Drug scheduling alterations can improve the therapeutic index of both 5-fluorouracil and anthracyclines. We investigated a regimen of weekly doxorubicin and continuous infusional 5-fluorouracil (AcF) in loco-regionally recurrent and metastatic breast cancer. The aims of this phase II study were to use low-dose weekly anthracyclines in a patient group where liver metastases are a frequent problem, to optimise scheduling of 5-fluorouracil using continuous infusion and to conserve alkylating agent use for late intensification in responding patients. Fifty-six patients received 5-fluorouracil 200 mg m-2 day-1 and doxorubicin 20-30 mg m-2 week-1 for at least 6 weeks. Sixty-two percent were chemonaive. Patients were evaluated for dose intensity, response, toxicity and survival. Of the assessable patients, 76% achieved UICC response criteria (20% complete response, 56% partial response). WHO grade 3+ toxicities were: alopecia, 98%; mucositis, 62%; neutropenia, 22%; and grade 3 palmar-plantar syndrome, 24%. Median survival was 13 months, with visceral metastasis conferring a significantly worse outcome (P = 0.03). Grade 3+ mucositis was more frequent with planned doxorubicin dose intensity > or = 25 mg m-2 week-1 (P = 0.04). AcF is highly active in breast cancer with acceptable toxicities and can be used before alkylating agent-based high-dose therapy.

Background:We have previously shown that 5-fluorouracil (5-FU) given by continuous infusion is well tolerated and active in the treatment of breast cancer [1,2].We found that given infusional 5-FU could produce responses in patients whose disease was resistant to bolus 5-FU and speculated that it could be combined safely with methotrexate/cyclophosphamide in a manner analogous to i.v.CMF bolus.Using a modification of the i.v.CMF regimen, comprising a standard dosage of bolus cyclophosphamide at 750 mg/m 2 and bolus methotrexate at 50 mg/m 2 given every 3 weeks we altered the continuously infused 5-FU schedule to 200 mg/m 2 /24 hours and treated 28 patients of whom 23 had had previous chemotherapy (18 containing anthracycline, 4 bolus CMF and 19 infusional 5-FU alone or in combination with other drugs) and 4 post menopausal patients with locally advanced breast cancer.Results: Fourteen responded (2 CR, 12 PR) out of 27 evaluable patients with onset of response between 3 and 9 weeks.Toxicity was relatively mild in the 28 evaluable patients and did not require cessation of treatment, with one exception (vomiting leading to dehydration at home and moderate transient uraemia).The main toxicities seen were WHO grade 3 neutropenia in 13/28 patients and grade 2 mucositis in 2 further patients.Grade 2 palmar/planter syndrome was reported in 4/28 patients and grade 2 or 3 nausea/vomiting was reported in 7/28 patients.Conclusion: This well tolerated regimen is clearly active in patients with heavily pretreated breast cancer and should be tested against intravenous or classical CMF in a randomised trial.

Admissions to 166 American Veterans Administration Hospitals for duodenal ulcer, bleeding duodenal ulcer, perforated duodenal ulcer, essential hypertension (control diagnosis), and all diseases were counted as to calendar month of occurrence over a 6-year period. Duodenal ulcer admissions were less frequent in June, July, and August. Perforated duodenal ulcer was, in addition, less frequent in January. These deficits contrasted sharply with admissions for control categories. Summer deficits are more characteristic of duodenal ulcer than spring and fall peaks. Regional data in this study did not support the possibility that the summer deficit is related to hot weather. Perforations vary with time under more influences than nonperforated duodenal ulcer.