Improved outcomes from adding sequential Paclitaxel but not from escalating Doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. Benefit of a high-dose epirubicin regimen in adjuvant chemotherapy for node-positive breast cancer patients with poor prognostic factors: 5-year follow-up results of French Adjuvant Study Group 05 randomized trial. Randomized trial of intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer. National Cancer Institute of Canada Clinical Trials Group. Does timing of adjuvant chemotherapy influence the prognosis after early breast cancer? Results of the Danish Breast Cancer Cooperative Group (DBCG) Does timing of adjuvant chemotherapy for early breast cancer influence survival? Impact of Administration‐Related Factors on Outcome of Adjuvant Chemotherapy for Primary Breast Cancer Effect of timing of initiation of adjuvant chemotherapy on disease-free survival in breast cancer Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer: the results of 20 years of follow-up.
PURPOSE This study was design ed to determine whether increasing the dose of doxorubicin in or adding paclitaxel to a st and ard adjuvant chemotherapy regimen for breast cancer patients would prolong time to recurrence and survival . PATIENTS AND METHODS After surgical treatment , 3,121 women with operable breast cancer and involved lymph nodes were r and omly assigned to receive a combination of cyclophosphamide ( C ) , 600 mg/m(2 ) , with one of three doses of doxorubicin ( A ) , 60 , 75 , or 90 mg/m(2 ) , for four cycles followed by either no further therapy or four cycles of paclitaxel at 175 mg/m(2 ) . Tamoxifen was given to 94 % of patients with hormone receptor-positive tumors . RESULTS There was no evidence of a  doxorubicin dose effect . At 5 years , disease-free survival was 69 % , 66 % , and 67 % for patients r and omly assigned to 60 , 75 , and 90 mg/m(2 ) , respectively . The hazard reductions from adding paclitaxel to CA were 17 % for recurrence ( adjusted Wald chi(2 ) P = .0023 ; unadjusted Wilcoxon P = .0011 ) and 18 % for death ( adjusted P = .0064 ; unadjusted P = .0098 ) . At 5 years , the disease-free survival ( + /- SE ) was 65 % ( + /- 1 ) and 70 % ( + /- 1 ) , and overall survival was 77 % ( + /- 1 ) and 80 % ( + /- 1 ) after CA alone or CA plus paclitaxel , respectively . The effects of adding paclitaxel were not significantly different in subsets defined by the protocol , but in an unplanned subset analysis , the hazard ratio of CA plus paclitaxel versus CA alone was 0.72 ( 95 % confidence interval , 0.59 to 0.86 ) for those with estrogen receptor-negative tumors and only 0.91 ( 95 % confidence interval , 0.78 to 1.07 ) for patients with estrogen receptor-positive tumors , almost all of whom received adjuvant tamoxifen . The additional toxicity from adding four cycles of paclitaxel was generally modest . CONCLUSION The addition of four cycles of paclitaxel after the completion of a st and ard course of CA improves the disease-free and overall survival of patients with early breast cancer PURPOSE To determine the influence of the epirubicin dose in operable node-positive breast cancer patients with factors of poor prognosis . PATIENTS AND METHODS Between April 1990 and July 1993 , 565 operable breast cancer patients with either more than three positive nodes or between one and three positive nodes with Scarff Bloom Richardson grade > or = 2 and hormone receptor negativity were r and omized after surgery to receive either fluorouracil 500 mg/m(2 ) , epirubicin 50 mg/m(2 ) , and cyclophosphamide 500 mg/m(2 ) every 21 days for six cycles ( FEC 50 ) or the same regimen except with epirubicin dose of 100 mg/m(2 ) ( FEC 100 ) . Postmenopausal patients received tamoxifen 30 mg/d for 3 years at the beginning of chemotherapy . Radiotherapy was delivered at the end of chemotherapy in both groups . RESULTS The median follow-up was 67 months . The 5-year disease-free survival ( DFS ) was 54.8 % with FEC 50 and 66.3 % with FEC 100 ( P = .03 ) . The 5-year overall survival ( OS ) was 65.3 % and 77.4 % , respectively ( P = .007 ) . The mean relative dose-intensity was similar in the two groups ( 90.3 % and 86.1 % , respectively ) . Neutropenia and anemia were significantly more frequent in FEC 100 ( P < 10(-3 ) ) , as were nausea-vomiting ( P = .008 ) and stomatitis and alopecia ( P < 10(-3 ) ) . Nine cases of grade 3 infection occurred only with FEC 100 , and no toxic deaths occurred . Three cases of acute cardiac toxicity were observed ( FEC50 = 1 , FEC100 = 2 ) and 10 patients ( FEC50 = 6 , FEC100 = 4 ) presented delayed cardiac dysfunctions . Two cases of secondary leukemia were observed ( acute lymphatic leukemia with FEC 50 and acute myelogenous leukemia with FEC 100 ) . CONCLUSION After 5 years of follow-up , the increased epirubicin dose led to a significant benefit in terms of DFS and OS , with a high survival rate among patients with poor-prognosis breast cancer PURPOSE To determine the relative efficacy of an intensive cyclophosphamide , epirubicin , and fluorouracil ( CEF ) adjuvant chemotherapy regimen compared with cyclophosphamide , methotrexate , and fluorouracil ( CMF ) in node-positive breast cancer . PATIENTS AND METHODS Premenopausal women with node-positive breast cancer were r and omly allocated to receive either cyclophosphamide 100 mg/m2 orally days 1 through 14 ; methotrexate 40 mg/m2 intravenously ( i.v . ) days 1 and 8 ; and fluorouracil 600 mg/m2 i.v . days 1 and 8 or cyclophosphomide 75 mg/m2 orally days 1 through 14 ; epirubicin 60 mg/m2 i.v . days 1 and 8 ; and fluorouracil 500 mg/m2 i.v . days 1 and 8 . Each cycle was administered monthly for 6 months . Patients administered CEF received antibiotic prophylaxis with cotrimoxazole two tablets twice a day for the duration of chemotherapy . RESULTS The median follow-up was 59 months . One hundred sixty-nine of the 359  CMF patients developed recurrence compared with 132 of the 351 CEF patients . The corresponding 5-year relapse-free survival rates were 53 % and 63 % , respectively ( P = .009 ) . One hundred seven CMF patients died compared with 85 CEF patients . The corresponding 5-year actuarial survival rates were 70 % and 77 % , respectively ( P = .03 ) . The rate of hospitalization for febrile neutropenia was 1.1 % in the CMF group compared with 8.5 % in the CEF group . There was one case of congestive heart failure in a patient who received CMF compared with none in the CEF group . Acute leukemia occurred in five patients in the CEF group . CONCLUSION The results of this trial show the superiority of CEF over CMF in terms of both disease-free and overall survival in premenopausal women with axillary node-positive breast cancer The purpose of this study was to examine the effect on survival of delaying the start of adjuvant chemotherapy for early breast cancer for up to 3 months after surgery . In the nation-wide clinical trials of the Danish Breast Cancer Cooperative Group , 7501 breast cancer patients received chemotherapy within 3 months of surgery between 1977 and 1999 : 352 with classical cyclofosfamide , metotrexate and 5-fluorouracil ( CMF ) ; 6065 with CMF i.v . and 1084 with cyclofosfamide , epirubicin and 5-fluorouracil . For the analysis , the time between surgery and the start of chemotherapy was divided into four strata ( 1–3 , 4 , 5 and 6–13 weeks ) . The results show that within the three groups of chemotherapy , there was an even distribution of known prognostic factors across the four strata of initiation of chemotherapy . There was no pattern indicating a benefit from early start of chemotherapy . No significant interactions were found for subgroups of patients with a poorer prognosis ( many involved lymph nodes , high- grade malignancies or hormone receptor negative disease ) . In conclusion , we have found no evidence for a survival benefit due to early initiation of adjuvant chemotherapy within the first 2–3 months after surgery PURPOSE Theoretically , patients with early breast cancer might benefit from starting adjuvant chemotherapy soon after surgery , and this would have important clinical implication s. We have addressed this question from a large , single-center data base in which the majority of patients received anthracyclines . PATIENTS AND METHODS A total of 1161 patients from a prospect ively maintained data base treated with adjuvant chemotherapy for early breast cancer at the Royal Marsden Hospital ( London , United Kingdom ) , including 686 ( 59 % ) receiving anthracyclines , were retrospectively analyzed . The disease-free survival ( DFS ) and overall survival ( OS ) of the 368 patients starting chemotherapy within 21 days of surgery ( group A ) were compared with those of the 793 patients commencing chemotherapy > or= 21 days after surgery ( group B ) . Median follow-up time was 39 months ( range , 12 to 147 months ) . RESULTS No significant difference in 5-year DFS was found between the two groups overall ( 70 % for group A v 72 % for group B ; P = .4 ) or in any subgroup . Likewise , there was no difference in 5-year OS ( 82 % for group A v 84 % for group B ; P = .2 ) or when the interval to the start of chemotherapy was considered as a continuous variable ( P = .4 ) . CONCLUSION We have been unable to identify any significant survival benefit from starting adjuvant chemotherapy early after surgery , either overall or in any subset of patients The  survival of 229 patients treated with adjuvant i.v . cyclophosphamide , methotrexate , and 5-fluorouracil ( CMF ) after surgery for primary breast cancer was analyzed according to three administration-related factors : total number of cycles received , time elapsed between surgery and start of chemotherapy , and dose intensity of treatment . All parameters were found to be significantly associated with survival of patients in a univariate analysis . Multivariate analysis confirmed the independent prognostic importance of dose intensity and time between surgery and chemotherapy .  Although prospect i ve studies are needed to confirm such results , clinicians should be aware that unnecessary treatment delays or dose reductions in adjuvant chemotherapy for breast cancer are probably detrimental to patient survival Summary Four hundred and sixty patients with stage II or III breast cancer following regional therapy  were treated with an adjuvant combination chemotherapy consisting of fluorouracil , doxorubicin , and cyclophosphamide ( FAC ) . The relationship between the length of disease-free survival and length of delays in initiation of chemotherapy after surgery was evaluated . Patients were divided into four subgroups according to the length of delay in initiation of chemotherapy  ( < 10 weeks , 10–13 , 14–17 , and ≥ 18 weeks ) . Overall four year diseasefree survival was 64 % , 68 % , 60 % , and 63 % for patient groups with delays of < 10 weeks , 10–13 , 14–17 , or ≥ 18 weeks respectively ( p = 0.39 ) . There was no trend for longer delay in treatment to be associated with shorter disease-free survival , except in poor prognosis patients BACKGROUND Adjuvant combination chemotherapy with cyclophosphamide , methotrexate , and fluorouracil was administered after radical mastectomy for primary breast cancer with histologically positive axillary lymph nodes to assess whether it would improve treatment outcome as compared with surgery alone . Here we report a 20-year follow-up of this investigation . METHODS In 1973 we began a trial involving 386 women who were r and omly assigned to receive either no further treatment after radical mastectomy ( 179 women ) or 12 monthly cycles of adjuvant combination chemotherapy ( 207 women ) . All patients were admitted to the Istituto Nazionale Tumori in Milan , Italy .  Adjuvant chemotherapy was delivered in the outpatient clinic of the Division of Medical Oncology . RESULTS After a median follow-up of 19.4 years , the patients given adjuvant combination chemotherapy had significantly better rates of relapse-free survival ( unadjusted relative risk of relapse , 0.71 ; 95 percent confidence interval , 0.56 to 0.90 ; P = 0.004 ; adjusted relative risk , 0.65 , 95 percent confidence interval , 0.51 to 0.83 ; P < 0.001 ) and total survival ( unadjusted relative risk of death , 0.78 ; 95 percent confidence interval , 0.62 to 0.99 ; P = 0.04 ; adjusted relative risk , 0.76 ; 95 percent confidence interval , 0.60 to 0.97 ; P = 0.03 ) . With the exception of postmenopausal women , a benefit from adjuvant chemotherapy was evident in all subgroups of patients . CONCLUSIONS The long-term results of this trial of adjuvant combination chemotherapy confirm our preliminary observations of the effectiveness of the treatment in women with node-positive breast cancer
Background Adjuvant chemotherapy ( AC ) improves survival among patients with operable breast cancer .
However , the effect of delay in AC initiation on survival is unclear .
We performed a systematic review and meta- analysis to determine the relationship between time to AC and survival outcomes .