Phase II study of continuous infusion fluorouracil with epirubicin and cisplatin in patients with metastatic and locally advanced breast cancer: an active new regimen.

Jones, Alison; Smith, Ian; O’Brien, Mary; Talbot, Denis; Walsh, Geraldine; Ramage, F.; Robertshaw, H.; Ashley, S.

doi:10.1200/jco.1994.12.6.1259

Cited by 74 publications

(46 citation statements)

References 26 publications

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“…It was found to be active with 64% of patients having a CR or PR. This is a lower response rate than that found with ECF (Jones et al, 1994). However, the confidence intervals for the ETF study were wide (47 -77%), and therefore it cannot be directly compared to the ECF data, and the number of patients in both studies was small.…”

Section: Discussionmentioning

confidence: 66%

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Phase II study of docetaxel in combination with epirubicin and protracted venous infusion 5-fluorouracil (ETF) in patients with recurrent or metastatic breast cancer. A Yorkshire breast cancer research group study

et al. 2004

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This study was originally designed as a phase I/II study, with a dose escalation of docetaxel in combination with epirubicin 50 mg m À2 and 5-fluorouracil (5-FU) 200 mg m À2 day À1 . However, as dose escalation was not possible, the study is reported as a phase II study of the combination to assess response and toxicity. A total of 51 patients with locally advanced or metastatic breast cancer were treated on this phase II study, with doses of docetaxel 50 mg m À2 , epirubicin 50 mg m À2 and infusional 5-FU 200 mg m À2 day À1 for 21 days. The main toxicity of this combination was neutropenia with 89% of patients having grade 3 and 4 neutropenia, and 39% of patients experiencing febrile neutropenia. Nonhaematological toxicity was mild. The overall response rate in the assessable patients was 64%, with median progression-free survival of 38 weeks, and median survival of 70 weeks. The ETF regimen was found to be toxic, and it was not possible to escalate the dose of docetaxel above the first dose level. This regimen has therefore not been taken any further, but as a development of this a new study is ongoing, combining 3-weekly epirubicin, weekly docetaxel and capecitabine, days 1 -14. The treatment of metastatic or advanced breast cancer has evolved over the last few years, and in the 1990s this was largely due to the introduction of the taxane family of drugs. Docetaxel (taxotere) is a semisynthetic taxane derived from 10-deacetyl baccatin III, a precursor isolated from the needles of Taxus baccata. As with the other taxane compounds, it acts by promoting microtubule assembly and inhibiting microtubule depolymerisation. This blocks cells in M phase and so prevents cell division.Docetaxel has well-documented activity in advanced breast cancer with a single agent dose of 100 mg m À2 . The dose-limiting toxicity of docetaxel is grade 3 and 4 neutropenia. The response rate ranges from 19 -57% in pretreated patients and 54 -67% in those with minimal pretreatment (Clemons et al, 1997).Following the single-agent studies, docetaxel was combined with other active agents. The most attractive combination, initially, was with anthracyclines, as docetaxel is known to have activity in anthracycline-resistant disease (Miller et al, 2001). Studies were carried out using epirubicin and docetaxel. For example, docetaxel was escalated with a fixed dose of epirubicin (Venturini et al, 2001). It was found that the dose-limiting toxicity was neutropenia, which was ameliorated to some extent by G-CSF. Other side effects were mild. There were however two toxic deaths. The recommended doses for further investigation were epirubicin 75 mg m À2 and docetaxel 80 mg m À2 . In a further study (Viens et al, 2001), escalating doses of epirubicin were given with a fixed dose of docetaxel 75 mg m À2 . Dose-limiting toxicities were grade 3 and 4 asthenia, febrile neutropenia and stomatitis and diarrhoea. There was an overall response rate of 69.4%, and a median duration of response of 7.8 months. The recommended dose was epirubicin 100 mg m À2 with...

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Section: Discussionmentioning

confidence: 66%

“…A phase II study of eight courses of ECF in 43 patients with metastatic and locally advanced breast cancer (Jones et al, 1994) gave an overall response rate of 84%. This regimen has also been used in a phase II study in patients with large but operable breast cancer in the neoadjuvant setting (Smith et al, 1995).…”

mentioning

confidence: 99%

Phase II study of docetaxel in combination with epirubicin and protracted venous infusion 5-fluorouracil (ETF) in patients with recurrent or metastatic breast cancer. A Yorkshire breast cancer research group study

et al. 2004

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“…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.…”

Section: Abstract: Infusional 5-fluorouracil; Metastatic Breast Cancermentioning

confidence: 99%

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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“…PMT consisted of epirubicin, cisplatin and protracted infusional 5-fluorouracil (ECisF) as previously described (Jones et al, 1994;Smith et al, 1995), for 6-8 cycles of 21 days. In brief, this regimen comprises epirubicin 50-60 mg m-2 and cisplatin 60 mg m-2 on day 1, with continuous ambulatory venous infusion of 5-fluorouracil 200 mg m-2 per 24 h throughout the cycle (days 1-21).…”

Section: Treatment and Assessment Protocolmentioning

confidence: 99%

“…A total of 52 patients were studied; all had invasive breast cancer, confirmed by core biopsy, with initial size > 4 cm by palpation, T2-3, NO-1, MO. PMT was with epirubicin, cisplatin and continuous infusional 5-fluorouracil, as previously described (Jones et al, 1994, J Clin Oncol 12: 1259-1265. Independent clinical and US assessments were made during PMT before surgery or biopsy.…”

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confidence: 99%

Ultrasound assessment of residual abnormalities following primary chemotherapy for breast cancer

Seymour

Moskovic²,

Walsh³

et al. 1997

Br J Cancer

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Summary The purpose of this study was to assess the usefulness of ultrasonography (US) in the assessment of the breast following primary medical therapy (PMT) of large operable breast cancer. A total of 52 patients were studied; all had invasive breast cancer, confirmed by core biopsy, with initial size > 4 cm by palpation, T2-3, NO-1, MO. PMT was with epirubicin, cisplatin and continuous infusional 5-fluorouracil, as previously described (Jones et al, 1994, J Clin Oncol 12: 1259-1265. Independent clinical and US assessments were made during PMT before surgery or biopsy. A total of 31 (60%) patients achieved complete clinical response (cCR), but in only five of these was the posttreatment ultrasound normal. Post-treatment sonographic findings of diffuse parenchymal distortion or a mass lesion without Doppler signal were associated with more favourable histology (pathological CR, non-invasive or microinvasive carcinoma), whereas a mass with Doppler positivity was more often associated with residual macroscopic invasive carcinoma. Patients who did not achieve cCR had a high incidence of residual macroscopic carcinoma (71 %) regardless of the sonographic characteristics. With median follow-up of 27 months (range 12-43), ten (19%) patients have relapsed and six (12%) have died, but only one relapse has occurred within treated breast. Ultrasonography is a sensitive technique for assessing the response to PMT, particularly in patients who achieve cCR. It may be helpful in selecting those patients who do not require post-PMT surgery and in localizing abnormalities in those who do, particularly in those with cCR. However, clinicians should be aware that a residual US abnormality is by no means pathognomonic of residual cancer.

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Phase II study of continuous infusion fluorouracil with epirubicin and cisplatin in patients with metastatic and locally advanced breast cancer: an active new regimen.

Abstract: Infusional ECF is a highly active regimen in advanced breast cancer and warrants evaluation in high-risk early breast cancer.

Cited by 74 publications

References 26 publications

Phase II study of docetaxel in combination with epirubicin and protracted venous infusion 5-fluorouracil (ETF) in patients with recurrent or metastatic breast cancer. A Yorkshire breast cancer research group study

Phase II study of docetaxel in combination with epirubicin and protracted venous infusion 5-fluorouracil (ETF) in patients with recurrent or metastatic breast cancer. A Yorkshire breast cancer research group study

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

Ultrasound assessment of residual abnormalities following primary chemotherapy for breast cancer

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