23 fractions , 5 days per week ) , followed by surgery . RESULTS From March 2004 through December 2008 , we enrolled 368 patients , 366 of whom were included in the analysis : 275 ( 75 % ) had adenocarcinoma , 84 ( 23 % ) had squamous-cell carcinoma , and 7 ( 2 % ) had large-cell undifferentiated carcinoma . Of the 366 patients , 178 were r and omly assigned to chemoradiotherapy followed by surgery  , and 188 to surgery alone . The most common major hematologic toxic effects in the chemoradiotherapy-surgery group were leukopenia ( 6 % ) and neutropenia ( 2 % ) ; the most common major nonhematologic toxic effects were anorexia ( 5 % ) and fatigue ( 3 % ) . Complete resection with no tumor within 1 mm of the resection margins ( R0 ) was achieved in 92 % of patients in the chemoradiotherapy-surgery group versus 69 % in the surgery group ( P<0.001 ) . A pathological complete response was achieved in 47 of 161 patients ( 29 % ) who underwent resection after chemoradiotherapy . Postoperative complications were similar in the two treatment groups , and in-hospital mortality was 4 % in both . Median overall survival was 49.4 months in the chemoradiotherapy-surgery group versus 24.0 months in the surgery group . Overall survival was significantly better in the chemoradiotherapy-surgery group ( hazard ratio , 0.657 ; 95 % confidence interval , 0.495 to 0.871 ; P=0.003 ) . CONCLUSIONS Preoperative chemoradiotherapy improved survival among patients with potentially curable esophageal or esophagogastric-junction cancer . The regimen was associated with acceptable adverse-event rates . ( Funded by the Dutch Cancer Foundation [ KWF Kankerbestrijding ] ; Netherl and s Trial Register number , NTR487 . ) BACKGROUND The st and ard adjuvant treatment of colon cancer is fluorouracil plus leucovorin ( FL ) . Oxaliplatin improves the efficacy of this combination in patients with metastatic colorectal cancer . We evaluated the efficacy of treatment with FL plus oxaliplatin in the postoperative adjuvant setting . METHODS We r and omly assigned 2246 patients who had undergone curative resection for stage II or III colon cancer to receive FL alone or with oxaliplatin for six months . The primary end point was disease-free survival . RESULTS A total of 1123 patients were r and omly assigned to each group . After a median follow-up of 37.9 months , 237 patients in the group given FL plus oxaliplatin had had a cancer-related event , as compared with 293 patients in the FL group ( 21.1 percent vs. 26.1 percent ; hazard ratio for recurrence , 0.77 ; P=0.002 ) . The rate of disease-free survival at three years was 78.2 percent ( 95 percent confidence interval , 75.6 to 80.7 ) in the group given FL plus oxaliplatin and 72.9 percent ( 95 percent confidence interval , 70.2 to 75.7 ) in the FL group ( P=0.002 by the stratified log-rank test ) . In the group given FL plus oxaliplatin , the incidence of febrile neutropenia was 1.8 percent , the incidence of gastrointestinal adverse effects was low , and the incidence of grade 3 sensory neuropathy was 12.4 percent during treatment , decreasing to 1.1 percent at one year of follow-up . Six patients in each group died during treatment ( death rate , 0.5 percent ) . CONCLUSIONS Adding oxaliplatin to a regimen of fluorouracil and leucovorin improves the adjuvant treatment of colon cancer PURPOSE The French Adjuvant Study Group 05 ( FASG-05 ) showed that fluorouracil 500 mg/m2 , cyclophosphamide 500 mg/m2 , and epirubicin 100 mg/m2 ( FEC 100 ) was superior to the same regimen with epirubicin 50 mg/m2 ( FEC 50 ) in terms of disease-free survival ( DFS ) and overall survival ( OS ) in adjuvant treatment of early breast cancer . We report 10-year data on efficacy , and long-term side effects for FASG-05 . PATIENTS AND METHODS We r and omly assigned 565 patients to treatment with FEC 50 or FEC 100 after surgery . Postmenopausal patients also received tamoxifen for 3 years , and almost all patients ( 96 % ) also received radiotherapy . RESULTS Median follow-up was 110 months . The 10-year DFS was 45.3 % ( 95 % CI , 41.9 % to 48.7 % ) with FEC 50 and 50.7 % ( 95 % CI , 47.3 % to 54.1 % ) with FEC 100 ( Wilcoxon P = .036 ; log-rank P = .08 ) . The 10-year OS was 50.0 % ( 95 % CI , 46.7 % to 53.3 % ) with FEC 50 and 54.8 % ( 95 % CI , 51.3 % to 58.3 % ) with FEC 100 ( Wilcoxon P = .038 ; log-rank P = .05 ) . Delayed cardiac toxicity ( before relapse ) occurred in four patients ( 1.5 % ) in the FEC 50 arm and three patients ( 1.1 % ) in the FEC 100 arm . Cardiac toxicity after relapse occurred in six ( 4.3 % ) and five ( 4.1 % ) patients treated with FEC 50 and FEC 100 , respectively . CONCLUSION Treatment with adjuvant FEC 100 demonstrated superior DFS and OS versus FEC 50 at 10 years of follow-up . This survival advantage was not offset by long-term complications such as cardiac toxicity and second malignancy . Given the risk-benefit ratio , FEC 100 is a more optimal regimen for long-term survival in patients with poor prognosis BACKGROUND Both total dose and dose intensity of adjuvant chemotherapy are postulated to be important variables in the outcome for patients with operable breast cancer . The Cancer and Leukemia Group B study 8541 examined the effects of adjuvant treatment using conventional-range dose and dose intensity in female patients with stage II ( axillary lymph node-positive ) breast cancer . METHODS Within 6 weeks of surgery ( radical mastectomy , modified radical mastectomy , or lumpectomy ) , 1550 patients with unilateral breast cancer were r and omly assigned to one of three treatment arms : high- , moderate- , or low-dose intensity . The patients received cyclophosphamide , doxorubicin , and 5-fluorouracil on day 1 of each chemotherapy cycle , with 5-fluorouracil administration repeated on day 8 . The high-dose arm had twice the dose intensity and twice the drug dose as the low-dose arm . The moderate-dose arm had two thirds the dose intensity as the high-dose arm but the same total drug dose . Disease-free survival and overall survival were primary end points of the study . RESULTS At a median follow-up of 9 years , disease-free survival and overall survival for patients on the moderate- and high-dose arms are superior to the corresponding survival measures for patients on the low-dose arm ( two-sided P<.0001 and two-sided P = .004 , respectively ) , with no difference in disease-free or overall survival between the moderate- and the high-dose arms . At 5 years , overall survival ( average + /- st and ard error ) is 79 % + /- 2 % for patients on the high-dose arm , 77 % + /- 2 % for the patients on the moderate-dose arm , and 72 % + /- 2 % for patients on the low-dose arm ; disease-free survival is 66 % + /- 2 % , 61 % + /- 2 % , and 56 % + /- 2 % , respectively . CONCLUSION Within the conventional dose range for this chemotherapy regimen , a higher dose is associated with better disease-free survival and overall survival BACKGROUND The purpose of this study was to report response rates , survival and toxicity in advanced non-small-cell lung cancer ( NSCLC ) following docetaxel and carboplatin , and to explore potential differences in these end points between Caucasian and Asian patients . PATIENTS AND METHODS Sixty-eight patients of good performance status with Stage IIIB or IV NSCLC were entered on a phase II study at three sites in Australia and Singapore .  Docetaxel 75 mg/m2 and carboplatin AUC 6 were given every 3 weeks . Response to treatment and toxicity were grade d by st and ard criteria . The Kaplan-Meier method was used to estimate survival rates , and subgroups compared by the log-rank test . Cox 's proportional hazards regression was used to determine which potentially explanatory variables independently affected the outcome . RESULTS The response rate was 39 % ( 95 % confidence interval 27 % to 52 % ) , and 42 % in evaluable patients . Response occurred in 65 % of Asian and 31 % of Caucasian patients ( P = 0.01 ) . Ethnicity was the only significant predictor of response in multivariate analysis . The 1-year survival rate was 53 % . Performance status ( P = 0.021 ) , ethnicity ( P = 0.035 ) and presence of bone or liver metastases ( P = 0.011 ) were independent predictors of overall survival . Neutropenia ( grade IV in 73 % of patients ) , febrile neutropenia ( 26 % patients ) and diarrhea ( grade III/IV in 11 % of patients ) were the major treatment related toxicities . A high rate ( three of six ) of febrile neutropenia in Singapore , including one treatment-related death in the initial patients treated , result ed in a reduction in the carboplatin dose to AUC 4.5 at that site . CONCLUSIONS This regimen is active in advanced NSCLC . The potential impact of ethnicity on efficacy and toxicity of treatment requires further investigation Combination chemotherapy with docetaxel ( T ) , cisplatin ( P ) , fluorouracil ( 5-FU ) and leucovorin has been reported to have major activity against squamous cell carcinoma of the head and neck ( SCCHN ) administered as a 4-day ( TPFL4 ) or 5-day ( TPFL5 ) regimen . The purpose of this study was to evaluate the efficacy and toxicity of a modified TPFL regimen ( m-TPFL ) for locally advanced SCCHN , consisting of a modified dosage with docetaxel , cisplatin , 5-FU and l-leucovorin ( l-LV ) design ed for Japanese patients . Organ preservation of the primary tumor site was also assessed . Thirty-four Japanese patients with locally advanced SCCHN were eligible .  Docetaxel was administered as a 1-h i.v . infusion at 48 mg/m2 on day 1 ; cisplatin , 24 mg/m2/day ; 5-FU , 560 mg/m2/day and l-LV , 125 mg/body/day were delivered on days 1–4 by continuous i.v . infusion . This regimen was administered every 28 days . Patients who achieved a complete response ( CR ) after induction chemotherapy underwent radiation therapy alone . Ninety-one cycles were administered . The main hematological toxicity was neutropenia , classified as grade III or IV in 18.7 % of cycles . The most common non-hematologic toxicities included anorexia , stomatitis and alopecia . The clinical overall response rate to m-TPFL was 88.2 % , with 58.8 % CRs and 29.4 % partial responses . After definitive locoregional therapy , 25 of 34 patients were disease-free with preserved primary tumor site anatomy . Overall and progression-free survival rates at the 2-year follow-up are 92.8 and 75.3 % , respectively . Our m-TPFL regimen design ed for Japanese patients yielded excellent response rates with an acceptable toxicity profile in good-performance-status patients PURPOSE The primary aim of National Surgical Adjuvant Breast and Bowel Project ( NSABP ) B-28 was to determine whether four cycles of adjuvant paclitaxel ( PTX ) after four cycles of adjuvant doxorubicin/cyclophosphamide ( AC ) will prolong disease-free survival ( DFS ) and overall survival ( OS ) compared with four cycles of AC alone in patients with resected operable breast cancer and histologically positive axillary nodes . PATIENTS AND METHODS Between August 1995 and May 1998 , 3,060 patients were r and omly assigned ( AC , 1,529 ; AC followed by PTX [ AC -- > PTX ] , 1,531 ) . Patients > or = 50 years and those younger than 50 years with estrogen receptor ( ER ) or progesterone receptor ( PR ) -positive tumors also received tamoxifen for 5 years , starting with the first dose of AC . Postlumpectomy radiotherapy was m and ated . Postmastectomy or regional radiotherapy was prohibited . Median follow-up is 64.6 months . RESULTS The addition of PTX to AC significantly reduced the hazard for DFS event by 17 % ( relative risk [ RR ] , 0.83 ; 95 % CI , 0.72 to 0.95 ; P = .006 ) . Five-year DFS was 76 % + /- 2 % for patients r and omly assigned to AC -- > PTX compared with 72 % + /- 2 % for those r and omly assigned to AC . Improvement in OS was small and not statistically significant ( RR , 0.93 ; 95 % CI , 0.78 to 1.12 ; P = .46 ) . Five-year OS was 85 % + /- 2 % for both groups . Subset analysis of the effect of paclitaxel according to hormone receptors or tamoxifen administration did not reveal statistically significant interaction ( for DFS , P = .30 and P = .44 , respectively ) . Toxicity with the AC -- > PTX regimen was acceptable for the adjuvant setting . CONCLUSION The addition of PTX to AC result ed in significant improvement in DFS but no significant improvement in OS with acceptable toxicity . No significant interaction between treatment effect and receptor status or tamoxifen administration was observed PURPOSE The primary treatment modality for patients with carcinoma of the esophagus or gastroesophageal junction has been surgery , although primary radiation therapy with concurrent chemotherapy produces similar results . As both have curative potential , there has been great interest in the use of trimodality therapy . To this end , we compared survival , response , and patterns of failure of trimodality therapy to esophagectomy alone in patients with nonmetastatic esophageal cancer . PATIENTS AND METHODS Four hundred seventy-five eligible patients were planned for enrollment . Patients were r and omly assigned to either esophagectomy with node dissection alone or cisplatin 100 mg/m(2 ) and fluorouracil 1,000 mg/m(2)/d for 4 days on weeks 1 and 5 concurrent with radiation therapy ( 50.4 Gy total : 1.8 Gy/fraction over 5.6 weeks ) followed by esophagectomy with node dissection . RESULTS Fifty-six patients were enrolled between October 1997 and March 2000 , when the trial was closed due to poor accrual . Thirty patients were r and omly assigned to trimodality therapy and 26 were assigned to surgery alone . Patient and tumor characteristics were similar between groups . Treatment was generally well tolerated . Median follow-up was 6 years . An intent-to-treat analysis showed a median survival of 4.48 v 1.79 years in favor of trimodality therapy ( exact stratified log-rank , P = .002 ) . Five-year survival was 39 % ( 95 % CI , 21 % to 57 % ) v 16 % ( 95 % CI , 5 % to 33 % ) in favor of trimodality therapy . CONCLUSION The results from this trial reflect a long-term survival advantage with the use of chemoradiotherapy followed by surgery in the treatment of esophageal cancer , and support trimodality therapy as a st and ard of care for patients with this disease BACKGROUND Previous studies have demonstrated that African-Americans with colon cancer have worse overall and stage-specific survival rates than Caucasians . Such differences could reflect variation in access to health care , in tumor biology , or in treatment efficacy . Little is known about potential differences in chemotherapy-related toxicities between African-Americans and Caucasians . In this study , we examined survival and toxic effects among African-American and Caucasian patients enrolled in a large , r and omized phase III trial of adjuvant chemotherapy for resected colon cancer . METHODS We analyzed data on 3380 patients ( 344 African-Americans and 3036 Caucasians ) enrolled in a r and omized trial of adjuvant 5-fluorouracil-based chemotherapy in patients with stage II ( high risk ) and stage III colon cancer to evaluate differences in outcomes and toxicity . We compared disease-free survival ( DFS ) and overall survival ( OS ) between African-Americans and Caucasians by the Kaplan-Meier method , computed Cox proportional hazards by multivariable analysis , and compared treatment-related toxicity rates by Fisher 's exact test . All statistical tests were two-sided . RESULTS We found no differences in DFS or OS between African-American and Caucasian patients . Five-year DFS was 57 % ( 95 % confidence interval [ CI ] = 52 % to 62 % ) for African-Americans and 58 % ( 95 % CI = 56 % to 60 % ) for Caucasians ( P = .15 ) , and 5-year OS was 65 % ( 95 % CI = 60 % to 70 % ) for African-Americans and 66 % ( 95 % CI = 64 % to 68 % ) for Caucasians ( P = .38 ) . On multivariable analysis , no statistically significant difference in disease recurrence or death was detected between the racial/ethnic groups ( hazard ratios for African-Americans versus Caucasians : disease recurrence = 1.1 , 95 % CI = 0.9 to 1.3 ; death = 1.1 , 95 % CI = 0.9 to 1.3 ) . Treatment-related toxicity differed between the African-American and Caucasian patients , with African-Americans experiencing statistically significantly lower rates of diarrhea ( P<.001 ) , nausea ( P<.001 ) , vomiting ( P = .01 ) , stomatitis ( P<.001 ) , and overall toxicity ( P = .005 ) . CONCLUSIONS In this study of patients with similar access to health care re sources and treatment with adjuvant chemotherapy , we found similar 5-year DFS and OS in African-Americans and Caucasians with stage II and III colon cancer . The two groups derived similar benefits from adjuvant chemotherapy . Moreover , African-Americans appeared to experience less treatment-related toxicity PURPOSE Concurrent chemoradiotherapy is st and ard treatment for patients with inoperable stage III non-small-cell lung cancer ( NSCLC ) . A phase II study by the Southwest Oncology Group using consolidation docetaxel after cisplatin ( P ) , etoposide ( E ) , and radiation ( XRT ) result ed in a median survival time ( MST ) of 26 months . This r and omized phase III trial evaluated whether consolidation docetaxel was responsible for this improved survival . PATIENTS AND METHODS Eligible patients had stage IIIA or IIIB NSCLC , baseline performance status of 0 to 1 , forced expiratory volume in 1 second > or= 1 L , and less than 5 % weight loss . Patients received P 50 mg/m(2 ) intravenously ( IV ) on days 1 , 8 , 29 , and 36 and E 50 mg/m(2 ) IV on days 1 - 5 and 29 - 33 concurrently with chest XRT to 59.40 Gy . Patients who did not experience progression were r and omly assigned to docetaxel 75 mg/m(2 ) IV every 21 days for three cycles versus observation . The primary end point was to compare overall survival ( Kaplan-Meier analysis ) . RESULTS On the basis of evidence of futility , a data and safety monitoring board recommended early termination after an analysis of the initial 203 patients . Patient characteristics ( n = 203 ) were as follows : 34 % female ; median age , 63 years ; 39.4 % stage IIIA ; and 60.6 % stage IIIB . One hundred forty-seven ( 72.4 % ) of 203 patients were r and omly assigned to docetaxel ( n = 73 ) or observation ( n = 74 ) . Grade 3 to 5 toxicities during docetaxel included febrile neutropenia ( 10.9 % ) and pneumonitis ( 9.6 % ) ; 28.8 % of patients were hospitalized during docetaxel ( v 8.1 % in observation arm ) , and 5.5 % died as a result of docetaxel . The MST for all patients ( n = 203 ) was 21.7 months ; MST was 21.2 months for docetaxel arm compared with 23.2 months for observation arm ( P = .883 ) . CONCLUSION Consolidation docetaxel after PE/XRT results in increased toxicities but does not further improve survival compared with PE/XRT alone in patients with stage III inoperable NSCLC BACKGROUND Intravenous bolus fluorouracil plus leucovorin is the st and ard adjuvant treatment for colon cancer . The oral fluoropyrimidine capecitabine is an established alternative to bolus fluorouracil plus leucovorin as first-line treatment for metastatic colorectal cancer . We evaluated capecitabine in the adjuvant setting . METHODS We r and omly assigned a total of 1987 patients with resected stage III colon cancer to receive either oral capecitabine ( 1004 patients ) or bolus fluorouracil plus leucovorin ( Mayo Clinic regimen ; 983 patients ) over a period of 24 weeks . The primary efficacy end point was at least equivalence in disease-free survival ; the primary safety end point was the incidence of grade 3 or 4 toxic effects due to fluoropyrimidines . RESULTS Disease-free survival in the capecitabine group was at least equivalent to that in the fluorouracil-plus-leucovorin group ( in the intention-to-treat analysis , P<0.001 for the comparison of the upper limit of the hazard ratio with the noninferiority margin of 1.20 ) . Capecitabine improved relapse-free survival ( hazard ratio , 0.86 ; 95 percent confidence interval , 0.74 to 0.99 ; P=0.04 ) and was associated with significantly fewer adverse events than fluorouracil plus leucovorin ( P<0.001 ) . CONCLUSIONS Oral capecitabine is an effective alternative to intravenous fluorouracil plus leucovorin in the adjuvant treatment of colon cancer PURPOSE We examined data from a large clinical trial to determine if chemotherapy dosing according to actual body weight places obese patients at greater risk of toxicity . PATIENTS AND METHODS Cancer and Leukemia Group B ( CALGB ) study 8541 , a r and omized study of schedule and dose of adjuvant cyclophosphamide , doxorubicin , and fluorouracil ( CAF ) for stage II breast cancer patients with positive regional lymph nodes , provided data on 1,435 women for analysis . Using body-mass index ( BMI ) , we classified a woman as obese if her BMI was > or = 27.3 kg/m2 ; doses were considered weight-based if within 5 % of values calculated using actual weight . Our primary analysis concerned toxicity risks during cycle 1 . RESULTS Among women who received weight-based doses of the most dose-intensive CAF regimen , 47 % of obese and 51 % of nonobese women experienced severe hematologic toxicity ( grade > or = 3 ) during cycle 1 ( P = .51 , two-tailed ) . The overall risk ratio ( obese v nonobese ) of treatment failure among women who received weight-based doses during cycle 1 was 1.02 ( 95 % confidence interval , 0.83 to 1.26 ) , stratified by treatment and adjusted for number of positive nodes , menopausal status , hormone receptor status , and tumor size . The overall adjusted failure risk ratio ( weight-based v reduced initial doses ) was 0.73 ( 95 % confidence interval , 0.53 to 1.00 ) among obese women . CONCLUSION Obese patients initially dosed ( within 5 % ) by actual weight did not experience excess cycle 1 toxicity or worse outcome compared with nonobese women dosed similarly . The data suggest that obese women who received reduced doses in cycle 1 experienced worse failure-free survival . We recommend that initial doses of CAF be computed according to actual body weight PURPOSE The combination of doxorubicin and cyclophosphamide ( AC ) is a st and ard adjuvant chemotherapy regimen . Studies of docetaxel and cyclophosphamide ( TC ) in metastatic breast cancer ( MBC ) showed promise in MBC . In 1997 , we initiated a r and omized adjuvant trial of TC compared with st and ard-dose AC with a primary end point of disease-free survival ( DFS ) . PATIENTS AND METHODS Patients were eligible if they had stage I to III operable invasive breast cancer with complete surgical excision of the primary tumor . Between June 1997 and December 1999 , 1,016 patients were r and omly assigned to four cycles of either st and ard-dose AC ( 60 and 600 mg/m2 , respectively ; n = 510 ) or TC ( 75 and 600 mg/m2 , respectively ; n = 506 ) , administered intravenously every 3 weeks as adjuvant chemotherapy . Radiation therapy ( as indicated ) and tamoxifen , for patients with hormone receptor-positive disease , were administered after completion of chemotherapy . RESULTS Both treatment groups ( TC and AC ) were well balanced with respect to major prognostic factors . Patients were observed through 2005 for a median of 5.5 years . At 5 years , DFS rate was significantly superior for TC compared with AC ( 86 % v 80 % , respectively ; hazard ratio [ HR ] = 0.67 ; 95 % CI , 0.50 to 0.94 ; P = .015 ) . Overall survival rates for TC and AC were 90 % and 87 % , respectively ( HR = 0.76 ; 95 % CI , 0.52 to 1.1 ; P = .13 ) . More myalgia , arthralgia , edema , and febrile neutropenia occurred on the TC arm ; more nausea and vomiting occurred on the AC arm as well as one incident of congestive heart failure . CONCLUSION At 5 years , TC was associated with a superior DFS and a different toxicity profile compared with AC BACKGROUND A regimen of epirubicin , cisplatin , and infused fluorouracil ( ECF ) improves survival among patients with incurable locally advanced or metastatic gastric adenocarcinoma . We assessed whether the addition of a perioperative regimen of ECF to surgery improves outcomes among patients with potentially curable gastric cancer . METHODS We r and omly assigned patients with resectable adenocarcinoma of the stomach , esophagogastric junction , or lower esophagus to either perioperative chemotherapy and surgery ( 250 patients ) or surgery alone ( 253 patients ) . Chemotherapy consisted of three preoperative and three postoperative cycles of intravenous epirubicin ( 50 mg per square meter of body-surface area ) and cisplatin ( 60 mg per square meter ) on day 1 , and a continuous intravenous infusion of fluorouracil ( 200 mg per square meter per day ) for 21 days . The primary end point was overall survival . RESULTS  ECF-related adverse effects were similar to those previously reported among patients with advanced gastric cancer .  Rates of postoperative complications were similar in the perioperative-chemotherapy group and the surgery group ( 46 percent and 45 percent , respectively ) , as were the numbers of deaths within 30 days after surgery . The resected tumors were significantly smaller and less advanced in the perioperative-chemotherapy group . With a median follow-up of four years , 149 patients in the perioperative-chemotherapy group and 170 in the surgery group had died . As compared with the surgery group , the perioperative-chemotherapy group had a higher likelihood of overall survival ( hazard ratio for death , 0.75 ; 95 percent confidence interval , 0.60 to 0.93 ; P=0.009 ; five-year survival rate , 36 percent vs. 23 percent ) and of progression-free survival ( hazard ratio for progression , 0.66 ; 95 percent confidence interval , 0.53 to 0.81 ; P<0.001 ) . CONCLUSIONS In patients with operable gastric or lower esophageal adenocarcinomas , a perioperative regimen of ECF decreased tumor size and stage and significantly improved progression-free and overall survival . ( Current Controlled Trials number , IS RCT N93793971 [ controlled-trials.com ] . ) PURPOSE The Southwest Oncology Group ( SWOG ) coordinated an Intergroup study with the participation of Radiation Therapy Oncology Group ( RTOG ) , and Eastern Cooperative Oncology Group ( ECOG ) . This r and omized phase III trial compared chemoradiotherapy versus radiotherapy alone in patients with nasopharyngeal cancers . MATERIAL S AND METHODS Radiotherapy was administered in both arms : 1.8- to 2.0-Gy/d fractions Monday to Friday for 35 to 39 fractions for a total dose of 70 Gy . The investigational arm received chemotherapy with cisplatin 100 mg/m2 on days 1 , 22 , and 43 during radiotherapy ; postradiotherapy , chemotherapy with cisplatin 80 mg/m2 on day 1 and fluorouracil 1,000 mg/m2/d on days 1 to 4 was administered every 4 weeks for three courses . Patients were stratified by tumor stage , nodal stage , performance status , and histology . RESULTS Of 193 patients registered , 147 ( 69 radiotherapy and 78 chemoradiotherapy ) were eligible for primary analysis for survival and toxicity . The median progression-free survival ( PFS ) time was 15 months for eligible patients on the radiotherapy arm and was not reached for the chemo-radiotherapy group . The 3-year PFS rate was 24 % versus 69 % , respectively ( P < .001 ) . The median survival time was 34 months for the radiotherapy group and not reached for the chemo-radiotherapy group , and the 3-year survival rate was 47 % versus 78 % , respectively ( P = .005 ) . One hundred eighty-five patients were included in a secondary analysis for survival . The 3-year survival rate for patients r and omized to radiotherapy was 46 % , and for the chemoradiotherapy group was 76 % ( P < .001 ) . CONCLUSION We conclude that chemoradiotherapy is superior to radiotherapy alone for patients with advanced nasopharyngeal cancers with respect to PFS and overall survival BACKGROUND Chemoradiation became the st and ard of care for anal cancer after the ACT I trial . However , only two-thirds of patients achieved local control , with 5-year survival of 50 % ; therefore , better treatments are needed . We investigated whether replacing mitomycin with cisplatin in chemoradiation improves response , and whether maintenance chemotherapy after chemoradiation improves survival . METHODS In this 2 × 2 factorial trial , we enrolled patients with histologically confirmed squamous-cell carcinoma of the anus without metastatic disease from 59 centres in the UK . Patients were r and omly assigned to one of four groups , to receive either mitomycin ( 12 mg/m(2 ) on day 1 ) or cisplatin ( 60 mg/m(2 ) on days 1 and 29 ) , with fluorouracil ( 1000 mg/m(2 ) per day on days 1 - 4 and 29 - 32 ) and radiotherapy ( 50.4 Gy in 28 daily fractions ) ; with or without two courses of maintenance chemotherapy ( fluorouracil and cisplatin at weeks 11 and 14 ) . The r and om allocation was generated by computer and patients assigned by telephone . R and omisation was done by minimisation and stratified by tumour site , T and N stage , sex , age , and renal function . Neither patients nor investigators were masked to assignment . Primary endpoints were complete response at 26 weeks and acute toxic effects ( for chemoradiation ) , and progression-free survival ( for maintenance ) . The primary analyses were done by intention to treat . This study is registered at controlled-trials.com , number 26715889 . FINDINGS We enrolled 940 patients : 472 were assigned to mitomycin , of whom 246 were assigned to no maintenance , 226 to maintenance ; 468 were assigned to cisplatin , of whom 246 were assigned to no maintenance , 222 to maintenance . Median follow-up was 5.1 years ( IQR 3.9 - 6.9 ) . 391 of 432 ( 90.5 % ) patients in the mitomycin group versus 386 of 431 ( 89.6 % ) in the cisplatin group had a complete response at 26 weeks ( difference -0.9 % , 95 % CI -4.9 to 3.1 ; p=0.64 ) . Overall , toxic effects were similar in each group ( 334/472 [ 71 % ] for mitomycin vs 337/468 [ 72 % ] for cisplatin ) . The most common grade 3 - 4 toxic effects were skin ( 228/472 [ 48 % ] vs 222/468 [ 47 % ] ) , pain ( 122/472 [ 26 % ] vs 135/468 [ 29 % ] ) , haematological ( 124/472 [ 26 % ] vs 73/468 [ 16 % ] ) , and gastrointestinal ( 75/472 [ 16 % ] vs 85/468 [ 18 % ] ) . 3-year progression-free survival was 74 % ( 95 % CI 69 - 77 ; maintenance ) versus 73 % ( 95 % CI 68 - 77 ; no maintenance ; hazard ratio 0.95 , 95 % CI 0.75 - 1.21 ; p=0.70 ) . INTERPRETATION The results of our trial -- the largest in anal cancer to date --show that fluorouracil and mitomycin with 50.4 Gy radiotherapy in 28 daily fractions should remain st and ard practice in the UK . FUNDING Cancer Research UK BACKGROUND Despite aggressive local therapy , patients with locally advanced bladder cancer are at significant risk for metastases . We evaluated the ability of neoadjuvant chemotherapy to improve the outcome in patients with locally advanced bladder cancer who were treated with radical cystectomy .  METHODS Patients were enrolled if they had muscle-invasive bladder cancer ( stage T2 to T4a ) and were to be treated with radical cystectomy .  They were stratified according to age ( less than 65 years vs. 65 years or older ) and stage ( superficial muscle invasion vs. more extensive disease ) and were r and omly assigned to radical cystectomy alone or three cycles of methotrexate , vinblastine , doxorubicin , and cisplatin followed by radical cystectomy . RESULTS We enrolled 317 patients over an 11-year period , 10 of whom were found to be ineligible ; thus , 154 were assigned to receive surgery alone and 153 to receive combination therapy . According to an intention-to-treat analysis , the median survival among patients assigned to surgery alone was 46 months , as compared with 77 months among patients assigned to combination therapy ( P=0.06 by a two-sided stratified log-rank test ) . In both groups , improved survival was associated with the absence of residual cancer in the cystectomy specimen . Significantly more patients in the combination-therapy group had no residual disease than patients in the cystectomy group ( 38 percent vs. 15 percent , P<0.001 ) . CONCLUSIONS As compared with radical cystectomy alone , the use of neoadjuvant methotrexate , vinblastine , doxorubicin , and cisplatin followed by radical cystectomy increases the likelihood of eliminating residual cancer in the cystectomy specimen and is associated with improved survival among patients with locally advanced bladder cancer PURPOSE This single centre , open labelled , r and omised non-inferiority trial compared concurrent chemoradiotherapy with carboplatin versus st and ard concurrent chemoradiotherapy with cisplatin in patients with locoregionally advanced nasopharyngeal cancer ( NPC ) . PATIENTS AND METHODS From August 1999 to December 2004 , 206 patients with locally advanced NPC were r and omised with 101 to cisplatin arm and 105 to carboplatin arm . Planned radiotherapy was the same in both groups . All the patients were evaluated for toxicity and survival according to the as-treated principle . RESULTS With a median follow-up of 26.3 months ( range 3 - 74.6 months ) , 59 % of patients in the cisplatin arm completed the planned concurrent chemoradiation treatment , compared to 73 % in the carboplatin arm . Forty-two percent of cisplatin patients completed the 3 cycles of adjuvant therapy compared to 70 % in the carboplatin group . There were more renal toxicity , leucopenia , and anaemia in the cisplatin group , and more thrombocytopenia in the carboplatin arm . The 3 year disease free survival rates were 63.4 % for the cisplatin group and 60.9 % for the carboplatin group ( p=0.9613 ) ( HR 0.70 , 95 % confidence interval ( CI ) : 0.50 - 0.98 ) . The 3 year overall survival rates were 77.7 % and 79.2 % for cisplatin and carboplatin groups , respectively ( p=0.9884 ) ( HR 0.83 , 95 % CI : 0.63 - 1.010 ) . CONCLUSION We concluded that the tolerability of carboplatin based regimen is better than that of the cisplatin regimen . Moreover , the treatment efficacy of carboplatin arm is not different from the st and ard regimen in the treatment of locoregional advanced stage NPC Meta‐ analysis data demonstrate a 5 % absolute survival benefit for neoadjuvant chemotherapy ( NAC ) using cisplatin‐based combination regimens in the radical treatment of muscle‐invasive bladder cancer ( MIBC ) . However , there are no r and omized , controlled trial data on the optimum regimen . Accelerated methotrexate , vinblastine , doxorubicin , and cisplatin ( AMVAC ) is a dose‐intense regimen that has the potential to minimize delays to definitive , potentially curative therapy . A retrospective analysis is presented of the efficacy and toxicity  of AMVAC as NAC in patients with MIBC and its impact on the patient pathway
target: This review shows that a significant proportion of patients in curative-intent clinical trials experience toxicities that result in dose modifications-dose reduction , dose delays or missed doses-despite strict selection criteria and intense monitoring .
background: Toxicities of systemic cancer therapies are often less frequently observed in clinical trials than in clinical practice , due to the careful selection of patients with fewer comorbidities .
  Although guidelines exist for the estimation of chemotherapy dose , clinical factors like age , comorbid illness and extremes of body habitus are not considered in the method of dose calculation , which can result in significant toxicity .