This Article Full Text Full Text (PDF) eLetters: Submit a response to this article Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services E-mail this article link to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Hochster, H. S. Articles by White, R. Search for Related Content PubMed PubMed Citation Articles by Hochster, H. S. Articles by White, R.

Activity and Safety of Vinorelbine Combined with Doxorubicin or Fluorouracil as First-Line Therapy in Advanced Breast Cancer: A Stratified Phase II Study

^a New York University Medical Center, New York, New York, USA; ^b Comprehensive Cancer Research Group Inc., Miami, Florida, USA; ^c Glaxo Wellcome Inc., Research Triangle Park, North Carolina, USA

Correspondence: Howard S. Hochster, M.D., New York University Medical Center, 160 East 32nd Street, 2nd Floor, New York, NY 10016-6004, USA. Telephone: 212-652-1912, Fax: 212-652-1901; e-mail: howard.hochster{at}med.nyu.edu

Purpose. To evaluate the efficacy and safety of vinorelbine combined with doxorubicin or continuous infusion of fluorouracil as initial therapy for advanced breast cancer.

Subjects and Methods. A total of 118 women who had not received chemotherapy for advanced breast cancer were enrolled and included in the intent-to-treat analysis. Subjects were stratified into two treatment groups. If subjects were candidates for anthracycline therapy, they received doxorubicin 50 mg/m² on day 1 and vinorelbine 25 mg/m² on days 1 and 8 (n = 62). If subjects had received adjuvant anthracycline therapy or had cardiac disease, they received fluorouracil 750 mg/m²/day by continuous infusion on days 1 through 5 and vinorelbine 30 mg/m² on days 1 and 5 (n = 56). The regimens were repeated every 21 days until evidence of progression of disease or severe toxicity.

Results. For doxorubicin and vinorelbine, the objective response rate was 55% (95% confidence interval [CI]: 42% to 68%), median time to disease progression was 34 weeks, median time to treatment failure was 32 weeks, and median survival was 92 weeks (95% CI: 72 to 128 weeks). For fluorouracil and vinorelbine, the objective response rate was 45% (95% CI: 31% to 59%), median time to disease progression was 32 weeks, median time to treatment failure was 30 weeks, and median survival was 53 weeks (95% CI: 47 to 64 weeks). The most common adverse event was grade 3 or 4 granulocytopenia, which occurred in 95% of subjects in the doxorubicin-vinorelbine group and in 88% of those in the fluorouracil-vinorelbine group. The most common nonhematologic adverse event was grade 3 or 4 stomatitis, which occurred in 9% and 32% of subjects in the two groups, respectively.

Conclusion. Both vinorelbine-containing regimens appear to offer useful options as initial therapy for advanced breast cancer. Both regimens were active, and any efficacy differences between the two may have been related to differences in prognosis for the anthracycline-pretreated group (i.e., selection for prior aggressive adjuvant therapy) and or comorbid cardiac conditions. Both regimens were associated with predictable but manageable toxicity, but a lower dose of fluorouracil (e.g., 600 mg/m²/day) should be used to reduce the risk of stomatitis.

Key Words. Vinorelbine • Doxorubicin • Fluorouracil • Advanced breast cancer • Combination chemotherapy