Table 6. Standard Adjuvant Chemotherapy Regimens for Stage I, II, IIIA, and Operable IIICHER2/neuNon-Overexpressing Breast Cancer continued...
A U.S. Intergroup trial (CLB-9741) compared, in a 2 × 2 factorial design, the use of adriamycin, cyclophosphamide, and paclitaxel concurrently (adriamycin and cyclophosphamide followed by paclitaxel) versus sequentially (adriamycin followed by paclitaxel followed by cyclophosphamide), given every 3 weeks or every 2 weeks with filgrastim, in 2,005 node-positive premenopausal and postmenopausal patients. At a median follow-up of 68 months, dose-dense treatment improved the primary end point, DFS in all patient population (HR, 0.80; P =.018) but not OS (HR, 0.85; P =.12). There was no interaction between density and sequence. Severe neutropenia was less frequent in patients who received the dose-dense regimens.[183,184] Grade 2 anemia (hemoglobin <10g/dL) was more frequent in the adriamycin and cyclophosphamide followed by paclitaxel every 2 weeks' arm (P < .001). At cycle five, this same arm had the lowest nadir hemoglobin of 10.7 g/dL, 0.9 g/dL lower than the other arms. Also, epoetin alpha use was highest in this arm compared with the three other arms (P = .013). In conclusion, dose-dense adriamycin and cyclophosphamide followed by paclitaxel every 14 days in C2 was associated with a greater incidence of moderate anemia, higher use of epoetin alpha, and more red cell transfusions than the other arms.[Level of evidence: 1iiA]
Several clinical trials (including EST-2190) have tested high-dose chemotherapy with bone marrow transplant (BMT) or stem cell support in women with more than ten positive lymph nodes and in women with four to nine positive lymph nodes.[186,187,188,189,190,191,192,193] A prospective, randomized trial of 403 patients testing the use of two tandem high-dose chemotherapy courses demonstrated a statistically significant (P = .02) difference in 5-year survival (75% vs. 70%) with a 49-month median follow-up.[Level of evidence: 1iiA] The remaining trials comparing conventional chemotherapy to high-dose chemotherapy with BMT or stem cell support in high-risk patients in the adjuvant setting indicated no OS or EFS benefit from the high-dose chemotherapy with BMT or stem cell support.[186,187,188,189,190,191,193,194,195][Level of evidence: 1iiA] The information to date does not support the use of high-dose chemotherapy outside the context of a randomized clinical trial.
Also, a systematic review of nine randomized, controlled trials comparing the effectiveness of high-dose chemotherapy and autograft with conventional chemotherapy for women with early poor prognosis breast cancer was performed. In total 1,758 women were randomly assigned to receive high-dose chemotherapy with autograft, and 1,767 women were randomly assigned to receive conventional chemotherapy. There were 48 noncancer-related deaths on the high dose arm and four on the conventional dose arm (RR, 7.74; 95% CI, 3.43–17.50). There was no statistically significant difference in OS between women who received high-dose chemotherapy with autograft and women who received conventional chemotherapy, either at 3 years (RR = 1.02; 95% CI, 0.98–1.06), or at 5 years (RR, 0.98; 95% CI, 0.93–1.05). There was a statistically significant benefit in EFS at 3 years for the group who received high-dose chemotherapy (RR, 1.11; 95% CI, 1.05–1.18). However, this significance was lost at 5 years (RR, 1.00; 95% CI, 0.92–1.08).