Continuous infusional chemotherapy for early breast cancer: the Royal Marsden Hospital experience

5-FU is a cycle-specific S-phase-dependent drug with a short half life of 10-20 min. There is therefore a rationale for its use in long-term continuous infusional therapy, with doses of up to 300 mg/m2 per day proving feasible for prolonged periods. The schedule is active in patients with heavily pre-treated breast cancer, with responses in up to 53% (overall 29%). At the Royal Marsden Hospital we have evaluated infusional 5-FU 200 mg/m2 per day for up to 6 months in combination with 3-weekly bolus epirubicin (E) 60 mg/m2 and cisplatin (C) 60 mg/m2 (infusional ECF) as pre-operative/neo-adjuvant treatment in 123 patients with operable breast cancer greater than 3 cm (median 6 cm), initially in a phase II study of 50 patients and subsequently as part of a randomised phase III trial. One hundred and eighteen (96%) have achieved objective tumour responses, with 67 (57%) achieving CR. The 5-year actuarial survival rate is 78% and the local recurrence rate without associated metastatic disease 12%. The pathological complete remission (CR) rate was 16%, with a further 5% having residual DCIS only. Pathological CR but not clinical CR is an independent predictor for disease-fee survival. The Royal Marsden is now conducting two multicentre randomised trials of infusional ECF: (i) versus conventional AC (adriamycin cyclophosphamide) as pre-operative/neo-adjuvant chemotherapy, with 376 patients so far randomised towards a target of 400; and (ii), more recently, a similar adjuvant trial versus conventional FEC (5-FU, epirubicin, cyclophosphamide), with 168 patients so far randomised. These trials will determine whether encouraging phase II activity with continuous infusional chemotherapy translates eventually into real survival benefit for patients with early breast cancer.