Adjuvant treatment of breast cancer patients with 1-3 positive lymph nodes: vinorelbine plus epirubicin; vinorelbine plus epirubicin sequential followed up by paclitaxel; epirubicin plus cyclophosphamide; epirubicin plus cyclophosphamide sequential followed up by paclitaxel. A phase II study.

PURPOSE: The efficacy of anthracyclin-containing adjuvant chemotherapy of node-positive breast cancer can be further improved by adding sequential paclitaxel (T). There is also clinical evidence that replacing cyclophosphamide (C) with vinorelbin (V) might further reduce toxicity. In order to assess the safety of these options, we initiated a clinical cohort study of epirubicin/cyclophoshamide and epirubicin/vinorelbine with or without sequential paclitaxel. METHOD: Patients with node-positive (1-3) breast cancer were assigned to open-label epirubicin/vinorelbine (EV), epirubicin/vino-relbine and sequential paclitaxel (EV/T), epirubicin/cyclophosphamide (EC) or epirubicin/cyclophosphamide plus sequential paclitaxel (EC/T) therapy. RESULTS: Fifty four outpatients received a total of 304 chemotherapy cycles. There were significant differences in grade III/IV anemia only between the EV/T and EC/T groups, in favor of the EC/T group (P=0.002). CONCLUSIONS: The safety of paclitaxel is not impaired when given sequentially after administration of the two anthracyclin-containing regimens. The exchange of cyclophosphamide against vinorelbine leads to deteriorating safety of the EC/T regimen.

[Dose intensified adjuvant chemotherapy in high risk breast carcinoma with 4-9 positive lymph nodes]. / Dosisintensivierte adjuvante Chemotherapie beim Hochrisikomammakarzinom mit 4-9 positiven Lymphknoten.

OBJECTIVE: Taxanes and anthracyclines represent the two most active groups of agents for the treatment of breast cancer. We evaluated this combination in patients with more than 3 positive lymph nodes in an adjuvant, dose-intensive, sequential therapy in comparison with the standard chemotherapy regimen epirubicin/cyclophosphamide in relation to toxicities. MATERIAL AND METHODS: Since 9/96 127 patients with 4-9/over 9 positive lymph nodes have been recruited from 21 participating centers in an ongoing trial. 67 patients were prospectively randomised for first-line chemotherapy to treatment group A (epirubicin 90 mg/m2-paclitaxel 175 mg/m2; 4 cycles bi-weekly, supported by G-CSF 5 micrograms/kg day 5-13 and 3 sequential cycles of CMF 600/40/600 mg/m2 at 2-weeks interval) and 60 patients to treatment group B (epirubicin 90 mg/m2-cyclophosphamide 600 mg/m2, 4 cycles tri-weekly, and 3 sequential cycles of CMF 600/40/600 mg/m2 at 3-weeks interval). RESULTS: Preliminary safety and toxicity data are evaluable for 679 cycles. Data about response rate and disease-free-survival and overall survival will be delivered later. For the hematological toxicity the main grade 3 and 4 adverse events for A vs. B were: leucopenia 9.8% vs. 8.4%, febrile neutropenia 1.6% vs. 0.8%--anemia (< 5.9 mmol/l), 0.4% vs. 0.2%--thrombopenia 0% vs. 0%. Non-hematological toxicity occurred more frequently in group A (grade 2, 3, 4):--neuropathy 4.4% vs. 0%,--nausea/emesis 27.8% vs. 19.3%,--fatigue 14.6% vs. 3.4% and mucositis 2.8% vs. 0.3%.