Vinorelbine/Doxorubicin Combination Demonstrates Major Antitumor Activity in Advanced Breast Carcinoma

April 1, 1997

Preliminary results from a study conducted by Dr. D. Firat and coworkers in Ankara, Turkey, confirm that the combination of vinorelbine (Navelbine) and doxorubicin has major antitumor activity when used as first-line therapy in advanced breast

Preliminary results from a study conducted by Dr. D. Firat and coworkersin Ankara, Turkey, confirm that the combination of vinorelbine (Navelbine)and doxorubicin has major antitumor activity when used as first-line therapyin advanced breast cancer. Moreover, the combination has an excellent toleranceprofile 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 SanAntonio Breast Cancer Symposium, were inspired by a previous study. Otherscientists had obtained a response rate of 74%, 21% of which were completeresponses, 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% ofpatients with liver metastases and 68% of those with lung metastases. Thesedata, in addition to the knowledge that fractionated doses of doxorubicinmay improve tolerance without impairing efficacy, were the basis for theTurkish investigators' phase II study.

New Schedule Assessed

Their objective was to assess a new schedule of this combination designedto improve tolerance, chiefly in terms of cardiotoxicity. Both vinorelbineand doxorubicin were administered intravenously at 25 mg/m² on days1 and 8 every 21 days, for a maximum of eight cycles (or six cycles, incases of complete response).

Of the 37 study patients with metastatic breast cancer previously untreatedby chemotherapy, 34 were evaluable for tolerance and response. Their agesranged from 30 to 67; 97% had performance status 0 to 1; and 41% had stageIV 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 observedin 23.3% of patients (4.1% of cycles). The incidence of infection was verylow; only one patient developed a grade 3 infection (0.5% of cycles). Significantnausea/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 neuropathywas observed. Grade 3 alopecia occurred in 41% of patients. No cardiacimpairment greater than grade 2 was observed. Other side effects were uncommon.