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? Age and adjuvant chemotherapy use after surgery for stage III colon cancer. 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 Time to initiation of adjuvant chemotherapy in patients with rapidly proliferating early breast cancer. Influence of Reported Study Design Characteristics on Intervention Effect Estimates From Randomized, Controlled Trials
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 BACKGROUND R and omized trials have established that 5-fluorouracil-based adjuvant chemotherapy following resection of stage III colon cancer reduces subsequent mortality by as much as 30 % . However , the extent to which adjuvant therapy is used outside the clinical trial setting , particularly among the elderly , is unknown . METHODS A retrospective cohort study utilizing the Surveillance , Epidemiology , and End Results /Medicare-linked data base identified 6262 patients aged 65 years and older with resected stage III colon cancer . The primary outcome was  chemotherapy use within 3 months of surgery , as ascertained from Medicare cl aims . We examined the extent to which age at diagnosis was associated with adjuvant chemotherapy usage , and we adjusted for potential confounding based on differences in other patient characteristics with the use of multiple logistic regression . All P values were two-sided . RESULTS Age at diagnosis was the strongest determinant of  chemotherapy : 78 % of patients aged 65 - 69 years , 74 % of those aged 70 - 74 years , 58 % of those aged 75 - 79 years , 34 % of those aged 80 - 84 years , and 11 % of those aged 85 - 89 years received postoperative chemotherapy .  The age trend remained pronounced after adjustment for potential confounding based on variation in patients ' demographic and clinical characteristics and after exclusion of patients with any evident comorbidity ( all P values < .001 ) . CONCLUSIONS Adjuvant chemotherapy for stage III colon cancer is used extensively , especially for patients under the age of 75 years . However , treatment rates decline dramatically with chronologic age . Because patients in their 70s and even 80s have a reasonable life expectancy , further efforts are needed to ensure that elderly patients have the opportunity to make informed decisions regarding this potentially curative treatment 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 AIM To evaluate the optimal time interval from definitive surgery to commencing chemotherapy in early breast cancer ( EBC ) . PATIENTS AND METHODS The relationship between time to initiation of adjuvant chemotherapy ( TTC ) , calculated in weeks , and disease-free ( DFS ) or overall survival ( OS ) , was assessed in 921 EBC patients with rapidly proliferating tumours ( thymidine labelling index > 3 % or G3 or Ki67 > 20 % ) , r and omised in a phase III clinical trial ( NCT01031030 ) to receive chemotherapy with or without anthracyclines ( epirubicin→cyclophosphamide , methotrexate and fluorouracil ( CMF ) versus CMF→epirubicin versus CMF ) . DFS , OS and 95 % confidence intervals ( 95 % confidence interval ( CI ) ) were calculated by the Kaplan-Meier method . Multivariate Cox analysis was performed in relation with nodal involvement , oestrogen receptor and human epidermal growth factor receptor 2 ( HER2 ) status , Ki67 value , type of adjuvant chemotherapy , menopausal status and tumour size . RESULTS At a median follow-up of 105 months ( range 2 - 188 ) , a prolonged TTC result ed in a significant increase in the risk of relapse : hazard ratio ( HR ) 1.15 ( 95 % CI 1.02 - 1.30 , p=0.019 ) . Using a backward elimination procedure , TTC , tumour size and nodal involvement remained significantly associated with DFS . A time-dependent receiver-operating characteristic ( ROC ) curve analysis was subsequently utilised to evaluate the best cut-off for TTC , identifying 7 weeks as the best threshold for longer OS ( p=0.043 ) : 8-year OS 88 % ( 95 % CI 85 - 90 ) for patients with a TTC < 7 weeks and 78 % ( 95 % CI 68 - 87 ) for the other group . CONCLUSIONS Our results confirm that a shorter TTC may reduce relapses and possibly also improve clinical outcome in patients with highly proliferating EBC Published evidence suggests that aspects of trial design lead to biased intervention effect estimates , but findings from different studies are inconsistent . This study combined data from 7 meta-epidemiologic studies and removed overlaps to derive a final data set of 234 unique meta-analyses containing 1973 trials . Outcome measures were classified as " mortality , " " other objective , " " or subjective , " and Bayesian hierarchical models were used to estimate associations of trial characteristics with average bias and between-trial heterogeneity . Intervention effect estimates seemed to be exaggerated in trials with inadequate or unclear ( vs. adequate ) r and om-sequence generation ( ratio of odds ratios , 0.89 [ 95 % credible interval { CrI } , 0.82 to 0.96 ] ) and with inadequate or unclear ( vs. adequate ) allocation concealment ( ratio of odds ratios , 0.93 [ CrI , 0.87 to 0.99 ] ) . Lack of or unclear double-blinding ( vs. double-blinding ) was associated with an average of 13 % exaggeration of intervention effects ( ratio of odds ratios , 0.87 [ CrI , 0.79 to 0.96 ] ) , and between-trial heterogeneity was increased for such studies ( SD increase in heterogeneity , 0.14 [ CrI , 0.02 to 0.30 ] ) . For each characteristic , average bias and increases in between-trial heterogeneity were driven primarily by trials with subjective outcomes , with little evidence of bias in trials with objective and mortality outcomes . This study is limited by incomplete trial reporting , and findings may be confounded by other study design characteristics . Bias associated with study design characteristics may lead to exaggeration of intervention effect estimates and increases in between-trial heterogeneity in trials reporting subjectively assessed outcomes
Background It is known that adjuvant chemotherapy improves survival in women with breast cancer .
It is not known whether the interval between surgery and the initiation of chemotherapy influences its effectiveness .
Purpose To determine the relationship between time to initiation of adjuvant chemotherapy and survival in women with breast cancer , through a systematic review of the literature and meta- analysis .