Toxicity and health-related quality of life in breast cancer patients receiving adjuvant docetaxel, doxorubicin, cyclophosphamide (TAC) or 5-fluorouracil, doxorubicin and cyclophosphamide (FAC): impact of adding primary prophylactic granulocyte-colony stimulating factor to the TAC regimen. Epirubicin–vinorelbine vs FEC100 for node-positive, early breast cancer: French Adjuvant Study Group 09 trial Docetaxel With Cyclophosphamide Is Associated With an Overall Survival Benefit Compared With Doxorubicin and Cyclophosphamide: 7-Year Follow-Up of US Oncology Research Trial 9735. Randomised trial: survival benefit and safety of adjuvant dose-dense chemotherapy for node-positive breast cancer Pegfilgrastim +/- ciprofloxacin for primary prophylaxis with TAC (docetaxel/doxorubicin/cyclophosphamide) chemotherapy for breast cancer. Results from the GEPARTRIO study. A novel continuous infusional 5-fluorouracil-based chemotherapy regimen compared with conventional chemotherapy in the neo-adjuvant treatment of early breast cancer: 5 year results of the TOPIC trial. Antiemetic efficacy of high-dose metoclopramide: randomized trials with placebo and prochlorperazine in patients with chemotherapy-induced nausea and vomiting. Complete hormonal blockade versus epirubicin-based chemotherapy in premenopausal, one to three node-positive, and hormone-receptor positive, early breast cancer patients: 7-year follow-up results of French Adjuvant Study Group 06 randomised trial. Dose-dense adjuvant chemotherapy in early breast cancer patients: results from a randomized trial. Postoperative dose-dense sequential chemotherapy with epirubicin, followed by CMF with or without paclitaxel, in patients with high-risk operable breast cancer: a randomized phase III study conducted by the Hellenic Cooperative Oncology Group. Cisplatin plus oral etoposide (EoP) combination is more effective than paclitaxel in patients with advanced breast cancer pretreated with anthracyclines: a randomised phase III trial of Turkish Oncology Group Accelerated versus standard cyclophosphamide, epirubicin and 5-fluorouracil or cyclophosphamide, methotrexate and 5-fluorouracil: a randomized phase III trial in locally advanced breast cancer. Paclitaxel and epirubicin versus paclitaxel and carboplatin as first-line chemotherapy in patients with advanced breast cancer: a phase III study conducted by the Hellenic Cooperative Oncology Group. Leuprorelin acetate every-3-months depot versus cyclophosphamide, methotrexate, and fluorouracil as adjuvant treatment in premenopausal patients with node-positive breast cancer: the TABLE study. Comparison of rapidly cycled tandem high-dose chemotherapy plus peripheral-blood stem-cell support versus dose-dense conventional chemotherapy for adjuvant treatment of high-risk breast cancer: results of a multicentre phase III trial Phase III study of intravenous vinorelbine in combination with epirubicin versus epirubicin alone in patients with advanced breast cancer: a Scandinavian Breast Group Trial (SBG9403). Weekly paclitaxel improves pathologic complete remission in operable breast cancer when compared with paclitaxel once every 3 weeks. Doxorubicin with cyclophosphamide followed by docetaxel every 21 days compared with doxorubicin and docetaxel every 14 days as preoperative treatment in operable breast cancer: the GEPARDUO study of the German Breast Group. Neoadjuvant vinorelbine/epirubicin (VE) versus standard adriamycin/cyclophosphamide (AC) in operable breast cancer: analysis of response and tolerability in a randomised phase III trial (TOPIC 2). A phase III randomized trial comparing adjuvant concomitant chemoradiotherapy versus standard adjuvant chemotherapy followed by radiotherapy in operable node-positive breast cancer: final results. Intensive dose-dense compared with high-dose adjuvant chemotherapy for high-risk operable breast cancer: Southwest Oncology Group/Intergroup study 9623. Sequenced compared with simultaneous anthracycline and cyclophosphamide in high-risk stage I and II breast cancer: final analysis from INT-0137 (S9313). The role of randomization in clinical trials. Adjuvant chemotherapy with sequential or concurrent anthracycline and docetaxel: Breast International Group 02-98 randomized trial. Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with breast cancer after moderately emetogenic chemotherapy. Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. Phase III trial comparing three doses of docetaxel for second-line treatment of advanced breast cancer. Improved outcome from substituting methotrexate with epirubicin: results from a randomised comparison of CMF versus CEF in patients with primary breast cancer. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. Addition of either lonidamine or granulocyte colony-stimulating factor does not improve survival in early breast cancer patients treated with high-dose epirubicin and cyclophosphamide. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. Phase III randomized trial of doxorubicin and docetaxel versus doxorubicin and cyclophosphamide as primary medical therapy in women with breast cancer: an anglo-celtic cooperative oncology group study. Neoadjuvant vinorelbine-capecitabine versus docetaxel-doxorubicin-cyclophosphamide in early nonresponsive breast cancer: phase III randomized GeparTrio trial. Users' guides to the medical literature. XIII. How to use an article on economic analysis of clinical practice. B. What are the results and will they help me in caring for my patients? Evidence-Based Medicine Working Group. Phase III study to evaluate the use of high‐dose chemotherapy as consolidation of treatment for high‐risk postoperative breast cancer: Japan Clinical Oncology Group study, JCOG 9208
BACKGROUND The aim of the study was to analyse the toxicity and health related quality of life ( HRQoL ) of breast cancer patients treated with FAC ( 5-fluorouracil , doxorubicin , cyclophosphamide ) and TAC ( docetaxel , doxorubicin , cyclophosphamide ) with and without primary prophylactic G-CSF ( PPG ) .  PATIENTS AND METHODS This was a phase III study to compare FAC and TAC as adjuvant treatment of high-risk node-negative breast cancer patients . After the entry of the first 237 patients , the protocol was amended to include PPG in the TAC arm due to the high incidence of febrile neutropenia . A total of 1047 evaluable patients from 49 centres in Spain , two in Pol and and four in Germany were included in the trial .  Side-effects and the scores of the EORTC QLQ-C30 and QLQ BR-23 question naires were compared in the three groups ( FAC , TAC pre-amendment and TAC post-amendment ) . RESULTS The addition of PPG to TAC significantly reduced the incidence of neutropenic fever , grade 2 - 4 anaemia , asthenia , anorexia , nail disorders , stomatitis , myalgia and dysgeusia . Patient QoL decreased during chemotherapy , more with TAC than FAC , but returned to baseline values afterwards . The addition of PPG to TAC significantly reduced the percentage of patients with clinical ly relevant Global Health Status deterioration ( 10 or more points over baseline value ) at the end of chemotherapy ( 64 % versus 46 % , P<0.03 ) . CONCLUSIONS The addition of PPG significantly reduces the incidence of neutropenic fever associated with TAC chemotherapy as well as that of some TAC-induced haematological and extrahaematological side-effects . The HRQoL of patients treated with TAC is worse than that of those treated with FAC but improves with the addition of PPG , particularly in the final part of chemotherapy treatment The aim of the study was to compare our reference adjuvant chemotherapy , FEC100 ( fluorouracil 500 mg m−2 , epirubicin 100 mg m−2 and cyclophosphamide 500 mg m−2 , six cycles every 21 days ) , to an epirubicin – vinorelbine ( Epi-Vnr ) combination for early , poor-prognosis breast cancer patients . Patients ( 482 ) were r and omised to receive FEC100 , or Epi-Vnr ( epirubicin 50 mg m−2 day 1 and vinorelbine 25 mg m−2 , days 1 and 8 , six cycles every 21 days ) . The 7-year disease-free survival rates were 59.4 and 58.8 % , respectively ( P=0.47 ) . The relative dose intensity of planned epirubicin doses was 89.1 % with FEC100 and 88.9 % with Epi-Vnr . There were significantly more grade s 3–4 neutropenia ( P=0.009 ) with Epi-Vnr , and significantly more nausea-vomiting ( P<0.0001 ) , stomatitis ( P=0.0007 ) and alopecia ( P<0.0001 ) with FEC100 . No cases of congestive heart failure were reported , whereas four decreases in left ventricular ejection fraction occurred after FEC100 and five after Epi-Vnr . One case of acute myeloblastic leukaemia was registered in the FEC100 arm . After 7 years of follow-up , there was no difference between treatment arms . Epi-Vnr regimen provided a good efficacy in such poor-prognosis breast cancer patients , and could be an alternative to FEC100 , taking into account respective safety profiles of both regimens PURPOSE We previously reported that four cycles of docetaxel/cyclophosphamide ( TC ) produced superior disease-free survival ( DFS ) compared with four cycles of doxorubicin/cyclophosphamide ( AC ) in early breast cancer . Older women are under-represented in adjuvant chemotherapy trials . In our trial 16 % of patients were > or = 65 years . We now report 7-year results for DFS and overall survival ( OS ) as well as the impact of age , hormone receptor status , and HER2 status on outcome and toxicity . PATIENTS AND METHODS Patients were r and omly assigned to receive either four cycles of st and ard-dose AC ( 60/600 mg/m(2 ) ; n = 510 ) , or TC ( 75/600 mg/m(2 ) ; n = 506 ) , administered by intravenous infusion every 3 weeks . RESULTS The median age in women younger than 65 , was 50 years ( range , 27 to 64 ) and for women > or = 65 was 69 years ( range , 65 to 77 ) . Baseline characteristics in the two age subgroups were generally well matched , except that older women tended to have more lymph node involvement . At a median of 7 years follow-up , the difference in DFS between TC and AC was significant ( 81 % TC v 75 % AC ; P = .033 ; hazard ratio [ HR ] , 0.74 ; 95 % CI 0.56 to 0.98 ) as was OS ( 87 % TC v 82 % AC ; P = .032 ; HR , 0.69 ; 95 % CI , 0.50 to 0.97 ) . TC was superior in older patients as well as younger patients . There was no interaction of hormone-receptor status or HER-2 status and treatment . Older women experienced more febrile neutropenia with TC and more anemia with AC . CONCLUSION With longer follow-up , four cycles of TC was superior to st and ard AC ( DFS and OS ) and was a tolerable regimen in both older and younger patients We evaluated the survival benefit , safety , feasibility , and tolerability of dose-dense ( DD ) adjuvant chemotherapy with epirubicin and paclitaxel for women with node-positive primary breast cancer . R and omised patients ( n=216 ) received DD or conventional-schedule ( CS ) chemotherapy . Dose-dense regimen patients ( n=108 ) received epirubicin 90 mg m−2 plus paclitaxel 175 mg m−2 in four 14-day cycles , then cyclophosphamide 600 mg m−2 , methotrexate 40 mg m−2 , and fluorouracil 600 mg m−2 ( CMF 600/40/600 ) in three 14-day cycles , plus filgrastim 5 μg kg day−1 as growth support in every cycle . Conventional-schedule regimen patients ( n=108 ) received epirubicin 90 mg m−2 plus cyclophosphamide 600 mg m−2 in four 21-day cycles , then CMF 600/40/600 in three 21-day cycles , plus filgrastim if required . After a median follow-up of 38.4 months , 71 patients ( 33 % ) relapsed or died : DD , 33 patients ( 15 deaths ) ; CS , 38 patients ( 22 deaths ) . Dose dense showed a trend for improved disease-free survival ( DFS ) and overall survival ( OS ) . Four-year rates of DFS and OS were 64 and 85 % for DD , and 58 and 75 % for CS . All seven cycles were administered to 208 patients ( 96 % ) . Rates of cycle delay , discontinuation , dose reduction , and adverse events were similar in both groups . Dose-dense sequential chemotherapy with epirubicin/paclitaxel then CMF , supported by filgrastim , is safe and improves survival for patients with node-positive breast cancer BACKGROUND TAC ( docetaxel/doxorubicin/cyclophosphamide ) is associated with high incidences of grade 4 neutropenia and febrile neutropenia ( FN ) . This analysis compared the efficacies of four regimens for primary prophylaxis of FN and related toxic effects in breast cancer patients receiving neoadjuvant TAC . PATIENTS AND METHODS Patients with stage T2-T4 primary breast cancer were scheduled to receive 6 - 8 cycles of TAC .  Primary prophylaxis was : ciprofloxacin 500 mg orally twice daily on days 5 - 14 ( n = 253 patients ; 1478 cycles ) , daily granulocyte colony-stimulating factor ( G-CSF ) ( filgrastim 5 microg/kg/day or lenograstim 150 microg/m(2)/day ) on days 5 - 10 ( n = 377 ; 2400 cycles ) , pegfilgrastim 6 mg on day 2 ( n = 305 ; 1930 cycles ) , or pegfilgrastim plus ciprofloxacin ( n = 321 ; 1890 cycles ) . RESULTS Pegfilgrastim with/without ciprofloxacin was significantly more effective than daily G-CSF or ciprofloxacin in preventing FN ( 5 % and 7 % versus 18 % and 22 % of patients ; all P < 0.001 ) , grade 4 neutropenia , and leukopenia .  Pegfilgrastim plus ciprofloxacin completely prevented first cycle FN ( P < 0.01 versus pegfilgrastim alone ) and fatal neutropenic events . CONCLUSION Ciprofloxacin alone , or daily G-CSF from day 5 - 10 ( as in common practice ) , provided suboptimal protection against FN and related toxic effects in patients receiving TAC . Pegfilgrastim was significantly more effective in this setting , especially if given with ciprofloxacin BACKGROUND To compare the efficacy of continuous infusional 5-fluorouracil (5-FU)-based chemotherapy against conventional bolus chemotherapy in the preoperative treatment of patients with large operable early breast cancer . PATIENTS AND METHODS Four hundred and twenty-six women with histologically proven 3 cm invasive early breast cancer were r and omised to receive pre-operative infusional 5-FU 200 mg/m(2 ) by daily 24 h continuous infusion via a Hickman line for 18 weeks with epirubicin 60 mg/m(2 ) intravenous ( i.v . ) bolus on day 1 and cisplatin 60 mg/m(2 ) i.v . bolus on day 1 , both repeating 3-weekly ( infusional ECisF ) , or conventional bolus doxorubicin 60 mg/m(2 ) i.v . on day 1 and cyclophosphamide 600 mg/m(2 ) i.v . on day 1 , both repeating 3-weekly ( AC ) , both schedules for six courses . Patients subsequently had local therapy ( surgery or radiotherapy or both ) and tamoxifen 20 mg orally daily as appropriate . RESULTS The 5 year results for AC and infusional ECisF , respectively , were as follows : overall response , 75 % and 77 % ; complete clinical remission , 31 % and 34 % ; pathological complete remission ( pathCR ) , 16 % for both ; and pathCR with residual ductal carcinoma in situ ( DCIS ) , 25 % and 24 % . Mastectomy rates were 37 % and 34 % , respectively . Five-year overall survival was 74 % for AC and 82 % for infusional ECisF ( hazard ratio 0.76 , 95 % confidence interval 0.51 - 1.13 ; P = 0.18 ) . Both treatments were well tolerated . Grade III/IV lethargy , vomiting , alopecia and plantar-palmar erythema were significantly greater for infusional ECisF ; grade III/IV leucopenia was significantly greater for AC . CONCLUSIONS Preoperative continuous infusional 5-FU-based chemotherapy is no more active than conventional AC for early breast cancer ; with a median 5 year follow-up , the infusion-based schedule shows a non-significant trend towards improved survival In a study of the effectiveness of high intravenous doses of metoclopramide as an antiemetic , 41 patients with advanced cancer who were being treated with cisplatin  were entered into two double-blind trials . In the first trial patients were r and omly assigned to receive either metoclopramide or placebo , and in the second trial they received either metoclopramide or prochlorperazine . Patients given metoclopramide had significantly fewer episodes of emesis than patients given placebo ( medians , 1.0 vs. 10.5 ; P = 0.001 ) or prochlorperazine ( medians , 1.5 vs. 12.0 ; P = 0.005 ) . Metoclopramide was superior to placebo and to prochlorperazine in reducing the volume of emesis ( P = 0.001 and P = 0.022 , respectively ) and was more effective than placebo in shortening the duration of nausea ( P = 0.042 ) and vomiting ( P = 0.028 ) . Side effects from metoclopramide were minor , with mild sedation frequently observed ; one patient had a brief extrapyramidal reaction . We conclude that metoclopramide in high intravenous doses has greater antiemetic activity than placebo or prochlorperazine in patients receiving cisplatin chemotherapy BACKGROUND The purpose of this study was to determine optimal adjuvant therapy between complete hormonal blockade in premenopausal patients with hormone receptor positive breast cancer and one to three positive nodes . PATIENTS AND METHODS We r and omised 333 patients to receive either LHRH agonist ( triptorelin 3.75 mg i.m . , monthly ) plus tamoxifen 30 mg/day for 3 years ( TAM-LHRHa , n=164 ) , or fluorouracil 500 mg/m2 , epirubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 every 21 days for six cycles , without any hormonal treatment ( FEC50 , n=169 ) . RESULTS The 7-year disease-free survival ( DFS ) was 76 % with TAM-LHRHa , and 72 % with FEC50 ( P=0.13 ) . The 7-year overall survival ( OS ) was 91 % and 88 % , respectively ( P=0.20 ) . The multivariate analysis confirmed that both treatments were not different for DFS and OS ( P=0.83 and P=0.41 , respectively ) . Amenorrhoea occurred in 64 % of patients treated with FEC50 ; it was temporary in 58 % of cases after hormonotherapy and in 31 % after chemotherapy . CONCLUSION In intermediate-risk breast cancer , complete hormonal blockade and chemotherapy provided similar outcomes .  Hormonal treatment is an alternative to chemotherapy in hormone-sensitive patients , considering the preference of patients in terms of quality of life BACKGROUND To determine whether a dose-dense regimen improves outcome in early breast cancer patients , we compared outcomes with the same fluorouracil , epirubicin , and cyclophosphamide ( FEC ) chemotherapeutic regimen administered every 3 weeks ( FEC21 ) or administered every 2 weeks ( FEC14 including support with filgrastim , a granulocyte colony-stimulating factor ) in a multicenter phase III r and omized trial . METHODS A total of 1214 patients with early-stage breast cancer were r and omly assigned to receive six cycles of FEC14 ( 604 patients ) or of FEC21 ( 610 patients ) . Study endpoints were overall survival and event-free survival . Associations were assessed by multivariable analysis with adjustment for age ; tumor size ; grade ; proliferative rate ; and menopausal , lymph node , estrogen receptor , and progesterone receptor status . All statistical tests were two-sided . RESULTS Patients in the FEC14 arm had fewer dose reductions or treatment delays or discontinuation ( 26 % ) than those in the FEC21 arm ( 33 % ) ( difference = 7 % , 95 % confidence interval [ CI ] = 2 % to 12 % ; P = .008 ) . FEC14 therapy , compared with FEC21 therapy , was associated with more asthenia ( 36 % versus 29 % , difference = 7 % , 95 % CI = 2 % to 12 % ; P = .01 ) , bone pain ( 33 % versus 4 % , difference = 29 % , 95 % CI = 25 % to 33 % ; P < .001 ) , anemia ( 38 % versus 19 % , difference = 19 % , 95 % CI = 14 % to 24 % ; P < .001 ) , and thrombocytopenia ( 8 % versus 2 % , difference = 6 % , 95 % CI = 4 % to 9 % ; P < .001 ) , but with less leukopenia ( 12 % versus 45 % , difference = 33 % , 95 % CI = 28 % to 37 % ; P < .001 ) . No acute myelogenous leukemia or myelodysplastic syndrome was observed . At a median follow-up of 10.4 years , no statistically significant difference in the hazard of death ( hazard ratio [ HR ] = 0.87 , 95 % CI = 0.67 to 1.13 ) or recurrence ( HR = 0.88 , 95 % CI = 0.71 to 1.08 ) was found between FEC14 and FEC21 groups after adjustment by multivariable analysis . Although the study was underpowered for subset analysis , we found no evidence that the effect of the treatment type was associated with any of the potential prognostic factors . CONCLUSION Our results support the long-term safety of FEC14 chemotherapy as an adjuvant treatment of breast cancer . However , this therapy was not associated with improved outcome , but because of the limited statistical power of our study , we can not rule out a modest improvement in outcome associated with FEC14 therapy PURPOSE The aim of this study was to explore the effect of dose-dense sequential chemotherapy with or without paclitaxel primarily on disease-free survival ( DFS ) and secondarily on overall survival ( OS ) in patients with high-risk operable breast cancer . PATIENTS AND METHODS From June 1997 until November 2000 , 604 patients with T1 - 3N1M0 or T3N0M0 tumors were r and omized to three cycles of epirubicin 110 mg/m2 followed by three cycles of paclitaxel 250 mg/m2 followed by three cycles of ' intensified ' CMF ( cyclophosphamide 840 mg/m2 , methotrexate 47 mg/m2 and fluorouracil 840 mg/m2 ) ( group A ) , or to four cycles of epirubicin followed by four cycles of CMF , as in group A ( group B ) . All cycles were given every 2 weeks with granulocyte colony-stimulating factor support . RESULTS A total of 595 patients were eligible .  Median follow-up was 61.7 months for group A and 62 months for group B. The 3-year DFS was 80 % in group A and 77 % in group B. Survival rates were 93 % and 90 % , respectively . The effect of treatment on the hazard of death was different according to hormonal receptor status . More specifically , in patients with negative receptor status the hazard of death was significantly higher for group B ( hazard ratio 2.42 ) . Both regimens were well tolerated and severe acute side-effects were infrequent . No cases of severe cardiotoxicity or acute leukemia were recorded . CONCLUSIONS The present study failed to demonstrate a significant difference in DFS or OS between the two treatment groups . However , our study has shown clearly that high-dose paclitaxel can be safely incorporated to dose-dense sequential chemotherapy Our objective was to determine whether oral etoposide and cisplatin combination ( EoP ) is superior to paclitaxel in the treatment of advanced breast cancer ( ABC ) patients pretreated with anthracyclines . From December 1997 to August 2003 , 201 patients were r and omised , 100 to EoP and 101 to paclitaxel arms . Four patients in each arm were ineligible . The doses of etoposide and cisplatin were 50 mg p.o . twice a day for 7 days and 70 mg m−2 intravenously ( i.v . ) on day 1 , respectively , and it was 175 mg m−2 on day 1 for paclitaxel . Both treatments were repeated every 3 weeks . A median of four cycles of study treatment was given in both arms . The response rate obtained in the EoP arm was significantly higher ( 36.3 vs 22.2 % ; P=0.038 ) . Median response duration was longer for the EoP arm ( 7 vs 4 months ) ( P=0.132 ) . Also , time to progression was significantly in favour of the EoP arm ( 5.5 vs 3.9 months ; P=0.003 ) . Median overall survival was again significantly longer in the EoP arm ( 14 vs 9.5 months ; P=0.039 ) . Toxicity profile of both groups was similar . Two patients in each arm were lost due to febrile neutropenia . The observed activity and acceptable toxicity of EoP endorses the employment of this combination in the treatment of ABC following anthracyclines BACKGROUND The purpose of this study was to evaluate the impact of a dose-dense primary chemotherapy on pathological response rate ( pCR ) in patients with locally advanced breast cancer ( LABC ) treated with combined modality therapy . PATIENTS AND METHODS Stage IIIA/IIIB patients received three courses of induction chemotherapy ( ICT ) with cyclophosphamide , epirubicin and 5-fluorouracil ( CEF ) followed by local therapy ( total mastectomy or segmental mastectomy with axillary nodes dissection ) and adjuvant chemotherapy ( ACT ) with three courses of CEF alternated with three courses of cyclophosphamide , methotrexate , 5-fluorouracil ( CMF ) .  Patients were r and omized to receive ICT and ACT every 3 weeks ( arm A , ' st and ard treatment ' ) or every 2 weeks with granulocyte-macrophage colony-stimulating factor ( GM-CSF ) support ( arm B , ' dose-dense treatment ' ) . In both arms radiotherapy was administered after the end of chemotherapy ( in selected cases ) and patients with hormonal receptor-positive tumors received tamoxifen for 5 years . RESULTS A total of 150 patients were r and omized ( 77 arm A and 73 arm B ) and demographics were well balanced between the two arms . Compliance to treatment was excellent : 95 % and 93 % of patients in arms A and B , respectively , completed the treatment program with no modification or delay . Median duration of treatment ( ICT+local+ACT ) was 183 days ( range 0 - 265 ) in arm A and 139 days ( 0 - 226 ) in arm B. The average relative dose intensity ( ARDI ) of chemotherapy was 1.3 with a 30 % increase in the dose intensity in arm B in comparison with arm A. No difference in clinical [ 62 % ; 95 % confidence interval ( CI ) 49 % to 73.2 % ] and pathological response rates to ICT was observed between the two arms . Median follow-up was 5 years ( range 1 - 96 months ) ; median disease-free survivals were 4.8 years in arm A and 4.5 years in arm B. Median overall survival was 7.8 years in st and ard therapy : this figure has not yet been reached in the dose-dense treatment . CONCLUSIONS In LABC a dose-dense regimen , while allowing a 30 % increase in the dose intensity of chemotherapy , did not provide significant improvement in pathological response rates . However , accelerated chemotherapy reduced the duration of the combined-modality program ( 6.1 versus 4.6 months ) with no additional toxicities BACKGROUND To compare survival between patients with advanced breast cancer ( ABC ) treated with epirubicin/paclitaxel ( Taxol ) or paclitaxel/carboplatin ( Cp ) chemotherapy . PATIENTS AND METHODS From January 1999 to April 2002 , 327 eligible patients with ABC were r and omized to receive either paclitaxel 175 mg/m(2 ) in a 3-h infusion followed by epirubicin ( EPI ) 80 mg/m(2 ) ( group A ) or paclitaxel , as in group A , followed by Cp at an AUC of 6 mg x min/ml ( group B ) every 3 weeks for six cycles . RESULTS After a median follow-up of 23.5 months , median survival was not significantly different between the two groups ( 22.4 months versus 27.8 months , P=0.25 ) , whereas median time to treatment failure was significantly longer in patients treated with paclitaxel/Cp ( 8.1 months in group A versus 10.8 months in group B , P=0.04 ) . Both regimens were well tolerated . In total , 39 patients ( 24 % ) in group A and 46 ( 29 % ) in group B suffered at least one severe side-effect . Quality -of-life assessment and cost analysis did not reveal any significant differences between the two groups . CONCLUSION Our study suggests that the paclitaxel/Cp combination is an effective therapeutic alternative for patients with ABC in which anthracycline administration has the potential of being harmful PURPOSE Ovarian suppression with luteinizing hormone-releasing hormone ( LHRH ) agonists is an effective adjuvant treatment for premenopausal women with estrogen receptor ( ER ) -positive breast cancer . Whereas monthly LHRH agonist therapy has been well established , the value of every-3-months ( 3-monthly ) formulations is unclear . PATIENTS AND METHODS This r and omized phase III trial was performed to compare the 3-monthly depot LHRH agonist leuprorelin acetate ( LAD-3 M ; n = 299 ) and chemotherapy with cyclophosphamide , methotrexate , and fluorouracil ( CMF ; n = 300 ) in pre- or perimenopausal patients with ER-positive , node-positive breast cancer . RESULTS With a median follow-up of 5.8 years , recurrence-free survival was similar for patients treated with LAD-3 M or CMF ( hazard ratio [ HR ] , 1.19 ; 95 % CI , 0.94 to 1.51 ; P = .15 ) . There was no substantial heterogeneity in the relative treatment effect among subgroups defined by age , progesterone receptor ( PR ) status , nodal status , hormone levels , or menstrual recovery after treatment . Exploratory overall survival analysis favored LAD-3 M ( HR , 1.50 ; 95 % CI , 1.13 to 1.99 ; P = .005 ) . Chemotherapy-related adverse effects such as nausea , vomiting , and alopecia were more common with CMF , whereas symptoms of estrogen suppression such as hot flushes and sweating were initially more pronounced with LAD-3 M . CONCLUSION The 3-monthly depot LHRH-agonist leuprorelin acetate is an effective adjuvant treatment in premenopausal patients with hormone receptor-positive , node-positive breast cancer that is not inferior to CMF BACKGROUND Breast cancer with extensive axillary-lymph-node involvement has a poor prognosis after conventional treatment . In trials with historical controls , high-dose chemotherapy produced improved outcomes . We compared an intensive double-cycle high-dose chemotherapy regimen with an accelerated conventionally dosed regimen in high-risk breast cancer in a multicentre trial . METHODS Patients with at least nine positive nodes were r and omly assigned either two courses of accelerated ( 2-week intervals , with filgrastim support ) , conventionally dosed epirubicin and cyclophosphamide followed by two courses of high-dose chemotherapy ( epirubicin , cyclophosphamide , and thiotepa supported by peripheral-blood progenitors ) or four identical cycles of epirubicin and cyclophosphamide followed by three cycles of accelerated cyclophosphamide , methotrexate , and fluorouracil . The primary endpoint was event-free survival . Analyses were done both by intention to treat and per protocol . FINDINGS 403 patients were enrolled ; 201 were assigned high-dose chemotherapy and 202 conventional treatment . The mean number of positive nodes was 17.6 , and median follow-up was 48.6 months . 4-year event-free survival ( intention-to-treat analysis ) was 60 % ( 95 % CI 53 - 67 ) in the high-dose chemotherapy group and 44 % ( 37 - 52 ) in the control group ( p=0.00069 ) . The corresponding overall survival was 75 % ( 69 - 82 ) versus 70 % ( 64 - 77 ; p=0.02 ) . There were no treatment-related deaths . INTERPRETATION Our finding of significant improvements in both event-free and overall survival for high-dose chemotherapy compared with a dose-dense conventional regimen contrasts with the results of other studies . The discrepancy might be due partly to design differences ( t and em , brief induction ) between our regimen and those studied in other trials . This approach merits further study PURPOSE To determine whether the addition of intravenous ( IV ) vinorelbine to epirubicin increased the progression-free survival in first-line treatment of metastatic breast cancer . PATIENTS AND METHODS A total of 387 patients were r and omly assigned to receive IV epirubicin 90 mg/m(2 ) on day 1 and vinorelbine 25 mg/m(2 ) on days 1 and 8 , or epirubicin 90 mg/m(2 ) IV on day 1 . Both regimens were given every 3 weeks for a maximum of 1 year but discontinued prematurely in the event of progressive disease or severe toxicity . In addition , epirubicin was discontinued at a cumulative dose of 1000 mg/m(2 ) ( 950 mg/m(2 ) from June 1999 ) . Prior anthracycline-based adjuvant chemotherapy and prior chemotherapy for metastatic breast cancer was not allowed . Reported results were all based on intent-to-treat analyses . RESULTS Overall response rates to vinorelbine and epirubicin , and epirubicin alone , were 50 % and 42 % , respectively ( P = .15 ) . The complete response rate was significantly superior in the combination arm ( 17 % v 10 % ; P = .048 ) as was median duration of progression-free survival ( 10.1 months v 8.2 months ; P = .019 ) . Median survival was similar in the two arms ( 19.1 months v 18.0 months ; P = .50 ) . Leukopenia related complications , stomatitis , and peripheral neuropathy were more common in the combination arm . The incidences of cardiotoxicity and constipation were similar in both arms . CONCLUSION Addition of vinorelbine to epirubicin conferred a significant advantage in terms of complete response rate and progression-free survival , but not in terms of survival PURPOSE To determine the impact a change in schedule of paclitaxel administration from once every 3 weeks to frequent administration would have on the pathologic complete response ( pCR ) rate in the breast and lymph nodes for patients with invasive breast cancer treated with primary systemic chemotherapy ( PST ) . PATIENTS AND METHODS Patients with clinical stage I-IIIA breast cancer were r and omly assigned to receive PST of paclitaxel doses administered either weekly ( for a total of 12 doses of paclitaxel ) or once every 3 weeks ( four cycles ) , followed by four cycles of fluorouracil/doxorubicin/cyclophosphamide ( FAC ) in st and ard doses every 3 weeks . Two different doses of paclitaxel were used based on lymph node status defined by ultrasound and fine needle aspiration . Clinical response and extent of residual disease in the breast and lymph nodes was assessed after completion of all chemotherapy . RESULTS A total of 258 patients were r and omly assigned to receive doses of paclitaxel administered either weekly or once every 3 weeks , followed by FAC . Of these 258 patients , 110 patients had histologic lymph node involvement and 148 patients had clinical N0 disease . Weekly paclitaxel followed by FAC was administered to 127 patients and once-every-3-weeks paclitaxel followed by FAC was administered to 131 patients . Clinical response to treatment was similar between groups ( P = .25 ) . Patients receiving weekly paclitaxel had a higher pCR rate ( 28.2 % ) than patients treated with once-every-3-weeks paclitaxel ( 15.7 % ; P = .02 ) , with improved breast conservation rates ( P = .05 ) . CONCLUSION The change in schedule of paclitaxel from once every 3 weeks to a more frequent administration significantly improved the ability to eradicate invasive cancer in the breast and lymph nodes PURPOSE Dose-dense and sequential administration of cytotoxic drugs are current approaches to improve outcomes in patients with early-stage breast cancer . METHODS This phase III study investigated 913 women with untreated operable breast cancer ( T2 - 3 , N0 - 2 , M0 ) r and omly assigned to receive either doxorubicin 50 mg/m2 plus docetaxel 75 mg/m2 every 14 days for four cycles with filgrastim support ( ADOC ) , or doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 every 21 days followed by docetaxel 100 mg/m2 every 21 days for four cycles each ( AC-DOC ) . The primary end point was the incidence of pathologic complete ( invasive and noninvasive ) response ( pCR ) in the breast and axillary nodes . Secondary end points were predictors for pCR , clinical response , rate of breast conservation , and safety . RESULTS A pCR was achieved in 94 patients ( 10.6 % ) , but the likelihood was significantly greater with AC-DOC ( 14.3 % ; n = 63 ) than with ADOC ( 7.0 % ; n = 31 ) ( odds ratio , 2.22 ; 90 % CI , 1.52 to 3.24 ; P < .001 ) . Independent predictors of attaining a pCR included the use of sequential therapy , high tumor grade , and negative hormone receptor status . The response rates detected by palpation and by imaging were significantly higher with AC-DOC ( 85.0 % and 78.6 % , respectively ) than with ADOC ( 75.2 % and 68.6 % , respectively ; both P values < .001 ) . The rate of breast-conserving surgery was 63.4 % for AC-DOC and 58.1 % for ADOC ( P = .05 ) . Predominant grade 3/4 toxicities were leucopenia ( AC-DOC , 74.2 % ; ADOC , 53.7 % ) and neutropenia ( AC-DOC , 66.4 % ; ADOC , 44.7 % ) but were infrequently associated with fever ( AC-DOC , 4.6 % ; ADOC , 3.1 % ) . CONCLUSION Sequential AC-DOC is more effective at inducing pCR than dose-dense ADOC as preoperative treatment for patients with operable breast cancer BACKGROUND Vinorelbine is active and well tolerated against advanced breast cancer but there are no published efficacy studies in early breast cancer . We have therefore carried out a r and omised phase III neoadjuvant trial in operable breast cancer . PATIENTS AND METHODS Patients with > or =3 cm operable breast carcinoma were r and omised to receive either vinorelbine 25 mg/m(2 ) on days 1 and 8 and epirubicin 60 mg/m(2 ) on day 1 , 3 weekly for six cycles ( VE ) or doxorubicin 60 mg/m(2 ) and cyclophosphamide 600 mg/m(2 ) i.v . on day 1 , 3 weekly for six cycles ( AC ) , prior to st and ard local therapy , and adjuvant endocrine therapy as appropriate . RESULTS A total of 451 patients were r and omised . Results for AC and VE , respectively , were : overall clinical response 73 % and 74 % , complete clinical remission 20 % and 24 % , pathological complete remission 12 % and 12 % , mastectomy rate 52 % and 55 % . None of these differences were significant . Dose reduction was required in 8 % for AC and 20 % for VE ( P < 0.001 ) ( GSCF support not used ) . Significantly more grade 3/4 toxicity for nausea , vomiting and alopecia ( despite scalp cooling ) was seen for AC compared with VE but significantly less grade 3/4 thrombophlebitis and neuropathy . CONCLUSIONS Neoadjuvant VE is as effective as AC in early breast cancer and was better tolerated except for thrombophlebitis and neuropathy PURPOSE To compare concomitant and sequential adjuvant chemoradiotherapy regimens in node-positive , operable breast cancer patients . METHODS AND MATERIAL S This was a r and omized , French , multicenter , phase III trial enrolling 638 eligible women with prior breast surgery and positive axillary dissection . Patients in Arm A received 500 mg/m2 5-fluorouracil , 12 mg/m2 mitoxantrone , and 500 mg/m2 cyclophosphamide , with concomitant radiotherapy ( 50 Gy + /- 10 - 20-Gy boost ) . Patients in Arm B received 500 mg/m2 5-fluorouracil , 60 mg/m2 epirubicin , and 500 mg/m2 cyclophosphamide , with subsequent radiotherapy . Chemotherapy was administered on Day 1 every 21 days for 4 cycles . RESULTS Median treatment duration s were 64 and 126 days ( Arms A and B , respectively ) , with no significant difference in overall or disease-free survival . Five-year locoregional relapse-free survival favored patients with conservative surgery ( two thirds of the population ) , with less local and /or regional recurrence in Arm A than in Arm B ( 3 % vs. 9 % ; p = 0.01 ) . Multivariate analysis in this subgroup showed a 2.8-fold increased risk of locoregional recurrence with sequential chemoradiotherapy , independent of other prognostic factors ( p = 0.027 ) . Febrile neutropenia and Grade 3 - 4 leukopenia were significantly more frequent in Arm A. Sub clinical left ventricular ejection fraction events at 1 year were more frequent with concomitant radiotherapy ( p = 0.02 ) . CONCLUSIONS Concomitant radiotherapy with adjuvant fluorouracil , mitoxantrone , and cyclophosphamide has significantly better locoregional control in node-positive breast cancer after conservative surgery and 50 % shorter treatment , albeit with slightly more acute toxicity . With mitoxantrone no longer available for adjuvant breast cancer treatment , alternative concomitant chemoradiotherapy studies are needed PURPOSE Southwest Oncology Group (SWOG)/Intergroup study 9623 was undertaken to compare treatment with an anthracycline-based adjuvant chemotherapy regimen followed by high-dose chemotherapy ( HDC ) with autologous hematopoietic progenitor cell support ( AHPCS ) with a modern dose-dense dose-escalated ( nonst and ard ) regimen including both an anthracycline and a taxane . PATIENTS AND METHODS Participants in this phase III r and omized study had operable breast cancer involving four or more axillary lymph nodes and had completed mastectomy or breast-conserving surgery . Patients were r and omly assigned to receive four cycles of doxorubicin and cyclophosphamide followed by HDC with AHPCS or to receive sequential dose-dense and dose-escalated chemotherapy with doxorubicin , paclitaxel , and cyclophosphamide . The primary end point of this study was disease-free survival ( DFS ) . RESULTS Among 536 eligible patients , there was no significant difference between the two arms for DFS or overall survival ( OS ) . Estimated five-year DFS was 80 % ( 95 % CI , 76 % to 85 % ) for dose-dense therapy and 75 % ( 95 % CI , 69 % to 80 % ) for transplantation . Estimated 5-year OS was 88 % ( 95 % CI , 84 % to 92 % ) for dose-dense therapy and 84 % ( 95 % CI , 79 % to 88 % ) for transplantation . CONCLUSION There is no evidence that transplantation was superior to dose-dense dose-escalated therapy . Transplantation was associated with an increase in toxicity and a possibly inferior outcome , although the hazard ratios were not significantly different from 1 PURPOSE We conducted a phase III r and omized study of two adjuvant treatment schedules of doxorubicin ( A ) and cyclophosphamide ( C ) in early-stage breast cancer to determine if administration of sequential single agents ( A -- > C ) results in superior disease-free survival ( DFS ) and overall survival ( OS ) versus the same total dose given in combination ( AC ) . PATIENTS AND METHODS High-risk node-negative or low-risk node-positive breast cancer patients received AC given : ( arm I ) concurrently ( AC ) doxorubicin 54 mg/m2 and cyclophosphamide 1.2 g/m2 intravenously ( IV ) every 3 weeks for six cycles ; or ( arm II ) in sequence ( A C ) doxorubicin 40.5 mg/m2 IV days 1 and 2 every 3 weeks for four cycles followed by cyclophosphamide 2.4 gm/m2 IV every 2 weeks for three cycles . Total dose and duration were identical , but the intensity of each drug was increased on A C. Both arms included granulocyte colony-stimulating factor support and prophylactic antibiotics .  All but premenopausal women with receptor negative tumors received tamoxifen after chemotherapy . RESULTS Between 1994 and 1997 , 3,176 patients were r and omly assigned . Arms were well balanced ; 48 % of eligible patients were node-negative and 48 % were estrogen receptor-positive . No significant differences in OS or DFS were observed ; 5-year estimates of OS ( 95 % CI ) were 88 % ( 87 % to 90 % ) on AC and 89 % ( 87 % to 91 % ) on A -- > C. Grade 4 hematologic toxicity was greater on A -- > C , but nonhematological grade 4 was similar . CONCLUSION The overall result does not support superiority of dose-intense sequenced single agents . The greater toxicity of higher doses of single agents does not support their sequential use R and om assignment of treatments is an essential feature of experimental design in general and clinical trials in particular . It provides broad comparability of treatment groups and vali date s the use of statistical methods for the analysis of results . Various devices are available for improving the balance of prognostic factors across treatment groups . Several recent initiatives to diminish the role of r and omization are seen as being potentially misleading . R and omization is entirely compatible with medical ethics in circumstances when the treatment of choice is not clearly identified BACKGROUND Docetaxel is more effective than doxorubicin for patients with advanced breast cancer . The Breast International Group 02 - 98 r and omized trial tested the effect of incorporating docetaxel into anthracycline-based adjuvant chemotherapy and compared sequential vs concurrent administration of doxorubicin and docetaxel . METHODS Patients with lymph node-positive breast cancer ( n = 2887 ) were r and omly assigned to one of four treatments : 1 ) sequential control ( four cycles of doxorubicin at 75 mg/m2 , followed by three cycles of cyclophosphamide , methotrexate , and 5-fluorouracil [ CMF ] ) ; 2 ) concurrent control ( four cycles of doxorubicin at 60 mg/m2 plus cyclophosphamide at 600 mg/m2 , followed by three cycles of CMF ) ; 3 ) sequential docetaxel ( three cycles of doxorubicin at 75 mg/m2 , followed by three cycles of docetaxel at 100 mg/m2 , followed by three cycles of CMF ) ; 4 ) concurrent docetaxel ( four cycles of doxorubicin at 50 mg/m2 plus docetaxel at 75 mg/m2 , followed by three cycles of CMF ) . The primary comparison evaluated the efficacy of including docetaxel regardless of schedule and was planned after 1215 disease-free survival ( DFS ) events ( ie , relapse , second primary cancer , or death from any cause ) . Docetaxel and control treatment groups were compared by log-rank tests , and hazard ratios ( HR ) of DFS events were calculated by Cox modeling . All statistical tests were two-sided . RESULTS Due to a lower-than-anticipated rate of relapse , this analysis was performed after 5 years with 732 events . Patients in control arms had a 5-year DFS of 73 % ( 95 % confidence interval [ CI ] = 70 % to 75 % ) . Docetaxel treatment result ed in an improvement in DFS of borderline statistical significance compared with control treatment ( HR = 0.86 , 95 % CI = 0.74 to 1.00 ; P = .05 ) . However , DFS in the sequential docetaxel arm was better than that in the concurrent docetaxel arm ( HR = 0.83 , 95 % CI = 0.69 to 1.00 ) and in the sequential control arm ( HR = 0.79 , 95 % CI = 0.64 to 0.98 ) . CONCLUSIONS Incorporating docetaxel into anthracycline-based therapy result ed in an improvement in DFS that was of borderline statistical significance . However , important differences may be related to doxorubicin and docetaxel scheduling , with sequential but not concurrent administration , appearing to produce better DFS than anthracycline-based chemotherapy PURPOSE This is the first study in which the NK(1)-receptor antagonist , aprepitant ( APR ) , was evaluated for the prevention of chemotherapy-induced nausea and vomiting ( CINV ) with moderately emetogenic chemotherapy . PATIENTS AND METHODS Eligible breast cancer patients were naive to emetogenic chemotherapy and treated with cyclophosphamide + /- doxorubicin or epirubicin .  Patients were r and omly assigned to either an aprepitant regimen ( day 1 , APR 125 mg , ondansetron ( OND ) 8 mg , and dexamethasone 12 mg before chemotherapy and OND 8 mg 8 hours later ; days 2 through 3 , APR 80 qd ) [ DOSAGE ERROR CORRECTED ] or a control regimen ( day 1 , OND 8 mg and dexamethasone 20 mg before chemotherapy and OND 8 mg 8 hours later ; days 2 through 3 , OND 8 mg bid ) . Data on nausea , vomiting , and use of rescue medication were collected with a self-report diary . The primary efficacy end point was the proportion of patients with complete response , defined as no vomiting and no use of rescue therapy , during 120 hours after initiation of chemotherapy in cycle 1 . The secondary end point was the proportion of patients with an average item score higher than 6 of 7 on the Functional Living Index-Emesis question naire . RESULTS Of 866 patients r and omized , 857 patients ( 99 % ) were assessable .  Overall complete response was greater with the aprepitant regimen than with the control regimen ( 50.8 % v 42.5 % ; P = .015 ) . More patients in the aprepitant group reported minimal or no impact of CINV on daily life ( 63.5 % v 55.6 % ; P = .019 ) . Both treatments were generally well tolerated . CONCLUSION The aprepitant regimen was more effective than the control regimen for prevention of CINV in patients receiving both an anthracycline and cyclophosphamide 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 PURPOSE To evaluate whether a relationship exists between docetaxel dose and clinical response in the treatment of patients with advanced breast cancer . PATIENTS AND METHODS Patients whose cancer had progressed after one prior chemotherapy regimen for advanced breast cancer or had recurred during or within 6 months of adjuvant chemotherapy were r and omly assigned to docetaxel 60 , 75 , or 100 mg/m2 intravenously every 3 weeks . RESULTS Five hundred twenty-seven patients were r and omly assigned ( intent to treat [ ITT ] ) , and 524 were assessable for toxicity . In the population assessable for efficacy ( n = 407 ) , logistic regression analysis showed that increasing docetaxel dose was significantly associated with higher response rate ( P = .007 ) and improved time to progression ( TTP ; P = .014 ) . In the ITT analysis , a significant dose-response relationship was observed for tumor response ( P = .026 ) but not for TTP ( P = .067 ) . The incidences of most hematologic and nonhematologic toxicities were related to increasing dose , with grade 3 to 4 neutropenia occurring in 76.4 % , 83.7 % , and 93.4 % and febrile neutropenia occurring in 4.7 % , 7.4 % , and 14.1 % of patients administered the 60 , 75 , and 100 mg/m2 doses , respectively . One death was considered treatment related . CONCLUSION A relationship between increasing dose of docetaxel and increased tumor response was observed across the dose range of 60 to 100 mg/m2 every 3 weeks . Toxicities were related to increasing dose . Depending on the therapy goal , any of the doses studied may be appropriate for second-line treatment of advanced breast cancer We compared the efficacy of CEF ( cyclophosphamide , epirubicin , and fluorouracil ) against CMF ( cyclophosphamide , methotrexate , and fluorouracil ) in moderate or high risk breast cancer patients . We r and omly assigned 1224 patients with completely resected unilateral breast cancer to receive nine cycles of three-weekly intravenous CMF or CEF . Patients were encouraged to take part in a parallel trial comparing oral pamidronate 150 mg twice daily for 4 years versus control ( data not shown ) . Substitution of methotrexate with epirubicin significantly reduced the unadjusted hazard for disease-free survival ( DFS ) by 16 % ( hazard ratio 0.84 ; 95 % CI ; 0.71 - 0.99 ) and for overall survival by 21 % ( hazard ratio 0.79 ; 95 % CI ; 0.66 - 0.94 ) . The risk of secondary leukaemia and congestive heart failure was similar in the two groups . Overall CEF was superior over CMF in terms of DFS and OS  in patients with operable breast cancer without subsequent increase in late toxicities BACKGROUND Lapatinib , a tyrosine kinase inhibitor of human epidermal growth factor receptor type 2 ( HER2 , also referred to as HER2/neu ) and epidermal growth factor receptor ( EGFR ) , is active in combination with capecitabine in women with HER2-positive metastatic breast cancer that has progressed after trastuzumab-based therapy . In this trial , we compared lapatinib plus capecitabine with capecitabine alone in such patients . METHODS Women with HER2-positive , locally advanced or metastatic breast cancer that had progressed after treatment with regimens that included an anthracycline , a taxane , and trastuzumab  were r and omly assigned to receive either combination therapy ( lapatinib at a dose of 1250 mg per day continuously plus capecitabine at a dose of 2000 mg per square meter of body-surface area on days 1 through 14 of a 21-day cycle ) or monotherapy ( capecitabine alone at a dose of 2500 mg per square meter on days 1 through 14 of a 21-day cycle ) . The primary end point was time to progression , based on an evaluation by independent review ers under blinded conditions . RESULTS The interim analysis of time to progression met specified criteria for early reporting on the basis of superiority in the combination-therapy group . The hazard ratio for the independently assessed time to progression was 0.49 ( 95 % confidence interval , 0.34 to 0.71 ; P<0.001 ) , with 49 events in the combination-therapy group and 72 events in the monotherapy group . The median time to progression was 8.4 months in the combination-therapy group as compared with 4.4 months in the monotherapy group . This improvement was achieved without an increase in serious toxic effects or symptomatic cardiac events . CONCLUSIONS Lapatinib plus capecitabine is superior to capecitabine alone in women with HER2-positive advanced breast cancer that has progressed after treatment with regimens that included an anthracycline , a taxane , and trastuzumab . ( Clinical Trials.gov number , NCT00078572 [ Clinical Trials.gov ] . ) PURPOSE Lonidamine ( LND ) can enhance the activity of anthracyclines in patients with metastatic breast cancer . A multicenter , prospect i ve , r and omized trial was design ed to determine whether the association of LND with high-dose epirubicin plus cyclophosphamide ( EC ) could improve disease-free survival ( DFS ) in patients with early breast cancer ( BC ) compared with EC alone . Granulocyte colony-stimulating factor ( G-CSF ) was added to maintain the EC dose-intensity . PATIENTS AND METHODS From October 1991 to April 1994 , 506 patients with stage I/II BC were r and omly assigned to four groups : ( A ) epirubicin 120 mg/m2 and cyclophosphamide 600 mg/m2 administered intravenously on day 1 every 21 days for four cycles ( 124 patients ) ; ( B ) EC plus LND 450 mg/d administered orally ( 125 patients ) ; ( C ) EC plus G-CSF administered subcutaneously ( 129 patients ) ; ( D ) EC plus LND plus G-CSF ( 128 patients ) . RESULTS Median follow-up was 55 months . Five-year DFS rate was similar for LND ( B+D groups ; 69.6 % ) versus non-LND arms ( A+C groups ; 70.3 % ) and G-CSF ( C+D groups ; 67.2 % ) versus non-G-CSF arms ( A+B groups ; 72.9 % ) . Five-year overall survival ( OS ) was comparable in LND ( 79.1 % ) versus non-LND arms ( 81.3 % ) and in G-CSF ( 80.6 % ) versus non-G-CSF arms ( 79.6 % ) . DFS and OS distributions in LND and G-CSF arms did not change according to tumor size , node , receptor , and menopausal status . G-CSF dramatically reduced hematologic toxicity without having a significant impact on dose-intensity ( 98.1 % v 95.5 % for C+D and A+B groups , respectively ) . CONCLUSION EC is active and well tolerated in patients with early breast cancer . The addition of LND or G-CSF does not improve DFS or OS PURPOSE ABI-007 , the first biologically interactive albumin-bound paclitaxel in a nanameter particle , free of solvents , was compared with polyethylated castor oil-based st and ard paclitaxel in patients with metastatic breast cancer ( MBC ) . This phase III study was performed to confirm pre clinical studies demonstrating superior efficacy and reduced toxicity of ABI-007 compared with st and ard paclitaxel . PATIENTS AND METHODS Patients were r and omly assigned to 3-week cycles of either ABI-007 260 mg/m(2 ) intravenously without premedication ( n = 229 ) or st and ard paclitaxel 175 mg/m(2 ) intravenously with premedication ( n = 225 ) . RESULTS ABI-007 demonstrated significantly higher response rates compared with st and ard paclitaxel ( 33 % v 19 % , respectively ; P = .001 ) and significantly longer time to tumor progression ( 23.0 v 16.9 weeks , respectively ; hazard ratio = 0.75 ; P = .006 ) . The incidence of grade 4 neutropenia was significantly lower for ABI-007 compared with st and ard paclitaxel ( 9 % v 22 % , respectively ; P < .001 ) despite a 49 % higher paclitaxel dose . Febrile neutropenia was uncommon ( < 2 % ) , and the incidence did not differ between the two study arms . Grade 3 sensory neuropathy was more common in the ABI-007 arm than in the st and ard paclitaxel arm ( 10 % v 2 % , respectively ; P < .001 ) but was easily managed and improved rapidly ( median , 22 days ) . No hypersensitivity reactions occurred with ABI-007 despite the absence of premedication and shorter administration time . CONCLUSION ABI-007 demonstrated greater efficacy and a favorable safety profile compared with st and ard paclitaxel in this patient population . The improved therapeutic index and elimination of corticosteroid premedication required for solvent-based taxanes make the novel albumin-bound paclitaxel ABI-007 an important advance in the treatment of MBC PURPOSE To compare the clinical and pathologic response rates of doxorubicin and cyclophosphamide ( AC ) with doxorubicin and docetaxel ( AD ) as primary chemotherapy in women with primary or locally advanced breast cancer . PATIENTS AND METHODS Eligible patients with histologically proven breast cancer with primary tumors > /= 3 cm , inflammatory or locally advanced disease , and no evidence of metastases were r and omly assigned to receive a maximum of six cycles of either doxorubicin ( 60 mg/m(2 ) ) plus cyclophosphamide ( 600 mg/m(2 ) ) administered intravenously ( IV ) every 3 weeks or doxorubicin ( 60 mg/m(2 ) ) plus docetaxel ( 75 mg/m(2 ) ) IV every 3 weeks , followed by surgery on completion of chemotherapy . Results A total of 363 patients were r and omly assigned to AC ( n = 180 ) or AD ( n = 183 ) . A complete clinical response was observed in 17 % and 20 % of patients treated with AC and AD , respectively ( P = .42 ) . Overall ( complete and partial ) clinical response rates for AC and AD were 61 % and 70 % , respectively ( P = .06 ) . There was no significant difference in either the pathologic complete response rates in the breast with AC ( 24 % ) and AD ( 21 % ; P = .61 ) or in the number of patients with positive axillary nodes at surgery with AC ( 61 % ) and AD ( 66 % ; P = .28 ) . At a median follow-up of 32 months , there is no significant difference between the two groups for the number of relapses . CONCLUSION In contrast to the positive results reported for sequential docetaxel after AC as primary chemotherapy of breast cancer , our data do not suggest a benefit for simultaneous AD over AC BACKGROUND Among breast cancer patients , nonresponse to initial neoadjuvant chemotherapy is associated with unfavorable outcome . We compared the response of nonresponding patients who continued the same treatment with that of patients who switched to a well-tolerated non-cross-resistant regimen . METHODS Previously untreated breast cancer patients received two 3-week cycles of docetaxel at 75 mg/m(2 ) , doxorubicin at 50 mg/m(2 ) , and cyclophosphamide at 500 mg/m(2 ) per day ( TAC ) . Patients whose tumors did not decrease in size by at least 50 % were r and omly assigned to four additional cycles of TAC or to four cycles of vinorelbine at 25 mg/m(2 ) and capecitabine at 2000 mg/m(2 ) ( NX ) . The outcome was sonographic response , defined as a reduction in the product of the two largest perpendicular diameters by at least 50 % . A difference of 10 % or less in the sonographic response qualified as noninferiority of the NX treatment . Pathological complete response was defined as no invasive or in situ residual tumor masses in the breast and lymph nodes . Toxic effects were assessed . All statistical tests were two-sided . RESULTS Of 2090 patients enrolled in the GeparTrio study , 622 ( 29.8 % ) who did not respond to two initial cycles of TAC were r and omly assigned to an additional four cycles of TAC ( n = 321 ) or to four cycles of NX ( n = 301 ) . Sonographic response rate was 50.5 % for the TAC arm and 51.2 % for the NX arm . The difference of 0.7 % ( 95 % confidence interval = -7.1 % to 8.5 % ) demonstrated noninferiority of NX ( P = .008 ) . Similar numbers of patients in both arms received breast-conserving surgery ( 184 [ 57.3 % ] in the TAC arm vs 180 [ 59.8 % ] in the NX arm ) and had a pathological complete response ( 5.3 % vs 6.0 % ) . Fewer patients in the NX arm than in the TAC arm had hematologic toxic effects , mucositis , infections , and nail changes , but more had h and -foot syndrome and sensory neuropathy . CONCLUSION Pathological complete responses to both regimens were marginal . Among patients who did not respond to the initial neoadjuvant TAC treatment , similar efficacy but better tolerability was observed by switching to NX than continuing with TAC CLINICAL SCENARIO You recall from the first of our 2 articles 1 concerning economic analysis of clinical practice that your chief of medicine has asked you to review relevant economic evidence from the literature and report to the hospital 's pharmacy and therapeutics committee , which is trying to decide on formulary guidelines for the use of streptokinase and tissuetype plasminogen activator ( t-PA ) in the treatment of acute myocardial infa rct ion ( AMI ) . Your literature search identified 2 recent key cost-effectiveness studies : an analysis of economic data collected prospect ively as part of the Global Utilization of  Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries ( GUSTO ) trial 2 of streptokinase vs t-PA by Mark et al , 3 and a decision-analytic model by Kalish et al. 4 In the first article of this 2-part series we showed you how to evaluate the validity of the different economic appraisal study methods . In this article , we A r and omized controlled trial was conducted to evaluate the efficacy of high‐dose chemotherapy ( HDC ) as consolidation of the treatment of high‐risk postoperative breast cancer . Patients under 56 years of age with stage I to IIIB breast cancer involving 10 or more axillary lymph nodes were eligible . The primary endpoint was relapse‐free survival ( RFS ) . Between May 1993 and March 1999 , 97 patients were enrolled , and two patients became ineligible . The median age of the 97 patients was 46 years ( range 27–55 years ) , and 72 ( 74 % ) were premenopausal . The median number of involved axillary nodes was 16 ( range 10–49 ) . All patients had undergone a radical mastectomy . Major characteristics were well balanced between the treatment arms . Forty‐eight patients in the st and ard‐dose ( STD ) arm received six courses of cyclophosphamide , doxorubicin , and 5‐fluorouracil followed by tamoxifen . Forty‐nine patients were assigned to undergo HDC with cyclophosphamide and thiotepa after six courses of cyclophosphamide , doxorubicin , and 5‐fluorouracil followed by tamoxifen ; however , 15 of these patients ( 31 % ) did not undergo HDC . HDC  was well tolerated without any treatment‐related mortality . At a median follow‐up of 63 months , the 5‐year RFS of 47 eligible patients in the STD arm and 48 eligible patients in the HDC arm was 37 % and 52 % on an intent‐to‐treat basis , respectively ( P = 0.17 ) . Five‐year overall survival of all r and omized patients was 62 % for the STD arm and 63 % for the HDC arm ( P = 0.78 ) . Although the prespecified values of the two arms were not so accurate as to allow detection of the observed difference , no advantage of HDC was observed in terms of RFS or overall survival . ( Cancer Sci 2008 ; 99 : 145–151
Background Supportive care interventions can have a substantial impact on side effects of chemotherapy .
Consequently , accurate reporting of such interventions is essential when interpreting clinical trial results .
This study determined the prevalence and quality of reporting of supportive care treatment for common chemotherapy-induced toxicities in phase III , breast cancer chemotherapy trials .