Phase I - II study of oral idarubicin, tegafur and levo-folinate in patients with pretreated advanced breast cancer.

Thirty patients with pretreated advanced breast cancer were enrolled in a study aimed to establish the maximum tolerated dose and to evaluate the efficacy of oral idarubicin (12 mg/m2/day for 3 days every 4 weeks) with tegafur and levo-folinate (200 mg/m2/day and 50 mg/day, respectively, for a minimum of 6 days, increasing the dose and duration according to a modified Fibonacci scheme). The maximum tolerated doses identified were 200 mg/m2 days 1-30 for tegafur and 50 mg days 1-30 for levo-folinate. We obtained 2 partial remissions (7%) and 12 stable disease (45%) in 27 objectively evaluable patients. The main toxicity was gastrointestinal, with no hematologic toxicity. Median time to progression was 4 months (range 2-14), median survival was 10 months (3-30). A median number of 4 cycles (1-13) was administered. The results seem to support the use of this combination in elderly and pretreated patients.

Adjuvant therapy for operable breast cancer with medroxyprogesterone acetate alone in postmenopausal patients or in combination with CMF in premenopausal patients.

The present paper concerns two multicenter studies on adjuvant therapy with medroxyprogesterone acetate (MAP) for operable N+ breast cancer. The patients entered the study between April 1979 and March 1986. One hundred and fifty-one premenopausal patients were randomly assigned to receive either polychemotherapy (CMF) or CMF + MAP. One hundred and thirty-eight postmenopausal patients were randomized to receive either MAP h.d. or no treatment. CMF was administered according the following schedule: cyclophosphamide mg 100/ms p.o. 1-4 days; methotrexate mg 40/ms i.v. and fluorouracil mg 600/ms i.v. 1st and 8th days. The cycle was repeated six times every 28 days. MAP was administered at 1000 mg X 2/daily p.o. for 30 days and afterwards 500 mg X 2/daily for 5 months. In the premenopausal study after a median follow-up of 36 months no difference was observed in the incidence of recurrence, site of recurrence, actuarial 5-year disease-free survival (DFS) or overall survival (OS). In the postmenopausal study a statistically significant lower number of recurrences was observed in MAP-treatment patients after a median follow-up of 37 months. The effect of MAP was limited to patients with less than or equal to 3 metastatic axillary lymph nodes. In addition, there are suggestions that only patients with ER+ tumors draw some advantage from the treatment. On the other hand, no difference exists in the OS. The treatments were substantially well tolerated. The MAP + CMF regimen induces lower vomiting compared to the CMF alone. The most frequent MAP side-effects were vaginal spotting (16%) and tremors (12%). We conclude that MAP h.d., like tamoxifen and aminoglutethimide, can improve the DFS of operable N+ breast cancer in postmenopausal patients.

Comparative phase II study of idarubicin versus doxorubicin in advanced breast cancer.

The aim of the present study is to confirm the antitumor activity of orally administered idarubicin (IDA) in patients with advanced breast cancer. Doxorubicin (ADRIA) was chosen as control treatment and the patients were randomized to receive either IDA or ADRIA according to a 2:1 ratio. Sixty-three patients, 77% of whom were pretreated with chemotherapy excluding anthracyclines, entered the study. The doses were: IDA 45 mg/m2 orally on 3 consecutive days every 28 days: ADRIA 75 (60) mg/m2 intravenously every 21 days. A complete + partial response (CR + PR) was observed in 11/37 (30%) evaluable cases treated with IDA and in 6/19 (32%) cases treated with ADRIA. If all the patients were included, the CR + PR remission rates were 27.5 and 27%, respectively. There were no significant differences as regards time to remission, duration of remission and survival. None of 10 cases who crossed over the treatments responded to the second therapy. The most frequent side effects of IDA were myelosuppression and nausea/vomiting. The only significant statistical difference between the two anthracyclines was the lower incidence of alopecia after IDA. Although there were 3 cases of cardiotoxicity after ADRIA, 2 of which severe, no case of clinical cardiotoxicity was observed after IDA. The present study confirms that orally administered IDA is an active agent in advanced breast cancer.