Adjuvant Capecitabine in Combination With Docetaxel, Epirubicin, and Cyclophosphamide for Early Breast Cancer

Joensuu, Heikki; Kellokumpu‐Lehtinen, Pirkko‐Liisa; Huovinen, Riikka; Jukkola-Vuorinen, Arja; Tanner, Minna; Kokko, R.; Ahlgren, Johan; Auvinen, Päivi; Lahdenperä, Outi; Kosonen, Sanna; Villman, Kenneth; Nyandoto, Paul; Nilsson, Greger; Poikonen‐Saksela, Paula; Kataja, Vesa; Junnila, Jouni; Bono, Petri; Lindman, Henrik

doi:10.1001/jamaoncol.2016.6120

Cited by 77 publications

(57 citation statements)

References 30 publications

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“…Capecitabine is one of the most widely studied drugs in the neoadjuvant and postoperative adjuvant setting of TNBC. Recently, several randomized clinical trials (RCTs) have evaluated the clinical value of combined treatment with capecitabine for TNBC, but the outcomes of these studies were still controversial [ 14 – 22 ]. Seven meta-analyses summarizing the role of capecitabine in breast cancer adjuvant and neoadjuvant chemotherapy have been performed, six of which included all subtypes of patients, not just TNBC patients [ 13 , 23 – 28 ].…”

Section: Introductionmentioning

confidence: 99%

The role of capecitabine-based neoadjuvant and adjuvant chemotherapy in early-stage triple-negative breast cancer: a systematic review and meta-analysis

Huo

Zhao

et al. 2021

BMC Cancer

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Background The role of capecitabine in neoadjuvant and adjuvant chemotherapy for early-stage triple-negative breast cancer (TNBC) is highly controversial. Our meta-analysis was designed to further elucidate the effects of capecitabine on survival in early-stage TNBC patients and its safety. Methods PubMed, Embase, and papers presented at several main conferences were searched up to December 19, 2019, to investigate capecitabine-based versus capecitabine-free neoadjuvant and adjuvant chemotherapy in TNBC patients. Heterogeneity was assessed using I2 test, combined with hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI) computed for disease-free survival (DFS), overall survival (OS), and over grade 3 adverse events (AEs). Results A total of 9 randomized clinical trials and 3842 TNBC patients were included. Overall, the combined capecitabine regimens in neoadjuvant and adjuvant chemotherapy showed significantly improved DFS (HR = 0.75; 95% CI, 0.65–0.86; P < 0.001) and OS (HR = 0.63; 95% CI, 0.53–0.77; P < 0.001). In subgroup analysis, there were improvements in DFS in the groups with addition of capecitabine (HR = 0.64; 95% CI, 0.53–0.78; P < 0.001), adjuvant chemotherapy (HR = 0.73; 95% CI, 0.63–0.85; P < 0.001), and lymph node positivity (HR = 0.62; 95% CI, 0.44–0.86; P = 0.005). Capecitabine regimens were related to higher risks of diarrhea (OR = 2.88, 95% CI 2.23–3.74, P < 0.001), stomatitis (OR = 2.01, 95% CI 1.53–2.64, P < 0.001) and hand–foot syndrome (OR = 8.67, 95% CI 6.70–11.22, P < 0.001). Conclusion This meta-analysis showed that neoadjuvant and adjuvant chemotherapy combined with capecitabine significantly improved both DFS and OS in early-stage TNBC patients with tolerable AEs. There were benefits to DFS in the groups with the addition of capecitabine, adjuvant chemotherapy, and lymph node positivity.

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Section: Introductionmentioning

confidence: 99%

The role of capecitabine-based neoadjuvant and adjuvant chemotherapy in early-stage triple-negative breast cancer: a systematic review and meta-analysis

Huo

Zhao

et al. 2021

BMC Cancer

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“…Trials investigating newer cytotoxic agents for breast cancer have not yet identified any classes that are clearly superior to taxanes and anthracyclines,2, 3, 4 but the optimal dosage and timing of these two drugs is still unclear. Cell biology and cytokinetic modelling suggest that increasing dose intensity (ie, the amount of drug delivered per unit time) 5 could enhance tumour cell kill, reduce tumour regrowth between cycles, and thereby further improve the likelihood of cure 6, 7.…”

Section: Introductionmentioning

confidence: 99%

Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials

Gray¹,

Bradley²,

Braybrooke³

et al. 2019

The Lancet

265

121

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Summary Background Increasing the dose intensity of cytotoxic therapy by shortening the intervals between cycles, or by giving individual drugs sequentially at full dose rather than in lower-dose concurrent treatment schedules, might enhance efficacy. Methods To clarify the relative benefits and risks of dose-intense and standard-schedule chemotherapy in early breast cancer, we did an individual patient-level meta-analysis of trials comparing 2-weekly versus standard 3-weekly schedules, and of trials comparing sequential versus concurrent administration of anthracycline and taxane chemotherapy. The primary outcomes were recurrence and breast cancer mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded dose-intense versus standard-schedule first-event rate ratios (RRs). Findings Individual patient data were provided for 26 of 33 relevant trials identified, comprising 37 298 (93%) of 40 070 women randomised. Most women were aged younger than 70 years and had node-positive disease. Total cytotoxic drug usage was broadly comparable in the two treatment arms; colony-stimulating factor was generally used in the more dose-intense arm. Combining data from all 26 trials, fewer breast cancer recurrences were seen with dose-intense than with standard-schedule chemotherapy (10-year recurrence risk 28·0% vs 31·4%; RR 0·86, 95% CI 0·82–0·89; p<0·0001). 10-year breast cancer mortality was similarly reduced (18·9% vs 21·3%; RR 0·87, 95% CI 0·83–0·92; p<0·0001), as was all-cause mortality (22·1% vs 24·8%; RR 0·87, 95% CI 0·83–0·91; p<0·0001). Death without recurrence was, if anything, lower with dose-intense than with standard-schedule chemotherapy (10-year risk 4·1% vs 4·6%; RR 0·88, 95% CI 0·78–0·99; p=0·034). Recurrence reductions were similar in the seven trials (n=10 004) that compared 2-weekly chemotherapy with the same chemotherapy given 3-weekly (10-year risk 24·0% vs 28·3%; RR 0·83, 95% CI 0·76–0·91; p<0·0001), in the six trials (n=11 028) of sequential versus concurrent anthracycline plus taxane chemotherapy (28·1% vs 31·3%; RR 0·87, 95% CI 0·80–0·94; p=0·0006), and in the six trials (n=6532) testing both shorter intervals and sequential administration (30·4% vs 35·0%; RR 0·82, 95% CI 0·74–0·90; p<0·0001). The proportional reductions in recurrence with dose-intense chemotherapy were similar and highly significant (p<0·0001) in oestrogen receptor (ER)-positive and ER-negative disease and did not differ significantly by other patient or tumour characteristics. Interpretation Increasing the dose intensity of adjuvant chemotherapy by shortening the interval between treatment cycles, or by giving individual drugs sequentially rather than giving the same drugs concurrentl...

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“…The FinXX trial, in which 1,500 women in Finland and Sweden were recruited, compared three cycles of docetaxel followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil (T+CEF) and three cycles of docetaxel plus capecitabine followed by three cycles of cyclophosphamide, epirubicin, and capecitabine (TX+CEX); the results showed no significant overall survival impact. However, subgroup analysis clearly indicated a superior benefit of TX+CEX to T+CEF in triple negative (TN) disease [ 1 ]. In the CREATE-X trial using eight cycles of a regimen with 3-week cycles of 2500 mg/m 2 capecitabine, the capecitabine group showed significant survival advantages in relapse-free survival and overall survival compared with the control arm.…”

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confidence: 99%

Capecitabine for primary breast cancer

2017

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Adjuvant Capecitabine in Combination With Docetaxel, Epirubicin, and Cyclophosphamide for Early Breast Cancer

Abstract: clinicaltrials.gov Identifier: NCT00114816.

Cited by 77 publications

References 30 publications

The role of capecitabine-based neoadjuvant and adjuvant chemotherapy in early-stage triple-negative breast cancer: a systematic review and meta-analysis

The role of capecitabine-based neoadjuvant and adjuvant chemotherapy in early-stage triple-negative breast cancer: a systematic review and meta-analysis

Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials

Capecitabine for primary breast cancer

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