Phase II study of weekly vinorelbine and 24-h infusion of high-dose 5-fluorouracil plus leucovorin as first-line treatment of advanced breast cancer

We prospectively investigated the efficacy and safety of combining weekly vinorelbine (VNB) with weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) and leucovorin (LV) in the treatment of patients with advanced breast cancer (ABC). Vinorelbine 25 mg m−2 30-min intravenous infusion, and high-dose 5-FU 2600 mg m−2 plus LV 300 mg m−2 24-h intravenous infusion (HDFL regimen) were given on days 1 and 8 every 3 weeks. Between June 1999 and April 2003, 40 patients with histologically confirmed recurrent or metastatic breast cancer were enrolled with a median age of 49 years (range: 36–68). A total of 25 patients had recurrent ABC, and 15 patients had primary metastatic diseases. The overall response rate for the intent-to-treat group was 70.0% (95% CI: 54–84%) with eight complete responses and 20 partial responses. All 40 patients were evaluated for survival and toxicities. Among a total of 316 cycles of VNB–HDFL given (average: 7.9: range: 4–14 cycles per patient), the main toxicity was Gr3/4 leucopenia and Gr3/4 neutropenia in 57 (18.0%) and 120 (38.0%) cycles, respectively. Gr1/2 infection and Gr1/2 stomatitis were noted in five (1.6%) and 59 (18.7%) cycles, respectively. None of the patients developed Gr3/4 stomatitis or Gr3/4 infection. Gr2/3 and Gr1 hand–foot syndrome was noted in two (5.0%) and 23 (57.5%) patients, respectively. Gr1 sensory neuropathy developed in three patients. The median time to progression was 8.0 months (range: 3–25.5 months), and the median overall survival was 25.0 months with a follow-up of 5.5 to 45+ months. This VNB–HDFL regimen is a highly active yet well-tolerated first-line treatment for ABC

Effects of adjuvant tamoxifen and of cytotoxic therapy on mortality in early breast cancer. An overview of 61 randomized trials among 28,896 women. Early Breast Cancer Trialists' Collaborative Group.

We sought information worldwide on mortality according to assigned treatment in all randomized trials that began before 1985 of adjuvant tamoxifen or cytotoxic therapy for early breast cancer (with or without regional lymph-node involvement). Coverage was reasonably complete for most countries. In 28 trials of tamoxifen nearly 4000 of 16,513 women had died, and in 40 chemotherapy trials slightly more than 4000 of 13,442 women had died. The 8106 deaths were approximately evenly distributed over years 1, 2, 3, 4, and 5+ of follow-up, with little useful information beyond year 5. Systematic overviews of the results of these trials demonstrated reductions in mortality due to treatment that were significant when tamoxifen was compared with no tamoxifen (P less than 0.0001), any chemotherapy with no chemotherapy (P = 0.003), and polychemotherapy with single-agent chemotherapy (P = 0.001). In tamoxifen trials, there was a clear reduction in mortality only among women 50 or older, for whom assignment to tamoxifen reduced the annual odds of death during the first five years by about one fifth. In chemotherapy trials there was a clear reduction only among women under 50, for whom assignment to polychemotherapy reduced the annual odds of death during the first five years by about one quarter. Direct comparisons showed that combination chemotherapy was significantly more effective than single-agent therapy, but suggested that administration of chemotherapy for 8 to 24 months may offer no survival advantage over administration of the same chemotherapy for 4 to 6 months. Because it involved several thousand women, this overview was able to demonstrate particularly clearly that both tamoxifen and cytotoxic therapy can reduce five-year mortality