Looking back from 2015

C Macmillan Press Dose-intense weekly cyclophosphamide, methotrexate, 5-fluorouracil, vincristine and prednisolone (CMFP) in advanced breast cancer Summary Weekly chemotherapy with cyclophosphamide 80mgm-2 day-' p.o. continuously, methotrexate 35 mg m2 week-' i.v., 5-fluorouracil 500 mg m2 weekl' i.v., vincristine 1.4 mg m-i.v. every two weeks and prednisolone 20mg m2 day-' p.o. continuously (CMFVP) was prospectively studied in 45 previously untreated outpatients with advanced breast cancer to determine the feasibility of delivering a dose-intense regimen. Of 40 evaluable patients, complete response (CR) occurred in one patient, partial response (PR) in 20 (CR + PR 53%), stable in eight, progression in 11 and five were unevaluable for response. The median relapse-free survival for responders was 25 weeks and median survival for all patients was 31 weeks. The mean dose intensity relative to the Cooper regimen fell from 1.02 to 0.6 within the first 4 weeks of treatment and the median dose intensity achieved for all patients on study was only 0.52. Eighty-seven per cent of patients had treatment delays with a mean of 3.9 delays per patient and 71% had dose reductions. Neutropenia was the major toxicity with WHO grade 3 or 4 neutropenia (<1.0 x 10 1'-) in 62% of patients and three septic deaths while neutropenic. Dose-intense weekly CMFVP in this schedule cannot be delivered to previously untreated outpatients with advanced breast cancer. Chemotherapy for advanced breast cancer using the combination cyclophosphamide, methotrexate, 5-fluorouracil + prednisolone CMF(P) given in a conventional intermittent schedule produces objective responses in approximately 50% of patients, with a response duration of 9 months (Smalley et al., 1983; Tormey et al., 1982). More recently attention has been directed towards the dose and schedule of therapy as a method of improving results with CMF in this disease. The Cooper regimen, which included vincristine (CMFVP) and used a weekly schedule, appeared to be well tolerated with high responses in advanced disease and satisfactory results as adjuvant chemotherapy (Cooper, 1969; Cooper et al., 1979). Hryniuk and Bush (1984) have studied the dose intensity of C, M and F in published data by converting each dose of drug to mg m-2 week-1 and comparing it directly to the Cooper regimen. They have concluded that many reported CMF programmes deliver much less intense chemo-therapy than Cooper described and that a dose-response relationship may exist for C, M and F, especially if actual doses delivered are studied. Hrynuik and Bush's review was retrospective …