Preop 5-FU May Avoid Mastectomy in High Risk Early Breast Ca

NEW YORK--Women facing mastectomy because of high-risk early breastcancer may benefit from a new strategy that reduces tumor size,allowing conservative surgery or eliminating the need for surgery,Ian E. Smith, MD, said at the symposium of the Chemotherapy Foundation.

Studies conducted at the Royal Marsden Hospital and Instituteof Cancer Research, London, have achieved significant responserates and complete remissions with a regimen of high-intensitypreoperative infusional chemotherapy, said Dr. Smith, head ofthe Section of Medicine at Royal Marsden.

The current tendency to opt for lump-ectomy over mastectomy inmany breast cancer cases does not address the problems of womenwith large tumors. Dr. Smith reported on several pilot studiesof women with poor prognosis, large breast cancers who receivedlong-term infusions of 5-fluorouracil (5-FU) plus conventionalepirubicin and cisplatin (ECF).

The infusional ECF regimen involved 5-FU delivered by ambulatorypump and Hickman line in a continuous, 24-hour infusion of 200mg/m² for 6 months, along with eight 3-week intravenous coursesof 50 mg/m² of epirubicin and 60 mg/m² of cisplatin.

A phase II pilot study treated 50 women with a median age of 44years and median tumor diameter of 6 cm, all of whom were candidatesfor mastectomy. Objective response was observed in 49 women, including33 complete clinical remissions. Only 3 patients required mastectomyafter the trial; 31 had breast conserving surgery, and 15 (amongthe group showing complete remission) received no excisional surgery,proceeding instead to post-treatment radiotherapy.

Dr. Smith reported that treatment was generally well tolerated,with severe grade 3-4 toxicity limited to emesis (20%), leukopenia(2%), and alopecia (28%). The toxicity was similar to that seenwith conventional treatment, he said, even though there was afivefold increase in dose-intensity of 5-FU.

He added that the results, particularly complete response rates,appear to be superior to those achieved with cyclophosphamide/methotrexate/5-FU(CMF) and mitomycin/mitoxantrone/methotrexate (MMM) regimens.On 2-year follow-up, local recurrences developed in 10% of patients,a rate superior to that seen with conventional chemotherapy.

Pathologic assessments bore out this advantage: Tumor cellularitywas markedly reduced or absent in 21 of 26 repeat biopsies, comparedwith 9 of 25 for conventional chemotherapy (81% vs 36%), Dr. Smithsaid.

Aside from the potential for down-staging a tumor before surgery,preopera-tive chemotherapy offers the opportunity to use the primarytumor as an in vivo measure of response. With core needle biopsiesfollowing the first course of treatment, "we can tell ifthat patient's particular tumor is sensitive to the chemotherapybeing used," Dr. Smith noted.

Patients who do not show a response can go on to more aggressivetreatment. Those who do show a response can avoid the major toxicitiesof high-dose chemotherapy and stem cell rescue.

Dr. Smith's group is currently enrolling patients in a phase IIIrandomized trial that will compare 6 courses each of preoperativeinfusional ECF with "gold standard" conventional AC(Adriamycin, 60 mg/m², and cyclophosphamide, 600 mg/m²,IV every 3 weeks).

The trial will seek to determine if there is a large enough differencein outcome to justify the labor-intensive nature of the infusionalapproach, he said.