Docetaxel versus docetaxel alternating with gemcitabine as treatments of advanced breast cancer: final analysis of a randomised trial

Abstract

Background: Alternating administration of docetaxel and gemcitabine might result in improved time-to-treatment failure (TTF) and fewer adverse events compared with single-agent docetaxel as treatment of advanced breast cancer.Patients and methods: Women diagnosed with advanced breast cancer were randomly allocated to receive 3-weekly docetaxel (group D) or 3-weekly docetaxel alternating with 3-weekly gemcitabine (group D/G) until treatment failure as first-line chemotherapy. The primary end point was TTF.Results: Two hundred and thirty-seven subjects were assigned to treatment (group D, 115; group D/G, 122). The median TTF was 5.6 and 6.2 months in groups D and D/G, respectively (hazard ratio 0.85, 95% confidence interval 0.63–1.16; P = 0.31). There was no significant difference in time-to-disease progression, survival, and response rate between the groups. When adverse events were evaluated for the worst toxicity encountered during treatment, there was little difference between the groups, but when they were assessed per cycle, alternating treatment was associated with fewer severe (grade 3 or 4) adverse effects (P = 0.013), and the difference was highly significant for cycles when gemcitabine was administered in group D/G (P < 0.001).Conclusion: The alternating regimen was associated with a similar TTF as single-agent docetaxel but with fewer adverse effects during gemcitabine cycles.

Efficacy of gemcitabine-based chemotherapy in metastatic breast cancer: a meta-analysis of randomized controlled trials

“…Based on the results of this study, both gemcitabinebased and gemcitabine-free chemotherapy are possible Feher 12 Zielinski 13 Martín 14 Albain 15 Joensuu 17 Nielsen 18 Pallis 20 Test for overall effect: Z = 4.25 (P < 0.0001) Heterogeneity: Chi 2 = 9.32, df = 5 (P = 0.10); I 2 = 46% options for patients with metastatic breast cancer. However, for patients requiring a rapid and significant response for symptom control or life-threatening disease, gemcitabine-based doublets might be a more reasonable choice.…”

“…Four trials were excluded [8][9][10][11] , namely, a phase III trial using a three-arm design, two phase III trials without a gemcitabine-free control arm and a phase II trial without sufficient data. A total of nine trials met the inclusion criteria in this metaanalysis [12][13][14][15][16][17][18][19][20] , from which 2651 patients were included in the assessment for overall response and toxicity. Eight of these trials were assessed for overall survival, and seven for time to progression.…”

“…Overall, seven trials had Jadad scores of 3 and two of 2. The quality was high in seven phase III studies [12][13][14][15][16][17][18] (Jadad score 3). Two trials were of low quality (Jadad score 2) including one phase II trial 19 and one phase III trial 20 .…”

“…Given that different chemotherapeutics are associated with multiple adverse events, we compared only grade 3 and 4 hematologic toxicity adverse effects between gemcitabine-free and Feher 12 Zielinski 13 Martín 14 Albain 15 Chan 16 Joensuu 17 Nielsen 18 Brufsky 19 Pallis 20 Test for overall effect: Z = 1.83 (P = 0.07) Heterogeneity: Chi 2 = 7.14, df = 8 (P = 0.52); I 2 = 0% Zielinski 13 Feher 12 Martín 14 Albain 15 Joensuu 17 Chan 16 Nielsen 18 Brufsky 19 Pallis 20 Test for overall effect: Z = 0.13 (P = 0.90) Heterogeneity: Tau For personal use only.…”

“…Specifically, higher frequencies of anemia (HR 2.02, 95% CI 1.35-3.02; P ¼ 0.006), neutropenia (HR 2.33, 95% CI 1.37-3.63; P ¼ 0.01) and thrombocytopenia (HR 8.31, 95% CI 5.00-13.82; P50.0001) were observed in the gemcitabine-based arm ( Figure 11). 12 Zielinski 13 Martín 14 Albain 15 Joensuu 17 Chan 16 Brufsky 19 Pallis 20 Nielsen 18 Test for overall effect: Z = 0.71 (P = 0.48) Heterogeneity: Tau 2 = 0.07; Chi 2 = 51. 16 Feher 12 Martín 14 Albain 15 Chan 16 Joensuu 17 Pallis 20 Nielsen 18 Brufsky 19 Test for overall effect: Z = 1.05 (P = 0.29) Heterogeneity: Chi 2 = 6.72, df = 6 (P = 0.035); I 2 = 11% 12 Martín 14 Albain 15 Chan 16 Joensuu 17 Nielsen 18 Brufsky 19 Pallis 20 Test for overall effect: Z = 0.53 (P = 0.60) Heterogeneity: Tau 2 = 0.04; Chi 2 = 18.08, df = 7 (P = 0.01); I 2 = 61% Subgroup: gemcitabine-based doublet versus single agent…”