PHASE-II TRIAL OF 5-FLUOROURACIL AND FOLINIC ACID IN THE TREATMENT OFADVANCED BREAST-CANCER

Standard combination chemotherapy for metastatic breast cancer produce s response rates between 30-60% with limited impact on survival. We un dertook a phase II trial to determine the activity of 5 fluorouracil ( 5FU) and folinic acid (FA) in patients with measurable metastatic or r ecurrent breast cancer who had received no prior chemotherapy. Patient s meeting the eligibility criteria received 5FU 370 mg/m(2)/day and FA 200 mg/m(2)/day for 5 days repeated every 28 days, toxicity allowing. Response defined by standard criteria was assessed every 8 weeks and toxicity according to WHO criteria was determined on every course. Thi rty-three patients were entered on trial. Thirty-two patients were eva luable for response and 33 for toxicity. The dose limiting toxicity wa s stomatitis with 7/32, 19/32, and 5/32 patients experiencing grade 1, 2, and 3 toxicity. Grades 1 and 2 diarrhea occurred in 17/32 and 11/3 2 patients respectively. Myelosuppression was not significant. Two com plete and 11 partial responses were observed. The overall response rat e was 41% (95% CI, 24-58%). Responses were seen in soft tissue and vis ceral sites. Patients who had received adjuvant chemotherapy more than 6 months prior to receiving 5FU and FA responded also. Six of 29 pati ents receiving standard combination chemotherapy as second line treatm ent responded subsequently. We concluded: 1) 5FU and FA is an active c ombination in the treatment of breast cancer warranting further evalua tion in combination with other drugs; 2) the dose-limiting toxicity of stomatitis is tolerable; 3) patients receiving 5FU and FA as first li ne therapy can respond to conventional combination chemotherapy as sec ond line treatment.