Dose-intensive epirubicin-based chemotherapy is superior to an intensive intravenous cyclophosphamide, methotrexate, and fluorouracil regimen in metastatic breast cancer: a randomized multinational study.

PURPOSE: To determine the relative efficacy of a cyclophosphamide epirubicin and fluorouracil (CEF) regimen compared with an intravenous (IV) cyclophosphamide, methotrexate, and fluorouracil (CMF) combination in metastatic breast cancer. PATIENTS AND METHODS: Patients were randomized to receive either CEF (cyclophosphamide 400 mg/m(2) IV, epirubicin 50 mg/m(2) IV, and fluorouracil 500 mg/m(2) IV on days 1 and 8), or CMF (cyclophosphamide 500 mg/m(2) IV, methotrexate 40 mg/m(2) IV, and fluorouracil 600 mg/m(2) IV on days 1 and 8). Treatment was given in 3- to 4-week cycles for a total of six to nine cycles. RESULTS: A total of 460 patients (223 CEF and 237 CMF) were randomized. Overall response rate was superior for CEF than CMF in all randomized patients (57% v 46%, respectively; P =.01) and in the assessable subset (66% v 52%, respectively; P =.005). With a median follow-up of more than 20 months, time to progression (TTP) was significantly longer with CEF than CMF (median 8.9 v 6.3 months, respectively; P =.0064), as was time to treatment failure (TTF) (median 6.2 v 5.0 months, respectively; P =.01). Significant survival differences were not observed between CEF and CMF (median 20.1 v 18.2 months, respectively; P =.23). Granulocytopenia and infections were similar in both arms. Grade 3/4 nausea/vomiting and alopecia were more frequent with CEF, whereas diarrhea was more frequent with CMF. Cardiac toxicity, primarily asymptomatic, required withdrawal from study of 15 patients on CEF (7%) and one patient on CMF. CONCLUSION: This CEF regimen safely provides significantly better tumor control than CMF, manifest as a higher response rate, and longer TTP and TTF, but not survival, when used as first-line chemotherapy for metastatic breast cancer.

Tolciclate in the local treatment of skin candidiases: a double-blind controlled multiclinic trial versus clotrimazole.

A controlled double-blind multiclinic trial comparing the activity and tolerability of tolciclate and clotrimazole on skin candidiasis was carried out in twenty-seven dermatological departments throughout Italy. Two hundred and seventy-eight patients were admitted to the trial. Tolciclate and clotrimazole 1% cream and lotion were applied twice a day for a mean time of about 3 weeks. Efficacy was evaluated weekly during the treatment both by clinical and mycological (culture) examinations. Culture baseline findings were positive for Candida sp in about 72% of cases; C. albicans was the most frequent species (41.5%) but also C. krusei and C. stellatoidea were isolated in a high percentage of cases. Tolciclate induced clinical cure or improvement in 89.7% of cases, mycological conversion in 73.6% with an overall efficacy (clinical + mycological) in 72.2%. Clotrimazole gave comparable results with, respectively, 95.7% of clinical cure or improvement, 75.3% of culture conversion and 77.6% of overall efficacy. The differences were small and statistically not significant. Tolerability was good and similar in both experimental groups.

Multicentre clinical study with tolciclate in the local treatment of skin mycoses in 1083 patients.

A multicentre clinical trial with tolciclate was carried out in Italy on 1083 patients suffering from skin mycoses (tinea corporis, tinea cruris, tinea pedis, tinea manuum and pityriasis versicolor). Both preparations (1% cream and lotion) showed a good activity evaluated weekly by clinical examinations and mycological assessments, i.e. culture for tineas and microscopy for pityriasis versicolor. Favourable clinical results ranged from 83% to 97% according to diagnoses. Cultural or microscopic conversions obtained in a mean time of about 2 weeks varied from 70% to 91%. Mycological relapses a month after the end of treatment were seen in 6.5% of cases examined. Adverse reactions were observed in 5.6% of patients but the treatment was discontinued only in 2.6%.

Doubling epirubicin dose intensity (100 mg/m2 versus 50 mg/m2) in the FEC regimen significantly increases response rates. An international randomised phase III study in metastatic breast cancer. The Epirubicin High Dose (HEPI 010) Study Group.

PURPOSE: A phase III study was performed in patients with metastatic breast cancer (MBC) to evaluate the effect on response rate and survival of a doubling of the epirubicin dose intensity. PATIENTS AND METHODS: Four hundred fifty-six patients were randomised to receive either epirubicin 100 mg/m2 or 50 mg/m2 in combination with 5-FU (500 mg/m2) and cyclophosphamide (500 mg/m2) (FEC 100 vs. FEC 50) i.v., every 21 days for a maximum of six cycles (eight in case of CR). RESULTS: Of 456 patients, 390 were evaluable for efficacy. Objective response (CR + PR) was seen in 57% (FEC 100) vs. 41% (FEC 50) of the evaluable patients (P = 0.003). The CR rate was higher in the FEC 100 arm (12% vs. 7%, P = 0.07). FEC 100 produced significantly higher response rates in patients with visceral localisation (50% vs. 34%, P = 0.011) and in patients with more than two metastatic organ sites (64% vs. 37%, P = 0.001). Median time to progression (7.6 vs. 7 months) and overall survival (18 months vs. 17 months) were similar. Myelosuppression was the principal toxic effect, with grade IV neutropenia observed in 57% of the patients treated with FEC 100 vs. 9% of those on FEC 50. Grade IV infection or febrile neutropenia were observed in 8% (FEC 100) vs. 0.4% (FEC 50), but the incidence of septic death was the same in the two arms (two patients each). Cardiac toxicity was similar in the two treatment groups, with 5% vs. 3% of the patients taken off study due to cardiac events, primarily due to a decline in LVEF. Only three patients (two in FEC 100) experienced congestive heart failure. CONCLUSION: This trial shows that FEC with epirubicin at 100 mg/m2 can be administered for repeated cycles without bone marrow support with increased, though acceptable, toxicity and with a significant increase of antitumor effect (especially in visceral and/or high-burden disease), but no increased survival.