Preliminary results from a study conducted by Dr. D. Firat and coworkers in Ankara, Turkey, confirm that the combination of vinorelbine (Navelbine) and doxorubicin(Drug information on doxorubicin) has major antitumor activity when used as first-line therapy in advanced breast cancer. Moreover, the combination has an excellent tolerance profile and low morbidity and is easy to administer on an outpatient basis. To date, the combination has yielded an overall response rate of 62% (95% confidence interval, 46% to 78%), with complete responses in 32% of patients.
The researchers, who presented their findings at the 19th Annual San Antonio Breast Cancer Symposium, were inspired by a previous study. Other scientists had obtained a response rate of 74%, 21% of which were complete responses, in patients with advanced breast cancer with a regimen of vinorelbine, 25 mg/m² on days 1 and 8, and doxorubicin, 50 mg/m² on day 1, every 21 days. In this earlier study, responses were observed in 50% of patients with liver metastases and 68% of those with lung metastases. These data, in addition to the knowledge that fractionated doses of doxorubicin may improve tolerance without impairing efficacy, were the basis for the Turkish investigators' phase II study.
New Schedule Assessed
Their objective was to assess a new schedule of this combination designed to improve tolerance, chiefly in terms of cardiotoxicity. Both vinorelbine and doxorubicin were administered intravenously at 25 mg/m² on days 1 and 8 every 21 days, for a maximum of eight cycles (or six cycles, in cases of complete response).
Of the 37 study patients with metastatic breast cancer previously untreated by chemotherapy, 34 were evaluable for tolerance and response. Their ages ranged from 30 to 67; 97% had performance status 0 to 1; and 41% had stage IV disease at entry, 51% with predominant visceral involvement and 76% with two or more organs involved. Patients received 186 cycles of therapy (median, 6; range, 1 to 8).
At least one episode of WHO criteria grades 3 to 4 neutropenia was observed in 23.3% of patients (4.1% of cycles). The incidence of infection was very low; only one patient developed a grade 3 infection (0.5% of cycles). Significant nausea/vomiting (grades 3 to 4) was seen in 29% of patients (8% of cycles). One patient developed grade 4 constipation, and no grade 2 peripheral neuropathy was observed. Grade 3 alopecia occurred in 41% of patients. No cardiac impairment greater than grade 2 was observed. Other side effects were uncommon.