Phase II study of continuous infusional 5-fluorouracil with epirubicin and carboplatin (instead of cisplatin) in patients with metastatic/locally advanced breast cancer (infusional ECarboF): a very active and well-tolerated outpatient regimen

Bonnefoi, Hervé; Smith, Ian; O’Brien, Mary; Seymour, Michel; Powles, T. J.; Allum, W. H.; Ebbs, S. R.; Baum, M

doi:10.1038/bjc.1996.67

Cited by 23 publications

(6 citation statements)

References 29 publications

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“…MDR and median OS were 8 and 14 months, respectively. These results are very similar to those previously achieved with the cisplatin-containing combination; however, severe grade III/IV toxicity was low [116]. Oxaliplatin was also used in combination with 5-fluorouracil in a phase II trial in pretreated patients with MBC.…”

Section: Experience With Combination Chemotherapysupporting

confidence: 76%

Platinum-Based Compounds for the Treatment of Metastatic Breast Cancer

Shamseddine¹,

Farhat²

2011

Chemotherapy

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The role of platinum-based compounds (PBCs) in the treatment of metastatic breast cancer (MBC) has been extensively studied. As single agents, high response rates have been observed in first-line therapy, while results in pretreated patients were discouraging. Regimens containing cisplatin/carboplatin together with taxanes showed the highest efficacy and safety as both first-line and second-line therapy. When administered with vinorelbine, the combination was also active and well tolerated in anthracycline- and taxane-pretreated patients. Combining PBCs with etoposide or nucleoside analogues showed moderate activity, yet high toxicity in the case of etoposide. The overall results for the combination with anthracyclines were disappointing. Addition of trastuzumab to PBC combinations showed remarkable activity and good tolerability in patients with HER2/neu overexpression. The use of cisplatin or carboplatin alongside novel targeted therapeutics for patients with triple-negative MBC seems promising and is being further evaluated. The use of PBCs against MBC requires careful patient selection and combination with the right chemotherapeutic agent.

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Section: Experience With Combination Chemotherapysupporting

confidence: 76%

Platinum-Based Compounds for the Treatment of Metastatic Breast Cancer

Shamseddine¹,

Farhat²

2011

Chemotherapy

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“…Similar results have been achieved by the same team with a combination in which carboplatin had been substituted for cisplatin (Bonnefoi et al, 1996). The original ECF regimen was also able to provide an overall response rate of 98% with 66% complete remission in a series of 50 patients with large primary potentially operable breast cancers (Smith et al, 1995).…”

Section: Discussionsupporting

confidence: 59%

Randomized trial comparing protracted infusion of 5-fluorouracil with weekly doxorubicin and cyclophosphamide with a monthly bolus FAC regimen in metastatic breast carcinoma (SPM90)

Pierga

Jouve²,

Asselain³

et al. 1998

Br J Cancer

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Summary Infusional 5-fluorouracil in advanced breast cancer has been associated with improved clinical response rates when compared with conventional bolus therapy. As a first line of chemotherapy in proven metastatic breast carcinoma, 258 women were randomly assigned to receive FAC consisting of 5-fluorouracil (F) 600 mg m-2 intravenously (i.v.) over 1 h on days 1, 2 and 3, doxorubicin (A) 50 were nausea and vomiting (P < 0.01). We conclude that the two regimens appeared equally effective but have different toxicities. Keywords: infusional 5-fluorouracil; metastatic breast cancerThe aim of conventional chemotherapy in clinically disseminated breast cancer is to palliate symptoms and to improve the quality of life. Using conventional chemotherapy regimens in metastatic breast cancer, response rates of 50% to 60% are commonly achieved (Jones et al, 1994). Combination chemotherapy has also been shown to prolong the survival of these patients from first recurrence, although there has not been a significant improvement in long-term survival in the past ten years. Until more effective chemotherapeutic regimens that result in durable remissions are developed, a significant decrease in mortality rate will not be observed (Ross et al, 1985).A correlation between increased dose intensity and better outcome has been described in metastatic disease (Hryniuk et al, 1986). Dose intensity could also be increased by the use of lowdose continuous infusion chemotherapy (Lokich and Anderson, 1995). The response rate to single-agent 5-fluorouracil administered by short infusion was 26% in an overview of 1263 breast cancer patients (Carter, 1976). 5-FU is an S-phase-specific agent with a short serum half-life of 10-20 min owing to rapid catabolism to its metabolites (Fraile et al, 1980), supporting a rationale for continuous infusion over bolus administration. Continuous infusion 5-FU has been used in several phase II studies against solid tumours. Significant activity has been demonstrated against colorectal carcinoma and breast cancer, with response rates Correspondence to: J-Y Pierga ranging from 32% (Hansen et al, 1987) to 53% (Huan et al, 1989). Doses of 300 to 350 mg m-2 day-1 for infusions lasting more than 30 days were achieved in early studies (Lokich et al, 1981). The breast cancer studies included some patients who responded to infusional 5-FU and were previously resistant to bolus therapy (Hansen, 1991). A recent, detailed review of infusional 5-FU in advanced breast cancer has concluded that this administration is associated with superior clinical response rates over conventional bolus therapy (Anderson, 1993).Using a continuous infusion of 5-FU over a twice-monthly, 5-day course (days 1-5 and 15-19) associated with 4-weekly injections of doxorubicin, cyclophosphamide and vindesine on days 2, 5, 16 and 19, we have reported previously an objective response rate of 74% with a complete response rate of 28% in a small series of 48 patients with metastatic breast carcinoma (Jouve et al, 1989).Median response and survival ...

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“…The use of six months of continuous 5-FU infusions combined with Epi and Cis has been studied in a phase II study on 52 patients with metastatic disease and LABC (192). The response rate was 81%, 17% clinical complete responders in metastatic disease and 56% in LABC.…”

Section: Scheduling Of Chemotherapymentioning

confidence: 98%

A Systematic Overview of Chemotherapy Effects in Breast Cancer

Bergh¹,

Jönsson²,

Glimelius³

et al. 2001

Acta Oncologica

150

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A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for the evaluation of the scientific literature are described separately (Acta Oncol 2001; 40: 155-65). This synthesis of the literature on chemotherapy for breast cancer is based on 233 randomised studies, 9 meta-analysis of randomised studies, a population-based cohort study and 18 overviews/retrospective analyses including a total of 155,243 patients. The conclusions reached can be summarised into the following points: Adjuvant treatment-- There is solid scientific support from randomised studies that adjuvant polychemotherapy at 10 years will result in an absolute mortality reduction for patients younger than 50 years by 12% for node positive (34% relative mortality reduction corresponding to an estimated median survival prolongation of several years) and 6% for node negative patients. For women aged 50 to 69 years, the corresponding figures for node positive and node negative patients are 6% and 2%, respectively (approximately 11% relative mortality reduction). Anthracycline-containing combinations result in an absolute survival benefit at five years of 3%, compared with non-anthracycline based polychemotherapy. There are indications that the taxane paclitaxel may further improve the survival compared with anthracyclines. However, the limited data preclude conclusions for the routine care. The addition of tamoxifen to chemotherapy further enhances the survival benefit for receptor positive subgroups. The roles of more dose-intensive regimens, including high-dose therapy with stem cell support, are presently studied in randomised investigations. The data presented so far are conflicting but they do not in general support high-dose therapy. Quality of life, based on analyses of randomised studies, demonstrate that adjuvant polychemotherapy has an initial detrimental effect, but long-term follow-up of treated patients demonstrates no impairment of quality of life compared with untreated patients. Polychemotherapy in standard doses should be offered to premenopausal node positive patients, and the corresponding postmenopausal group with a receptor-negative breast cancer and to node negative patients with high risk factors. Polychemotherapy should be combined with tamoxifen to all patients with receptor-positive tumours. Due to a need of more knowledge in this field, patients should be included in investigational protocols. Locally advanced breast cancer-- Based on current knowledge, treatment of patients with locally advanced breast cancer should include neoadjuvant/preoperative polychemotherapy since there is evidence from controlled studies that such therapy will statistically significantly increase the number of patients who can be offered breast-conserving surgery. Indirect comparisons also demonstrate survival improvements, but the scientific support is equivocal. Metastatic breast cancer-- The median survival for patients with metastatic disea...

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Phase II study of continuous infusional 5-fluorouracil with epirubicin and carboplatin (instead of cisplatin) in patients with metastatic/locally advanced breast cancer (infusional ECarboF): a very active and well-tolerated outpatient regimen

Cited by 23 publications

References 29 publications

Platinum-Based Compounds for the Treatment of Metastatic Breast Cancer

Platinum-Based Compounds for the Treatment of Metastatic Breast Cancer

Randomized trial comparing protracted infusion of 5-fluorouracil with weekly doxorubicin and cyclophosphamide with a monthly bolus FAC regimen in metastatic breast carcinoma (SPM90)

A Systematic Overview of Chemotherapy Effects in Breast Cancer

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