Concomitant versus sequential administration of epirubicin and paclitaxel as first‐line therapy in metastatic breast carcinoma

Abstract

BACKGROUND The authors performed a randomized trial comprising patients with metastatic breast carcinoma (MBC). They used a noninferiority design to evaluate whether the results of sequential administration of epirubicin and paclitaxel were not markedly worse than the concomitant administration in terms of objective response rates (ORRs). Toxicity profile, quality of life (QOL), and pharmacoeconomic evaluations were evaluated as well. METHODS In the current study, 202 patients with MBC were randomized to receive either the combination of epirubicin at a dose of 90 mg/m2 plus paclitaxel at a dose of 200 mg/m2 for 8 cycles (concomitant arm, n = 108) or epirubicin at a dose of 120 mg/m2 for 4 cycles followed by paclitaxel at a dose of 250 mg/m2 over 3 hours for 4 cycles every 21 days (sequential arm, n = 94). RESULTS The authors rejected the null hypothesis that the sequential treatment is less active than the standard concomitant regimen (ORRs: concomitant = 58.5%, sequential = 57.6%). The median progression‐free and overall survival periods were 11.0 months (95% confidence interval [95% CI], 9.7–12.3) and 20.0 months (95% CI, 17.2–22.6), respectively, in the concomitant arm and 10.8 months (95% CI, 7.9–13.6) and 26 months (95% CI, 18.1–33.8), respectively, in the sequential arm (P = not significant). Patients who received the sequential regimen experienced a higher incidence of Grade 3/4 (according to the World Health Organization grading system) neutropenia (62.2% of courses vs. 50.62%; P = 0.003) and Grade ≥ 2 neuropathy (45.5% vs. 30.4% of patients; P = 0.03), whereas 6 patients who received the concomitant regimen developed Grade II cardiotoxicity according to New York Heart Association criteria. QOL analyses failed to provide clear differences. CONCLUSIONS The sequential administration of epirubicin and paclitaxel at full doses was found to be as active as their association. Therefore, both the sequential and the combined administration were acceptable options. Cancer 2004. © 2004 American Cancer Society.

Usefulness of chemotherapy beyond the second line for metastatic breast cancer: a therapeutic challenge

“…-According to the literature [46][47] survival after CT1 for metastatic disease would be better with a co mbination regimen, although a sequential protocol can also be proposed for the first two lines [48,50]. In our series, the positive impact of polychemotherapy regimens on survival fro m CT3 was only apparent at CT2, probably because the majority of the patients had responded to CT1 using single or mu ltip le drug regimens.…”

Body Mass Index and Prognosis of Metastatic Breast Cancer Patients Receiving First-Line Chemotherapy

“…The methods (including treatment details) and the results of these studies have been reported individually (24)(25)(26). All data had been prospectively collected and had been entered into a centralized patient data management system at the Trial Centers of the National Cancer Research Institute of Genoa, Italy and of the IRST, Meldola (FC), Italy.…”

Risk of Treatment Related Death and Febrile Neutropaenia with First Line Palliative Chemotherapy for De Novo Metastatic Breast Cancer in Clinical Practice in a Middle Resource Country

“…While in the adjuvant setting, clinicians and patients expect a low risk of FN and TRD, in the metastatic setting the expected rates should be higher as patients are either symptomatic or without further treatment can expect to become symptomatic soon and eventually die of metastatic disease. Reported FN rates in the literature from clinical trials for first line chemotherapy in MBC range from 4.9% to as high as 47.8% (Biganzoli et al, 2002;Alba et al, 2004;Conte et al, 2004;Cresta et al, 2004;Park et al, 2010;Tomova et al, 2010, Chan A et al, 2011. These rates differed according to different regimens and were the highest for regimens using combination chemotherapy rather than sequential treatment.…”

“…In fact, combination chemotherapy was shown to have a detrimental effect on progression free survival and increased rates of FN (Dear et al, 2013). The available data on TRD from clinical trials with chemotherapy for MBC range from 0.4% to 5.3% (Baker et al, 1974;Chlebowski et al, 1989;FESG, 2000;Biganzoli et al, 2002;Alba et al, 2004;Conte et al, 2004;Cresta et al, 2004;Park et al, 2010;Tomova et al, 2010, Chan A et al, 2011. Due to the paucity of data regarding the FN and TRD rates for de novo MBC especially in the clinical practice setting where we can expect a higher rate compared to clinical trial setting.…”